Mining the pharmacogenomics literature—a survey of the state of the art
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paper_title: Recent progress in automatically extracting information from the pharmacogenomic literature.

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The biomedical literature holds our understanding of pharmacogenomics, but it is dispersed across many journals. In order to integrate our knowledge, connect important facts across publications and generate new hypotheses we must organize and encode the contents of the literature. By creating databases of structured pharmocogenomic knowledge, we can make the value of the literature much greater than the sum of the individual reports. We can, for example, generate candidate gene lists or interpret surprising hits in genome-wide association studies. Text mining automatically adds structure to the unstructured knowledge embedded in millions of publications, and recent years have seen a surge in work on biomedical text mining, some specific to pharmacogenomics literature. These methods enable extraction of specific types of information and can also provide answers to general, systemic queries. In this article, we describe the main tasks of text mining in the context of pharmacogenomics, summarize recent applications and anticipate the next phase of text mining applications.
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paper_title: The text mining handbook: advanced approaches in analyzing unstructured data

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Providing an in-depth examination of core text mining and link detection algorithms and operations, this text examines advanced pre-processing techniques, knowledge representation considerations, and visualization approaches.
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paper_title: Biomedical Text Mining and Its Applications

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This tutorial is intended for biologists and computational biologists interested in adding text mining tools to their bioinformatics toolbox. As an illustrative example, the tutorial examines the relationship between progressive multifocal leukoencephalopathy (PML) and antibodies. Recent cases of PML have been associated to the administration of some monoclonal antibodies such as efalizumab [1]. Those interested in a further introduction to text mining may also want to read other reviews [2]–[4]. ::: ::: Understanding large amounts of text with the aid of a computer is harder than simply equipping a computer with a grammar and a dictionary. A computer, like a human, needs certain specialized knowledge in order to understand text. The scientific field that is dedicated to train computers with the right knowledge for this task (among other tasks) is called natural language processing (NLP). Biomedical text mining (henceforth, text mining) is the subfield that deals with text that comes from biology, medicine, and chemistry (henceforth, biomedical text). Another popular name is BioNLP, which some practitioners use as synonymous with text mining. ::: ::: Biomedical text is not a homogeneous realm [5]. Medical records are written differently from scientific articles, sequence annotations, or public health guidelines. Moreover, local dialects are not uncommon [6]. For example, medical centers develop their own jargons and laboratories create their idiosyncratic protein nomenclatures. This variability means, in practice, that text mining applications are tailored to specific types of text. In particular, for reasons of availability and cost, many are designed for scientific abstracts in English from Medline.
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paper_title: Pharmacogenomics: The Search for Individualized Therapies

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Preface.List of Contributors.Color Plates.Introduction to Pharmacogenomics: Promises, Opportunities, and Limitations (U. Meyer). The Human Genome (S. Broder, et al.). Turning SNPs into Useful Makers of Drug Response (J. McCarthy). Association Studies in Pharmacogenomics (L. Essioux, et al.). Genomics Application that Facilitate the Understanding of Drug Action and Toxicity (L. Furness). The Role of Pharmacogenetics in Drug Discovery and Therapeutics (K. Lindpaintner). Pharmacogenomics and Drug Design (P. Dean, et al.). The Pharmacogenomics of Human P--Glycoprotein (M. Fromm & M. Eichelbaum). Pharmacogenomics of Drug Transporters (R. Tirona & R. Kim). Pharmacogenomics of Asthma Treatment (L. Palmer, et al.). Endothelial Cells are Targets for Hydroxy Urea: Relevance to the Current Therapeutic Strategy in Sickle Cell Disease (C. Lapoumeroulie, et al.). Pharmacogenomics and Complex Cardiovascular Disease -- Clinical Studies in Candidate Genes (B. Winkelmann, et al.). Pharmacogenomics of Lipid--Lowering Agents (M. Hoffmann, et al.). Pharmacogenomics of Chemotherapeutic Agents in Cancer Treatment (F. Innocenti, et al.). Pharmacogenomics of the Blood--Brain Barrier (J.--M. Scherrmann). Pharmacogenomics and the Treatment of Neurological Disease (D. Goldstein, et al.). Pharmacogenomics of Neurodegenerative Diseases: Examples and Perspectives (P. Hantraye, et al.). Psychiatric Pharmacogenetics: Prediction of Treatment Outcomes in Schizophrenia (M. Masellis, et al.). Pharmacogenomics of Major Depression and Antidepressant Treatment (M.--L. Wong, et al.). Pharmacogenomics of Bipolar Disorder (H. Manji, et al.). Pharmacogenomics of Alcoholism (T. Hurley, et al.). Pharmacogenomics of Tobacco Addiction (E. Johnstone, et al.). Pharmacogenomics of Opioid Systems (T. Reisine). Ethnicity and Pharmacogenomics (H. McLeod & M. Ameyaw). Pharmacogenomics: Ensuring Equity Regarding Drugs Based on Genetic Difference (P. Epps & M. Rothstein). Translation of Vascular Proteomics into Individualized Therapeutics (R. Pasqualini & W. Arap). Glossary of Key Terms in Molecular Genetics of Pharmacogenomics (B. Winkelmann, et al.). Index.
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paper_title: What makes a gene name ? Named entity recognition in the biomedical literature

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The recognition of biomedical concepts in natural text (named entity recognition, NER) is a key technology for automatic or semi-automatic analysis of textual resources. Precise NER tools are a prerequisite for many applications working on text, such as information retrieval, information extraction or document classification. Over the past years, the problem has achieved considerable attention in the bioinformatics community and experience has shown that NER in the life sciences is a rather difficult problem. Several systems and algorithms have been devised and implemented. In this paper, the problems and resources in NER research are described, the principal algorithms underlying most systems sketched, and the current state-ofthe-art in the field surveyed.
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paper_title: The BioScope corpus: annotation for negation, uncertainty and their scope in biomedical texts

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This article reports on a corpus annotation project that has produced a freely available resource for research on handling negation and uncertainty in biomedical texts (we call this corpus the BioScope corpus). The corpus consists of three parts, namely medical free texts, biological full papers and biological scientific abstracts. The dataset contains annotations at the token level for negative and speculative keywords and at the sentence level for their linguistic scope. The annotation process was carried out by two independent linguist annotators and a chief annotator -- also responsible for setting up the annotation guidelines -- who resolved cases where the annotators disagreed. We will report our statistics on corpus size, ambiguity levels and the consistency of annotations.
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paper_title: Extracting information from textual documents in the electronic health record: a review of recent research.

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Objectives: We examine recent published research on the extraction of information from textual documents in the Electronic Health Record (EHR). Methods: Literature review of the research published after 1995, based on PubMed, conference proceedings, and the ACM Digital Library, as well as on relevant publications referenced in papers already included. Results: 174 publications were selected and are discussed in this review in terms of methods used, pre-processing of textual documents, contextual features detection and analysis, extraction of information in general, extraction of codes and of information for decision-support and enrichment of the EHR, information extraction for surveillance, research, automated terminology management, and data mining, and de-identification of clinical text. Conclusions: Performance of information extraction systems with clinical text has improved since the last systematic review in 1995, but they are still rarely applied outside of the laboratory they have been developed in. Competitive challenges for information extraction from clinical text, along with the availability of annotated clinical text corpora, and further improvements in system performance are important factors to stimulate advances in this field and to increase the acceptance and usage of these systems in concrete clinical and biomedical research contexts. Cli
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paper_title: Text Mining: Predictive Methods for Analyzing Unstructured Information

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The growth of the web can be seen as an expanding public digital library collection. Online digital information extends far beyond the web and its publicly available information. Huge amounts of information are private and are of interest to local communities, such as the records of customers of a business. This information is overwhelmingly text and has its record-keeping purpose, but an automated analysis might be desirable to find patterns in the stored records. Analogous to this data mining is text mining, which also finds patterns and trends in information samples but which does so with far less structured--though with greater immediate utility for users--ingredients. This book focuses on the concepts and methods needed to expand horizons beyond structured, numeric data to automated mining of text samples. It introduces the new world of text mining and examines proven methods for various critical text-mining tasks, such as automated document indexing and information retrieval and search. New research areas are explored, such as information extraction and document summarization, that rely on evolving text-mining techniques.
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paper_title: Overview of BioNLP’09 Shared Task on Event Extraction

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The paper presents the design and implementation of the BioNLP'09 Shared Task, and reports the final results with analysis. The shared task consists of three sub-tasks, each of which addresses bio-molecular event extraction at a different level of specificity. The data was developed based on the GENIA event corpus. The shared task was run over 12 weeks, drawing initial interest from 42 teams. Of these teams, 24 submitted final results. The evaluation results are encouraging, indicating that state-of-the-art performance is approaching a practically applicable level and revealing some remaining challenges.
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paper_title: Mining the Gene Wiki for functional genomic knowledge

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BackgroundOntology-based gene annotations are important tools for organizing and analyzing genome-scale biological data. Collecting these annotations is a valuable but costly endeavor. The Gene Wiki makes use of Wikipedia as a low-cost, mass-collaborative platform for assembling text-based gene annotations. The Gene Wiki is comprised of more than 10,000 review articles, each describing one human gene. The goal of this study is to define and assess a computational strategy for translating the text of Gene Wiki articles into ontology-based gene annotations. We specifically explore the generation of structured annotations using the Gene Ontology and the Human Disease Ontology.ResultsOur system produced 2,983 candidate gene annotations using the Disease Ontology and 11,022 candidate annotations using the Gene Ontology from the text of the Gene Wiki. Based on manual evaluations and comparisons to reference annotation sets, we estimate a precision of 90-93% for the Disease Ontology annotations and 48-64% for the Gene Ontology annotations. We further demonstrate that this data set can systematically improve the results from gene set enrichment analyses.ConclusionsThe Gene Wiki is a rapidly growing corpus of text focused on human gene function. Here, we demonstrate that the Gene Wiki can be a powerful resource for generating ontology-based gene annotations. These annotations can be used immediately to improve workflows for building curated gene annotation databases and knowledge-based statistical analyses.
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paper_title: Detecting Speculations and their Scopes in Scientific Text

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Distinguishing speculative statements from factual ones is important for most biomedical text mining applications. We introduce an approach which is based on solving two sub-problems to identify speculative sentence fragments. The first sub-problem is identifying the speculation keywords in the sentences and the second one is resolving their linguistic scopes. We formulate the first sub-problem as a supervised classification task, where we classify the potential keywords as real speculation keywords or not by using a diverse set of linguistic features that represent the contexts of the keywords. After detecting the actual speculation keywords, we use the syntactic structures of the sentences to determine their scopes.
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paper_title: Analysis of Biological Processes and Diseases Using Text Mining Approaches

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A number of biomedical text mining systems have been developed to extract biologically relevant information directly from the literature, complementing bioinformatics methods in the analysis of experimentally generated data. We provide a short overview of the general characteristics of natural language data, existing biomedical literature databases, and lexical resources relevant in the context of biomedical text mining. A selected number of practically useful systems are introduced together with the type of user queries supported and the results they generate. The extraction of biological relationships, such as protein–protein interactions as well as metabolic and signaling pathways using information extraction systems, will be discussed through example cases of cancer-relevant proteins. Basic strategies for detecting associations of genes to diseases together with literature mining of mutations, SNPs, and epigenetic information (methylation) are described. We provide an overview of disease-centric and gene-centric literature mining methods for linking genes to phenotypic and genotypic aspects. Moreover, we discuss recent efforts for finding biomarkers through text mining and for gene list analysis and prioritization. Some relevant issues for implementing a customized biomedical text mining system will be pointed out. To demonstrate the usefulness of literature mining for the molecular oncology domain, we implemented two cancer-related applications. The first tool consists of a literature mining system for retrieving human mutations together with supporting articles. Specific gene mutations are linked to a set of predefined cancer types. The second application consists of a text categorization system supporting breast cancerspecific literature search and document-based breast cancer gene ranking. Future trends in text mining emphasize the importance of community efforts such as the BioCreative challenge for the development and integration of multiple systems into a common platform provided by the BioCreative Metaserver.
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paper_title: Recognizing speculative language in biomedical research articles: a linguistically motivated perspective

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BackgroundDue to the nature of scientific methodology, research articles are rich in speculative and tentative statements, also known as hedges. We explore a linguistically motivated approach to the problem of recognizing such language in biomedical research articles. Our approach draws on prior linguistic work as well as existing lexical resources to create a dictionary of hedging cues and extends it by introducing syntactic patterns.Furthermore, recognizing that hedging cues differ in speculative strength, we assign them weights in two ways: automatically using the information gain (IG) measure and semi-automatically based on their types and centrality to hedging. Weights of hedging cues are used to determine the speculative strength of sentences.ResultsWe test our system on two publicly available hedging datasets. On the fruit-fly dataset, we achieve a precision-recall breakeven point (BEP) of 0.85 using the semi-automatic weighting scheme and a lower BEP of 0.80 with the information gain weighting scheme. These results are competitive with the previously reported best results (BEP of 0.85). On the BMC dataset, using semi-automatic weighting yields a BEP of 0.82, a statistically significant improvement (p <0.01) over the previously reported best result (BEP of 0.76), while information gain weighting yields a BEP of 0.70.ConclusionOur results demonstrate that speculative language can be recognized successfully with a linguistically motivated approach and confirms that selection of hedging devices affects the speculative strength of the sentence, which can be captured reasonably by weighting the hedging cues. The improvement obtained on the BMC dataset with a semi-automatic weighting scheme indicates that our linguistically oriented approach is more portable than the machine-learning based approaches. Lower performance obtained with the information gain weighting scheme suggests that this method may benefit from a larger, manually annotated corpus for automatically inducing the weights.
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paper_title: Beyond Accuracy, F-Score and ROC: A Family of Discriminant Measures for Performance Evaluation

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Different evaluation measures assess different characteristics of machine learning algorithms. The empirical evaluation of algorithms and classifiers is a matter of on-going debate among researchers. Most measures in use today focus on a classifier's ability to identify classes correctly. We note other useful properties, such as failure avoidance or class discrimination, and we suggest measures to evaluate such properties. These measures – Youden's index, likelihood, Discriminant power – are used in medical diagnosis. We show that they are interrelated, and we apply them to a case study from the field of electronic negotiations. We also list other learning problems which may benefit from the application of these measures.
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paper_title: Evaluation of text-mining systems for biology: overview of the Second BioCreative community challenge

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Background:Genome sciences have experienced an increasing demand for efficient text-processing tools that can extract biologically relevant information from the growing amount of published literature. In response, a range of text-mining and information-extraction tools have recently been developed specifically for the biological domain. Such tools are only useful if they are designed to meet real-life tasks and if their performance can be estimated and compared. The BioCreative challenge (Critical Assessment of Information Extraction in Biology) consists of a collaborative initiative to provide a common evaluation framework for monitoring and assessing the state-of-the-art of text-mining systems applied to biologically relevant problems.Results:The Second BioCreative assessment (2006 to 2007) attracted 44 teams from 13 countries worldwide, with the aim of evaluating current information-extraction/text-mining technologies developed for one or more of the three tasks defined for this challenge evaluation. These tasks included the recognition of gene mentions in abstracts (gene mention task); the extraction of a list of unique identifiers for human genes mentioned in abstracts (gene normalization task); and finally the extraction of physical protein-protein interaction annotation-relevant information (protein-protein interaction task). The 'gold standard' data used for evaluating submissions for the third task was provided by the interaction databases MINT (Molecular Interaction Database) and IntAct.Conclusion:The Second BioCreative assessment almost doubled the number of participants for each individual task when compared with the first BioCreative assessment. An overall improvement in terms of balanced precision and recall was observed for the best submissions for the gene mention (F score 0.87); for the gene normalization task, the best results were comparable (F score 0.81) compared with results obtained for similar tasks posed at the first BioCreative challenge. In case of the protein-protein interaction task, the importance and difficulties of experimentally confirmed annotation extraction from full-text articles were explored, yielding different results depending on the step of the annotation extraction workflow. A common characteristic observed in all three tasks was that the combination of system outputs could yield better results than any single system. Finally, the development of the first text-mining meta-server was promoted within the context of this community challenge.
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paper_title: High-performance gene name normalization with GeNo

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Motivation: The recognition and normalization of textual mentions of gene and protein names is both particularly important and challenging. Its importance lies in the fact that they constitute the crucial conceptual entities in biomedicine. Their recognition and normalization remains a challenging task because of widespread gene name ambiguities within species, across species, with common English words and with medical sublanguage terms. ::: ::: Results: We present GeNo, a highly competitive system for gene name normalization, which obtains an F-measure performance of 86.4% (precision: 87.8%, recall: 85.0%) on the BioCreAtIvE-II test set, thus being on a par with the best system on that task. Our system tackles the complex gene normalization problem by employing a carefully crafted suite of symbolic and statistical methods, and by fully relying on publicly available software and data resources, including extensive background knowledge based on semantic profiling. A major goal of our work is to present GeNo's architecture in a lucid and perspicuous way to pave the way to full reproducibility of our results. ::: ::: Availability: GeNo, including its underlying resources, will be available from www.julielab.de. It is also currently deployed in the Semedico search engine at www.semedico.org. ::: ::: Contact: joachim.wermter@uni-jena.de
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paper_title: Disambiguating proteins, genes, and RNA in text: a machine learning approach

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We present an automated system for assigning protein, gene, or mRNA class labels to biological terms in free text. Three machine learning algorithms and several extended ways for defining contextual features for disambiguation are examined, and a fully unsupervised manner for obtaining training examples is proposed. We train and evaluate our system over a collection of 9 million words of molecular biology journal articles, obtaining accuracy rates up to 85%.
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paper_title: Overview of the BioCreative III Workshop

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The overall goal of the BioCreative Workshops is to promote the development of text mining and text processing tools which are useful to the communities of researchers and database curators in the biological sciences. To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature. Participants in the workshops were invited to compete in the tasks by constructing software systems to perform the tasks automatically and were given scores based on their performance. The results of these workshops have benefited the community in several ways. They have 1) provided evidence for the most effective methods currently available to solve specific problems; 2) revealed the current state of the art for performance on those problems; 3) and provided gold standard data and results on that data by which future advances can be gauged. This special issue contains overview papers for the three tasks of BioCreative III. The BioCreative III Workshop was held in September of 2010 and continued the tradition of a challenge evaluation on several tasks judged basic to effective text mining in biology, including a gene normalization (GN) task and two protein-protein interaction (PPI) tasks. In total the Workshop involved the work of twenty-three teams. Thirteen teams participated in the GN task which required the assignment of EntrezGene IDs to all named genes in full text papers without any species information being provided to a system. Ten teams participated in the PPI article classification task (ACT) requiring a system to classify and rank a PubMed® record as belonging to an article either having or not having “PPI relevant” information. Eight teams participated in the PPI interaction method task (IMT) where systems were given full text documents and were required to extract the experimental methods used to establish PPIs and a text segment supporting each such method. Gold standard data was compiled for each of these tasks and participants competed in developing systems to perform the tasks automatically. BioCreative III also introduced a new interactive task (IAT), run as a demonstration task. The goal was to develop an interactive system to facilitate a user’s annotation of the unique database identifiers for all the genes appearing in an article. This task included ranking genes by importance (based preferably on the amount of described experimental information regarding genes). There was also an optional task to assist the user in finding the most relevant articles about a given gene. For BioCreative III, a user advisory group (UAG) was assembled and played an important role 1) in producing some of the gold standard annotations for the GN task, 2) in critiquing IAT systems, and 3) in providing guidance for a future more rigorous evaluation of IAT systems. Six teams participated in the IAT demonstration task and received feedback on their systems from the UAG group. Besides innovations in the GN and PPI tasks making them more realistic and practical and the introduction of the IAT task, discussions were begun on community data standards to promote interoperability and on user requirements and evaluation metrics to address utility and usability of systems. In this paper we give a brief history of the BioCreative Workshops and how they relate to other text mining competitions in biology. This is followed by a synopsis of the three tasks GN, PPI, and IAT in BioCreative III with figures for best participant performance on the GN and PPI tasks. These results are discussed and compared with results from previous BioCreative Workshops and we conclude that the best performing systems for GN, PPI-ACT and PPI-IMT in realistic settings are not sufficient for fully automatic use. This provides evidence for the importance of interactive systems and we present our vision of how best to construct an interactive system for a GN or PPI like task in the remainder of the paper.
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paper_title: EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

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A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web.
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paper_title: Overview of the Infectious Diseases (ID) task of BioNLP Shared Task 2011

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This paper presents the preparation, resources, results and analysis of the Infectious Diseases (ID) information extraction task, a main task of the BioNLP Shared Task 2011. The ID task represents an application and extension of the BioNLP'09 shared task event extraction approach to full papers on infectious diseases. Seven teams submitted final results to the task, with the highest-performing system achieving 56% F-score in the full task, comparable to state-of-the-art performance in the established BioNLP'09 task. The results indicate that event extraction methods generalize well to new domains and full-text publications and are applicable to the extraction of events relevant to the molecular mechanisms of infectious diseases.
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paper_title: Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

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BackgroundGenomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease.ResultsThe filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing.In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease in several important databases on genetic disorders.ConclusionInformation based on the proximity postprocessing method we suggest is of sufficient quality to be profitably used for subsequent applications aimed at uncovering new biomedical knowledge. Although proximity filtering is only marginally effective for enhancing the precision of relations extracted with co-occurrence processing, it is likely to benefit methods based, even partially, on syntactic structure, regardless of the relation.
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paper_title: Algorithms and semantic infrastructure for mutation impact extraction and grounding

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BackgroundMutation impact extraction is a hitherto unaccomplished task in state of the art mutation extraction systems. Protein mutations and their impacts on protein properties are hidden in scientific literature, making them poorly accessible for protein engineers and inaccessible for phenotype-prediction systems that currently depend on manually curated genomic variation databases.ResultsWe present the first rule-based approach for the extraction of mutation impacts on protein properties, categorizing their directionality as positive, negative or neutral. Furthermore protein and mutation mentions are grounded to their respective UniProtKB IDs and selected protein properties, namely protein functions to concepts found in the Gene Ontology. The extracted entities are populated to an OWL-DL Mutation Impact ontology facilitating complex querying for mutation impacts using SPARQL. We illustrate retrieval of proteins and mutant sequences for a given direction of impact on specific protein properties. Moreover we provide programmatic access to the data through semantic web services using the SADI (Semantic Automated Discovery and Integration) framework.ConclusionWe address the problem of access to legacy mutation data in unstructured form through the creation of novel mutation impact extraction methods which are evaluated on a corpus of full-text articles on haloalkane dehalogenases, tagged by domain experts. Our approaches show state of the art levels of precision and recall for Mutation Grounding and respectable level of precision but lower recall for the task of Mutant-Impact relation extraction. The system is deployed using text mining and semantic web technologies with the goal of publishing to a broad spectrum of consumers.
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paper_title: Overview of BioNLP’09 Shared Task on Event Extraction

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The paper presents the design and implementation of the BioNLP'09 Shared Task, and reports the final results with analysis. The shared task consists of three sub-tasks, each of which addresses bio-molecular event extraction at a different level of specificity. The data was developed based on the GENIA event corpus. The shared task was run over 12 weeks, drawing initial interest from 42 teams. Of these teams, 24 submitted final results. The evaluation results are encouraging, indicating that state-of-the-art performance is approaching a practically applicable level and revealing some remaining challenges.
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paper_title: Extracting Complex Biological Events with Rich Graph-Based Feature Sets

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We describe a system for extracting complex events among genes and proteins from biomedical literature, developed in context of the BioNLP'09 Shared Task on Event Extraction. For each event, its text trigger, class, and arguments are extracted. In contrast to the prevailing approaches in the domain, events can be arguments of other events, resulting in a nested structure that better captures the underlying biological statements. We divide the task into independent steps which we approach as machine learning problems. We define a wide array of features and in particular make extensive use of dependency parse graphs. A rule-based post-processing step is used to refine the output in accordance with the restrictions of the extraction task. In the shared task evaluation, the system achieved an F-score of 51.95% on the primary task, the best performance among the participants.
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paper_title: Model Combination for Event Extraction in BioNLP 2011

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We describe the FAUST entry to the BioNLP 2011 shared task on biomolecular event extraction. The FAUST system explores several stacking models for combination using as base models the UMass dual decomposition (Riedel and McCallum, 2011) and Stanford event parsing (McClosky et al., 2011b) approaches. We show that using stacking is a straightforward way to improving performance for event extraction and find that it is most effective when using a small set of stacking features and the base models use slightly different representations of the input data. The FAUST system obtained 1st place in three out of four tasks: 1st place in Genia Task 1 (56.0% f-score) and Task 2 (53.9%), 2nd place in the Epigenetics and Post-translational Modifications track (35.0%), and 1st place in the Infectious Diseases track (55.6%).
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paper_title: MutationFinder: a high-performance system for extracting point mutation mentions from text

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Summary ::: Discussion of point mutations is ubiquitous in biomedical literature, and manually compiling databases or literature on mutations in specific genes or proteins is tedious. We present an open-source, rule-based system, MutationFinder, for extracting point mutation mentions from text. On blind test data, it achieves nearly perfect precision and a markedly improved recall over a baseline.
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paper_title: OSIRISv1.2: A named entity recognition system for sequence variants of genes in biomedical literature

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BackgroundSingle Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required.ResultsOur group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes http://ibi.imim.es/osirisform.html. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, http://ibi.imim.es/OSIRISv1.2.html) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented.ConclusionOSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.
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paper_title: Overview of BioCreAtIvE: critical assessment of information extraction for biology

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BackgroundThe goal of the first BioCreAtIvE challenge (Critical Assessment of Information Extraction in Biology) was to provide a set of common evaluation tasks to assess the state of the art for text mining applied to biological problems. The results were presented in a workshop held in Granada, Spain March 28–31, 2004. The articles collected in this BMC Bioinformatics supplement entitled "A critical assessment of text mining methods in molecular biology" describe the BioCreAtIvE tasks, systems, results and their independent evaluation.ResultsBioCreAtIvE focused on two tasks. The first dealt with extraction of gene or protein names from text, and their mapping into standardized gene identifiers for three model organism databases (fly, mouse, yeast). The second task addressed issues of functional annotation, requiring systems to identify specific text passages that supported Gene Ontology annotations for specific proteins, given full text articles.ConclusionThe first BioCreAtIvE assessment achieved a high level of international participation (27 groups from 10 countries). The assessment provided state-of-the-art performance results for a basic task (gene name finding and normalization), where the best systems achieved a balanced 80% precision / recall or better, which potentially makes them suitable for real applications in biology. The results for the advanced task (functional annotation from free text) were significantly lower, demonstrating the current limitations of text-mining approaches where knowledge extrapolation and interpretation are required. In addition, an important contribution of BioCreAtIvE has been the creation and release of training and test data sets for both tasks. There are 22 articles in this special issue, including six that provide analyses of results or data quality for the data sets, including a novel inter-annotator consistency assessment for the test set used in task 2.
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paper_title: Gene mention normalization and interaction extraction with context models and sentence motifs

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Background:The goal of text mining is to make the information conveyed in scientific publications accessible to structured search and automatic analysis. Two important subtasks of text mining are entity mention normalization - to identify biomedical objects in text - and extraction of qualified relationships between those objects. We describe a method for identifying genes and relationships between proteins.Results:We present solutions to gene mention normalization and extraction of protein-protein interactions. For the first task, we identify genes by using background knowledge on each gene, namely annotations related to function, location, disease, and so on. Our approach currently achieves an f-measure of 86.4% on the BioCreative II gene normalization data. For the extraction of protein-protein interactions, we pursue an approach that builds on classical sequence analysis: motifs derived from multiple sequence alignments. The method achieves an f-measure of 24.4% (micro-average) in the BioCreative II interaction pair subtask.Conclusion:For gene mention normalization, our approach outperforms strategies that utilize only the matching of genes names against dictionaries, without invoking further knowledge on each gene. Motifs derived from alignments of sentences are successful at identifying protein interactions in text; the approach we present in this report is fully automated and performs similarly to systems that require human intervention at one or more stages.Availability:Our methods for gene, protein, and species identification, and extraction of protein-protein are available as part of the BioCreative Meta Services (BCMS), see http://bcms.bioinfo.cnio.es/.
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paper_title: GenDrux: A biomedical literature search system to identify gene expression-based drug sensitivity in breast cancer

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Background ::: This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications.
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paper_title: Mayo clinical Text Analysis and Knowledge Extraction System (cTAKES): architecture, component evaluation and applications

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We aim to build and evaluate an open-source natural language processing system for information extraction from electronic medical record clinical free-text. We describe and evaluate our system, the clinical Text Analysis and Knowledge Extraction System (cTAKES), released open-source at . The cTAKES builds on existing open-source technologies—the Unstructured Information Management Architecture framework and OpenNLP natural language processing toolkit. Its components, specifically trained for the clinical domain, create rich linguistic and semantic annotations. Performance of individual components: sentence boundary detector accuracy=0.949; tokenizer accuracy=0.949; part-of-speech tagger accuracy=0.936; shallow parser F-score=0.924; named entity recognizer and system-level evaluation F-score=0.715 for exact and 0.824 for overlapping spans, and accuracy for concept mapping, negation, and status attributes for exact and overlapping spans of 0.957, 0.943, 0.859, and 0.580, 0.939, and 0.839, respectively. Overall performance is discussed against five applications. The cTAKES annotations are the foundation for methods and modules for higher-level semantic processing of clinical free-text.
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paper_title: System Evaluation on a Named Entity Corpus from Clinical Notes

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This paper presents the evaluation of the dictionary look-up component of Mayo Clinic’s Information Extraction system. The component was tested on a corpus of 160 free-text clinical notes which were manually annotated with the named entity disease. This kind of clinical text presents many language challenges such as fragmented sentences and heavy use of abbreviations and acronyms. The dictionary used for this evaluation was a subset of SNOMED-CT with semantic types corresponding to diseases/disorders without any augmentation. The algorithm achieves an F-score of 0.56 for exact matches and F-scores of 0.76 and 0.62 for right and left-partial matches respectively. Machine learning techniques are currently under investigation to improve this task.
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paper_title: Conditional Random Fields and Support Vector Machines for Disorder Named Entity Recognition in Clinical Texts

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We present a comparative study between two machine learning methods, Conditional Random Fields and Support Vector Machines for clinical named entity recognition. We explore their applicability to clinical domain. Evaluation against a set of gold standard named entities shows that CRFs outperform SVMs. The best F-score with CRFs is 0.86 and for the SVMs is 0.64 as compared to a baseline of 0.60.
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paper_title: Combining Terminology Resources and Statistical Methods for Entity Recognition: an Evaluation

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Terminologies and other knowledge resources are widely used to aid entity recognition in specialist domain texts. As well as providing lexicons of specialist terms, linkage from the text back to a resource can make additional knowledge available to applications. Use of such resources is especially pertinent in the biomedical domain, where large numbers of these resources are available, and where they are widely used in informatics applications. Terminology resources can be most readily used by simple lexical lookup of terms in the text. A major drawback with such lexical lookup, however, is poor precision caused by ambiguity between domain terms and general language words. We combine lexical lookup with simple filtering of ambiguous terms, to improve precision. We compare this lexical lookup with a statistical method of entity recognition, and to a method which combines the two approaches. We show that the combined method boosts precision with little loss of recall, and that linkage from recognised entities back to the domain knowledge resources can
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paper_title: Extracting information from textual documents in the electronic health record: a review of recent research.

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Objectives: We examine recent published research on the extraction of information from textual documents in the Electronic Health Record (EHR). Methods: Literature review of the research published after 1995, based on PubMed, conference proceedings, and the ACM Digital Library, as well as on relevant publications referenced in papers already included. Results: 174 publications were selected and are discussed in this review in terms of methods used, pre-processing of textual documents, contextual features detection and analysis, extraction of information in general, extraction of codes and of information for decision-support and enrichment of the EHR, information extraction for surveillance, research, automated terminology management, and data mining, and de-identification of clinical text. Conclusions: Performance of information extraction systems with clinical text has improved since the last systematic review in 1995, but they are still rarely applied outside of the laboratory they have been developed in. Competitive challenges for information extraction from clinical text, along with the availability of annotated clinical text corpora, and further improvements in system performance are important factors to stimulate advances in this field and to increase the acceptance and usage of these systems in concrete clinical and biomedical research contexts. Cli
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paper_title: Classifying Semantic Relations In Bioscience Texts

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A crucial step toward the goal of automatic extraction of propositional information from natural language text is the identification of semantic relations between constituents in sentences. We examine the problem of distinguishing among seven relation types that can occur between the entities "treatment" and "disease" in bioscience text, and the problem of identifying such entities. We compare five generative graphical models and a neural network, using lexical, syntactic, and semantic features, finding that the latter help achieve high classification accuracy.
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paper_title: BANNER: An Executable Survey of Advances in Biomedical Named Entity Recognition

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There has been an increasing amount of research on biomedical named entity recognition, t he most basic text extraction problem, resulting in significant progress by different research teams around the world. This has created a need for a freely-available, open source system implementing the advances described in the literature. In this paper we present BANNER, an open-source, executable survey of advances in biomedical named entity recognition, intended to serve as a benchmark for the field. BANNER is implemented in Java as a machine-learning system based on conditional random fields and includes a wide survey of the best techniques recently described in the literature. It is designed to maximize domain independence by not employing brittle semantic features or rule-based processing steps, and achieves significantly better performance than existing baseline systems. It is therefore useful to developers as an extensible NER implementation, to researchers as a standard for comparing innovative techniques, and to biologists requiring the ability to find novel entities in large amounts of text. BANNER is available for download at http://banner.sourceforge.net.
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paper_title: Automatic de-identification of textual documents in the electronic health record: a review of recent research

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BackgroundIn the United States, the Health Insurance Portability and Accountability Act (HIPAA) protects the confidentiality of patient data and requires the informed consent of the patient and approval of the Internal Review Board to use data for research purposes, but these requirements can be waived if data is de-identified. For clinical data to be considered de-identified, the HIPAA "Safe Harbor" technique requires 18 data elements (called PHI: Protected Health Information) to be removed. The de-identification of narrative text documents is often realized manually, and requires significant resources. Well aware of these issues, several authors have investigated automated de-identification of narrative text documents from the electronic health record, and a review of recent research in this domain is presented here.MethodsThis review focuses on recently published research (after 1995), and includes relevant publications from bibliographic queries in PubMed, conference proceedings, the ACM Digital Library, and interesting publications referenced in already included papers.ResultsThe literature search returned more than 200 publications. The majority focused only on structured data de-identification instead of narrative text, on image de-identification, or described manual de-identification, and were therefore excluded. Finally, 18 publications describing automated text de-identification were selected for detailed analysis of the architecture and methods used, the types of PHI detected and removed, the external resources used, and the types of clinical documents targeted. All text de-identification systems aimed to identify and remove person names, and many included other types of PHI. Most systems used only one or two specific clinical document types, and were mostly based on two different groups of methodologies: pattern matching and machine learning. Many systems combined both approaches for different types of PHI, but the majority relied only on pattern matching, rules, and dictionaries.ConclusionsIn general, methods based on dictionaries performed better with PHI that is rarely mentioned in clinical text, but are more difficult to generalize. Methods based on machine learning tend to perform better, especially with PHI that is not mentioned in the dictionaries used. Finally, the issues of anonymization, sufficient performance, and "over-scrubbing" are discussed in this publication.
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paper_title: Assessment of commercial NLP engines for medication information extraction from dictated clinical notes.

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Abstract Purpose We assessed the current state of commercial natural language processing (NLP) engines for their ability to extract medication information from textual clinical documents. Methods Two thousand de-identified discharge summaries and family practice notes were submitted to four commercial NLP engines with the request to extract all medication information. The four sets of returned results were combined to create a comparison standard which was validated against a manual, physician-derived gold standard created from a subset of 100 reports. Once validated, the individual vendor results for medication names, strengths, route, and frequency were compared against this automated standard with precision, recall, and F measures calculated. Results Compared with the manual, physician-derived gold standard, the automated standard was successful at accurately capturing medication names ( F measure=93.2%), but performed less well with strength (85.3%) and route (80.3%), and relatively poorly with dosing frequency (48.3%). Moderate variability was seen in the strengths of the four vendors. The vendors performed better with the structured discharge summaries than with the clinic notes in an analysis comparing the two document types. Conclusion Although automated extraction may serve as the foundation for a manual review process, it is not ready to automate medication lists without human intervention.
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paper_title: Integration of text- and data-mining using ontologies successfully selects disease gene candidates

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Genome-wide techniques such as microarray analysis, Serial Analysis of Gene Expression (SAGE), Massively Parallel Signature Sequencing (MPSS), linkage analysis and association studies are used extensively in the search for genes that cause diseases, and often identify many hundreds of candidate disease genes. Selection of the most probable of these candidate disease genes for further empirical analysis is a significant challenge. Additionally, identifying the genes that cause complex diseases is problematic due to low penetrance of multiple contributing genes. Here, we describe a novel bioinformatic approach that selects candidate disease genes according to their expression profiles. We use the eVOC anatomical ontology to integrate text-mining of biomedical literature and data-mining of available human gene expression data. To demonstrate that our method is successful and widely applicable, we apply it to a database of 417 candidate genes containing 17 known disease genes. We successfully select the known disease gene for 15 out of 17 diseases and reduce the candidate gene set to 63.3% (618.8%) of its original size. This approach facilitates direct association between genomic data describing gene expression and information from biomedical texts describing disease phenotype, and successfully prioritizes candidate genes according to their expression in disease-affected tissues.
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paper_title: A dictionary to identify small molecules and drugs in free text

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Motivation: From the scientific community, a lot of effort has been spent on the correct identification of gene and protein names in text, while less effort has been spent on the correct identification of chemical names. Dictionary-based term identification has the power to recognize the diverse representation of chemical information in the literature and map the chemicals to their database identifiers. ::: ::: Results: We developed a dictionary for the identification of small molecules and drugs in text, combining information from UMLS, MeSH, ChEBI, DrugBank, KEGG, HMDB and ChemIDplus. Rule-based term filtering, manual check of highly frequent terms and disambiguation rules were applied. We tested the combined dictionary and the dictionaries derived from the individual resources on an annotated corpus, and conclude the following: (i) each of the different processing steps increase precision with a minor loss of recall; (ii) the overall performance of the combined dictionary is acceptable (precision 0.67, recall 0.40 (0.80 for trivial names); (iii) the combined dictionary performed better than the dictionary in the chemical recognizer OSCAR3; (iv) the performance of a dictionary based on ChemIDplus alone is comparable to the performance of the combined dictionary. ::: ::: Availability: The combined dictionary is freely available as an XML file in Simple Knowledge Organization System format on the web site http://www.biosemantics.org/chemlist. ::: ::: Contact: k.hettne@erasmusmc.nl ::: ::: Supplementary information:Supplementary data are available at Bioinformatics online.
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paper_title: Integrating existing natural language processing tools for medication extraction from discharge summaries

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Objective: To develop an automated system to extract medications and related information from discharge summaries as part of the 2009 i2b2 natural language processing (NLP) challenge. This task required accurate recognition of medication name, dosage, mode, frequency, duration, and reason for drug administration. ::: ::: Design: We developed an integrated system using several existing NLP components developed at Vanderbilt University Medical Center, which included MedEx (to extract medication information), SecTag (a section identification system for clinical notes), a sentence splitter, and a spell checker for drug names. Our goal was to achieve good performance with minimal to no specific training for this document corpus; thus, evaluating the portability of those NLP tools beyond their home institution. The integrated system was developed using 17 notes that were annotated by the organizers and evaluated using 251 notes that were annotated by participating teams. ::: ::: Measurements: The i2b2 challenge used standard measures, including precision, recall, and F-measure, to evaluate the performance of participating systems. There were two ways to determine whether an extracted textual finding is correct or not: exact matching or inexact matching. The overall performance for all six types of medication-related findings across 251 annotated notes was considered as the primary metric in the challenge. ::: ::: Results: Our system achieved an overall F-measure of 0.821 for exact matching (0.839 precision; 0.803 recall) and 0.822 for inexact matching (0.866 precision; 0.782 recall). The system ranked second out of 20 participating teams on overall performance at extracting medications and related information. ::: ::: Conclusions: The results show that the existing MedEx system, together with other NLP components, can extract medication information in clinical text from institutions other than the site of algorithm development with reasonable performance.
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paper_title: Relation extraction for drug-drug interactions using ensemble learning

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We describe our approach for the extraction of drug-drug in- teractions from literature. The proposed method builds majority voting ensembles of contrasting machine learning methods, which exploit dier- ent linguistic feature spaces. We evaluated our approach in the context of the DDI Extraction 2011 challenge, where using document-wise cross- validation, the best single classier achieved an F 1 of 57.3 % and the best ensemble achieved 60.6 %. On the held out test set, our best run achieved a F1 of 65.7 %.
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paper_title: Discovery and Explanation of Drug-Drug Interactions via Text Mining

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Drug-drug interactions (DDIs) can occur when two drugs interact with the same gene product. Most available information about gene-drug relationships is contained within the scientific literature, but is dispersed over a large number of publications, with thousands of new publications added each month. In this setting, automated text mining is an attractive solution for identifying gene-drug relationships and aggregating them to predict novel DDIs. In previous work, we have shown that gene-drug interactions can be extracted from Medline abstracts with high fidelity - we extract not only the genes and drugs, but also the type of relationship expressed in individual sentences (e.g. metabolize, inhibit, activate and many others). We normalize these relationships and map them to a standardized ontology. In this work, we hypothesize that we can combine these normalized gene-drug relationships, drawn from a very broad and diverse literature, to infer DDIs. Using a training set of established DDIs, we have trained a random forest classifier to score potential DDIs based on the features of the normalized assertions extracted from the literature that relate two drugs to a gene product. The classifier recognizes the combinations of relationships, drugs and genes that are most associated with the gold standard DDIs, correctly identifying 79.8% of assertions relating interacting drug pairs and 78.9% of assertions relating noninteracting drug pairs. Most significantly, because our text processing method captures the semantics of individual gene-drug relationships, we can construct mechanistic pharmacological explanations for the newly-proposed DDIs. We show how our classifier can be used to explain known DDIs and to uncover new DDIs that have not yet been reported.
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paper_title: Extracting drug-drug interactions from biomedical texts

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Background A drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The detection of drug interactions is an important research area in patient safety since these interactions can become very dangerous and increase health care costs. Although there are different databases supporting health care professionals in the detection of drug interactions, this kind of resources is rarely complete. Drug interactions are frequently reported in journals of clinical pharmacology, making medical literature the most effective source for the detection of drug interactions. However, the increasing volume of the literature overwhelms health care professionals trying to keep an up-to-date collection of all reported DDIs. The development of automatic methods for collecting, maintaining and
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paper_title: OSCAR4: a flexible architecture for chemical text-mining

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The Open-Source Chemistry Analysis Routines (OSCAR) software, a toolkit for the recognition of named entities and data in chemistry publications, has been developed since 2002. Recent work has resulted in the separation of the core OSCAR functionality and its release as the OSCAR4 library. This library features a modular API (based on reduction of surface coupling) that permits client programmers to easily incorporate it into external applications. OSCAR4 offers a domain-independent architecture upon which chemistry specific text-mining tools can be built, and its development and usage are discussed.
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paper_title: Extracting medication information from clinical text

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The Third i2b2 Workshop on Natural Language Processing Challenges for Clinical Records focused on the identification of medications, their dosages, modes (routes) of administration, frequencies, durations, and reasons for administration in discharge summaries. This challenge is referred to as the medication challenge. For the medication challenge, i2b2 released detailed annotation guidelines along with a set of annotated discharge summaries. Twenty teams representing 23 organizations and nine countries participated in the medication challenge. The teams produced rule-based, machine learning, and hybrid systems targeted to the task. Although rule-based systems dominated the top 10, the best performing system was a hybrid. Of all medication-related fields, durations and reasons were the most difficult for all systems to detect. While medications themselves were identified with better than 0.75 F-measure by all of the top 10 systems, the best F-measure for durations and reasons were 0.525 and 0.459, respectively. State-of-the-art natural language processing systems go a long way toward extracting medication names, dosages, modes, and frequencies. However, they are limited in recognizing duration and reason fields and would benefit from future research.
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paper_title: A cascade of classifiers for extracting medication information from discharge summaries

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BackgroundExtracting medication information from clinical records has many potential applications, and recently published research, systems, and competitions reflect an interest therein. Much of the early extraction work involved rules and lexicons, but more recently machine learning has been applied to the task.MethodsWe present a hybrid system consisting of two parts. The first part, field detection, uses a cascade of statistical classifiers to identify medication-related named entities. The second part uses simple heuristics to link those entities into medication events.ResultsThe system achieved performance that is comparable to other approaches to the same task. This performance is further improved by adding features that reference external medication name lists.ConclusionsThis study demonstrates that our hybrid approach outperforms purely statistical or rule-based systems. The study also shows that a cascade of classifiers works better than a single classifier in extracting medication information. The system is available as is upon request from the first author.
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paper_title: MedEx: a medication information extraction system for clinical narratives.

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Medication information is one of the most important types of clinical data in electronic medical records. It is critical for healthcare safety and quality, as well as for clinical research that uses electronic medical record data. However, medication data are often recorded in clinical notes as free-text. As such, they are not accessible to other computerized applications that rely on coded data. We describe a new natural language processing system (MedEx), which extracts medication information from clinical notes. MedEx was initially developed using discharge summaries. An evaluation using a data set of 50 discharge summaries showed it performed well on identifying not only drug names (F-measure 93.2%), but also signature information, such as strength, route, and frequency, with F-measures of 94.5%, 93.9%, and 96.0% respectively. We then applied MedEx unchanged to outpatient clinic visit notes. It performed similarly with F-measures over 90% on a set of 25 clinic visit notes.
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paper_title: ChemicalTagger: A tool for semantic text-mining in chemistry

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The primary method for scientific communication is in the form of published scientific articles and theses which use natural language combined with domain-specific terminology. As such, they contain free owing unstructured text. Given the usefulness of data extraction from unstructured literature, we aim to show how this can be achieved for the discipline of chemistry. The highly formulaic style of writing most chemists adopt make their contributions well suited to high-throughput Natural Language Processing (NLP) approaches. We have developed the ChemicalTagger parser as a medium-depth, phrase-based semantic NLP tool for the language of chemical experiments. Tagging is based on a modular architecture and uses a combination of OSCAR, domain-specific regex and English taggers to identify parts-of-speech. The ANTLR grammar is used to structure this into tree-based phrases. Using a metric that allows for overlapping annotations, we achieved machine-annotator agreements of 88.9% for phrase recognition and 91.9% for phrase-type identification (Action names). It is possible parse to chemical experimental text using rule-based techniques in conjunction with a formal grammar parser. ChemicalTagger has been deployed for over 10,000 patents and has identified solvents from their linguistic context with >99.5% precision.
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paper_title: The structural and content aspects of abstracts versus bodies of full text journal articles are different

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BackgroundAn increase in work on the full text of journal articles and the growth of PubMedCentral have the opportunity to create a major paradigm shift in how biomedical text mining is done. However, until now there has been no comprehensive characterization of how the bodies of full text journal articles differ from the abstracts that until now have been the subject of most biomedical text mining research.ResultsWe examined the structural and linguistic aspects of abstracts and bodies of full text articles, the performance of text mining tools on both, and the distribution of a variety of semantic classes of named entities between them. We found marked structural differences, with longer sentences in the article bodies and much heavier use of parenthesized material in the bodies than in the abstracts. We found content differences with respect to linguistic features. Three out of four of the linguistic features that we examined were statistically significantly differently distributed between the two genres. We also found content differences with respect to the distribution of semantic features. There were significantly different densities per thousand words for three out of four semantic classes, and clear differences in the extent to which they appeared in the two genres. With respect to the performance of text mining tools, we found that a mutation finder performed equally well in both genres, but that a wide variety of gene mention systems performed much worse on article bodies than they did on abstracts. POS tagging was also more accurate in abstracts than in article bodies.ConclusionsAspects of structure and content differ markedly between article abstracts and article bodies. A number of these differences may pose problems as the text mining field moves more into the area of processing full-text articles. However, these differences also present a number of opportunities for the extraction of data types, particularly that found in parenthesized text, that is present in article bodies but not in article abstracts.
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paper_title: Overview of BioNLP’09 Shared Task on Event Extraction

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The paper presents the design and implementation of the BioNLP'09 Shared Task, and reports the final results with analysis. The shared task consists of three sub-tasks, each of which addresses bio-molecular event extraction at a different level of specificity. The data was developed based on the GENIA event corpus. The shared task was run over 12 weeks, drawing initial interest from 42 teams. Of these teams, 24 submitted final results. The evaluation results are encouraging, indicating that state-of-the-art performance is approaching a practically applicable level and revealing some remaining challenges.
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paper_title: Drug name recognition and classification in biomedical texts. A case study outlining approaches underpinning automated systems.

paper_content:

This article presents a system for drug name recognition and classification in biomedical texts. The system combines information obtained by the Unified Medical Language System (UMLS) MetaMap Transfer (MMTx) program and nomenclature rules recommended by the World Health Organization (WHO) International Nonproprietary Names (INNs) Program to identify and classify pharmaceutical substances. Moreover, the system is able to detect possible candidates for drug names that have not been detected by MMTx program by applying these rules, achieving, in this way, a broader coverage. This work is the first step in a method for automatic detection of drug interactions from biomedical texts, a specific type of adverse drug event of special interest in patient safety.
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paper_title: The 1st DDIExtraction-2011 challenge task: Extraction of Drug-Drug Interactions from biomedical texts Challenge Task on Drug-Drug Interaction Extraction

paper_content:

We present an evaluation task designed to provide a frame- work for comparing different approaches to extracting drug-drug interac- tions from biomedical texts. We define the task, describe the training/test data, list the participating systems and discuss their results. There were 10 teams who submitted a total of 40 runs.
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paper_title: A linguistic rule-based approach to extract drug-drug interactions from pharmacological documents

paper_content:

BackgroundA drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The increasing volume of the scientific literature overwhelms health care professionals trying to be kept up-to-date with all published studies on DDI.MethodsThis paper describes a hybrid linguistic approach to DDI extraction that combines shallow parsing and syntactic simplification with pattern matching. Appositions and coordinate structures are interpreted based on shallow syntactic parsing provided by the UMLS MetaMap tool (MMTx). Subsequently, complex and compound sentences are broken down into clauses from which simple sentences are generated by a set of simplification rules. A pharmacist defined a set of domain-specific lexical patterns to capture the most common expressions of DDI in texts. These lexical patterns are matched with the generated sentences in order to extract DDIs.ResultsWe have performed different experiments to analyze the performance of the different processes. The lexical patterns achieve a reasonable precision (67.30%), but very low recall (14.07%). The inclusion of appositions and coordinate structures helps to improve the recall (25.70%), however, precision is lower (48.69%). The detection of clauses does not improve the performance.ConclusionsInformation Extraction (IE) techniques can provide an interesting way of reducing the time spent by health care professionals on reviewing the literature. Nevertheless, no approach has been carried out to extract DDI from texts. To the best of our knowledge, this work proposes the first integral solution for the automatic extraction of DDI from biomedical texts.
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paper_title: Cascaded classifiers for confidence-based chemical named entity recognition

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BackgroundChemical named entities represent an important facet of biomedical text.ResultsWe have developed a system to use character-based n-grams, Maximum Entropy Markov Models and rescoring to recognise chemical names and other such entities, and to make confidence estimates for the extracted entities. An adjustable threshold allows the system to be tuned to high precision or high recall. At a threshold set for balanced precision and recall, we were able to extract named entities at an F score of 80.7% from chemistry papers and 83.2% from PubMed abstracts. Furthermore, we were able to achieve 57.6% and 60.3% recall at 95% precision, and 58.9% and 49.1% precision at 90% recall.ConclusionThese results show that chemical named entities can be extracted with good performance, and that the properties of the extraction can be tuned to suit the demands of the task.
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paper_title: Discovering drug–drug interactions: a text-mining and reasoning approach based on properties of drug metabolism

paper_content:

Motivation: Identifying drug–drug interactions (DDIs) is a critical process in drug administration and drug development. Clinical support tools often provide comprehensive lists of DDIs, but they usually lack the supporting scientific evidences and different tools can return inconsistent results. In this article, we propose a novel approach that integrates text mining and automated reasoning to derive DDIs. Through the extraction of various facts of drug metabolism, not only the DDIs that are explicitly mentioned in text can be extracted but also the potential interactions that can be inferred by reasoning. ::: ::: Results: Our approach was able to find several potential DDIs that are not present in DrugBank. We manually evaluated these interactions based on their supporting evidences, and our analysis revealed that 81.3% of these interactions are determined to be correct. This suggests that our approach can uncover potential DDIs with scientific evidences explaining the mechanism of the interactions. ::: ::: Contact: luis.tari@roche.com
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paper_title: Extraction and Mapping of Drug Names from Free Text to a Standardized Nomenclature

paper_content:

Free text fields are often used to store clinical drug data in electronic health records. The use of free text facilitates rapid data entry by the clinician. Errors in spelling, abbreviations, and jargon, however, limit the utility of these data. We designed and implemented an algorithm, using open source tools and RxNorm, to extract and normalize drug data stored in free text fields of an anesthesia electronic health record. The algorithm was developed using a training set containing drug data from 49,518 cases, and validated using a validation set containing data from 14,655 cases. Overall sensitivity and specificity for the validation set were 92.2% and 95.7% respectively. The mains sources of error were misspellings and unknown but valid drug names. These preliminary results demonstrate that free text clinical drug data can be efficiently extracted and mapped to a controlled drug nomenclature.
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paper_title: High accuracy information extraction of medication information from clinical notes: 2009 i2b2 medication extraction challenge

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Objective Medication information comprises a most valuable source of data in clinical records. This paper describes use of a cascade of machine learners that automatically extract medication information from clinical records. Design Authors developed a novel supervised learning model that incorporates two machine learning algorithms and several rule-based engines. Measurements Evaluation of each step included precision, recall and F-measure metrics. The final outputs of the system were scored using the i2b2 workshop evaluation metrics, including strict and relaxed matching with a gold standard. Results Evaluation results showed greater than 90% accuracy on five out of seven entities in the name entity recognition task, and an F-measure greater than 95% on the relationship classification task. The strict micro averaged F-measure for the system output achieved best submitted performance of the competition, at 85.65%. Limitations Clinical staff will only use practical processing systems if they have confidence in their reliability. Authors estimate that an acceptable accuracy for a such a working system should be approximately 95%. This leaves a significant performance gap of 5 to 10% from the current processing capabilities. Conclusion A multistage method with mixed computational strategies using a combination of rulebased classifiers and statistical classifiers seems to provide a near-optimal strategy for automated extraction of medication information from clinical records.
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paper_title: Integration of text- and data-mining using ontologies successfully selects disease gene candidates

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Genome-wide techniques such as microarray analysis, Serial Analysis of Gene Expression (SAGE), Massively Parallel Signature Sequencing (MPSS), linkage analysis and association studies are used extensively in the search for genes that cause diseases, and often identify many hundreds of candidate disease genes. Selection of the most probable of these candidate disease genes for further empirical analysis is a significant challenge. Additionally, identifying the genes that cause complex diseases is problematic due to low penetrance of multiple contributing genes. Here, we describe a novel bioinformatic approach that selects candidate disease genes according to their expression profiles. We use the eVOC anatomical ontology to integrate text-mining of biomedical literature and data-mining of available human gene expression data. To demonstrate that our method is successful and widely applicable, we apply it to a database of 417 candidate genes containing 17 known disease genes. We successfully select the known disease gene for 15 out of 17 diseases and reduce the candidate gene set to 63.3% (618.8%) of its original size. This approach facilitates direct association between genomic data describing gene expression and information from biomedical texts describing disease phenotype, and successfully prioritizes candidate genes according to their expression in disease-affected tissues.
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paper_title: Mayo clinical Text Analysis and Knowledge Extraction System (cTAKES): architecture, component evaluation and applications

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We aim to build and evaluate an open-source natural language processing system for information extraction from electronic medical record clinical free-text. We describe and evaluate our system, the clinical Text Analysis and Knowledge Extraction System (cTAKES), released open-source at . The cTAKES builds on existing open-source technologies—the Unstructured Information Management Architecture framework and OpenNLP natural language processing toolkit. Its components, specifically trained for the clinical domain, create rich linguistic and semantic annotations. Performance of individual components: sentence boundary detector accuracy=0.949; tokenizer accuracy=0.949; part-of-speech tagger accuracy=0.936; shallow parser F-score=0.924; named entity recognizer and system-level evaluation F-score=0.715 for exact and 0.824 for overlapping spans, and accuracy for concept mapping, negation, and status attributes for exact and overlapping spans of 0.957, 0.943, 0.859, and 0.580, 0.939, and 0.839, respectively. Overall performance is discussed against five applications. The cTAKES annotations are the foundation for methods and modules for higher-level semantic processing of clinical free-text.
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paper_title: Mining gene-disease relationships from biomedical literature: weighting protein-protein interactions and connectivity measures.

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Motivation: The promises of the post-genome era disease-related discoveries and advances have yet to be fully realized, with many opportunities for discovery hiding in the millions of biomedical papers published since. Public databases give access to data extracted from the literature by teams of experts, but their coverage is often limited and lags behind recent discoveries. We present a computational method that combines data extracted from the literature with data from curated sources in order to uncover possible gene-disease relationships that are not directly stated or were missed by the initial mining. Method: An initial set of genes and proteins is obtained from gene-disease relationships extracted from PubMed abstracts using natural language processing. Interactions involving the corresponding proteins are similarly extracted and integrated with interactions from curated databases (such as BIND and DIP), assigning a confidence measure to each interaction depending on its source. The augmented list of genes and gene products is then ranked combining two scores: one that reflects the strength of the relationship with the initial set of genes and incorporates user-defined weights and another that reflects the importance of the gene in maintaining the connectivity of the network. We applied the method to atherosclerosis to assess its effectiveness. Results: Top-ranked proteins from the method are related to atherosclerosis with accuracy between 0.85 to 1.00 for the top 20 and 0.64 to 0.80 for the top 90 if duplicates are ignored, with 45% of the top 20 and 75% of the top 90 derived by the method, not extracted from text. Thus, though the initial gene set and interactions were automatically extracted from text (and subject to the impreciseness of automatic extraction), their use for further hypothesis generation is valuable given adequate computational analysis.
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paper_title: INTEX: A Syntactic Role Driven Protein-Protein Interaction Extractor For Bio-Medical Text

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In this paper, we present a fully automated extraction system, named IntEx, to identify gene and protein interactions in biomedical text. Our approach is based on first splitting complex sentences into simple clausal structures made up of syntactic roles. Then, tagging biological entities with the help of biomedical and linguistic ontologies. Finally, extracting complete interactions by analyzing the matching contents of syntactic roles and their linguistically significant combinations. Our extraction system handles complex sentences and extracts multiple and nested interactions specified in a sentence. Experimental evaluations with two other state of the art extraction systems indicate that the IntEx system achieves better performance without the labor intensive pattern engineering requirement.
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paper_title: Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

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BackgroundGenomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease.ResultsThe filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing.In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease in several important databases on genetic disorders.ConclusionInformation based on the proximity postprocessing method we suggest is of sufficient quality to be profitably used for subsequent applications aimed at uncovering new biomedical knowledge. Although proximity filtering is only marginally effective for enhancing the precision of relations extracted with co-occurrence processing, it is likely to benefit methods based, even partially, on syntactic structure, regardless of the relation.
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paper_title: Semantic Relations Asserting the Etiology of Genetic Diseases

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Considerable research is being directed at extracting molecular biology information from text. Particularly challenging in this regard is to identify relations between entities, such as protein-protein interactions or molecular pathways. In this paper we present a natural language processing method for extracting causal relations between genetic phenomena and diseases. After presenting the results of a preliminary evaluation, we suggest the use of a graphical display application for viewing the semantic predications produced by the system.
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paper_title: Mining Alzheimer Disease Relevant Proteins from Integrated Protein Interactome Data

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Huge unrealized post-genome opportunities remain in the understanding of detailed molecular mechanisms for Alzheimer Disease (AD). In this work, we developed a computational method to rank-order AD-related proteins, based on an initial list of AD-related genes and public human protein interaction data. In this method, we first collected an initial seed list of 65 AD-related genes from the OMIM database and mapped them to 70 AD seed proteins. We then expanded the seed proteins to an enriched AD set of 765 proteins using protein interactions from the Online Predicated Human Interaction Database (OPHID). We showed that the expanded AD-related proteins form a highly connected and statistically significant protein interaction sub-network. We further analyzed the sub-network to develop an algorithm, which can be used to automatically score and rank-order each protein for its biological relevance to AD pathways(s). Our results show that functionally relevant AD proteins were consistently ranked at the top: among the top 20 of 765 expanded AD proteins, 19 proteins are confirmed to belong to the original 70 AD seed protein set. Our method represents a novel use of protein interaction network data for Alzheimer disease studies and may be generalized for other disease areas in the future.
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paper_title: Extraction of semantic biomedical relations from text using conditional random fields

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BackgroundThe increasing amount of published literature in biomedicine represents an immense source of knowledge, which can only efficiently be accessed by a new generation of automated information extraction tools. Named entity recognition of well-defined objects, such as genes or proteins, has achieved a sufficient level of maturity such that it can form the basis for the next step: the extraction of relations that exist between the recognized entities. Whereas most early work focused on the mere detection of relations, the classification of the type of relation is also of great importance and this is the focus of this work. In this paper we describe an approach that extracts both the existence of a relation and its type. Our work is based on Conditional Random Fields, which have been applied with much success to the task of named entity recognition.ResultsWe benchmark our approach on two different tasks. The first task is the identification of semantic relations between diseases and treatments. The available data set consists of manually annotated PubMed abstracts. The second task is the identification of relations between genes and diseases from a set of concise phrases, so-called GeneRIF (Gene Reference Into Function) phrases. In our experimental setting, we do not assume that the entities are given, as is often the case in previous relation extraction work. Rather the extraction of the entities is solved as a subproblem. Compared with other state-of-the-art approaches, we achieve very competitive results on both data sets. To demonstrate the scalability of our solution, we apply our approach to the complete human GeneRIF database. The resulting gene-disease network contains 34758 semantic associations between 4939 genes and 1745 diseases. The gene-disease network is publicly available as a machine-readable RDF graph.ConclusionWe extend the framework of Conditional Random Fields towards the annotation of semantic relations from text and apply it to the biomedical domain. Our approach is based on a rich set of textual features and achieves a performance that is competitive to leading approaches. The model is quite general and can be extended to handle arbitrary biological entities and relation types. The resulting gene-disease network shows that the GeneRIF database provides a rich knowledge source for text mining. Current work is focused on improving the accuracy of detection of entities as well as entity boundaries, which will also greatly improve the relation extraction performance.
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paper_title: Extraction of Gene-Disease Relations from Medline Using Domain Dictionaries and Machine Learning

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1.Tsujii Laboratory, Room 615, 7th Building of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan 2. CREST, Japan Science and Technology agency, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan 3. Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, AIST Waterfront Bio-IT Research Building, Aomi 2-42, Koto-ku, Tokyo, 135-0064, Japan 4. Integrated Database Team, Japan Biological Information Research Center, Japan Biological Informatics Consortium, AIST Waterfront Bio-IT Research Building, Aomi 2-42, Koto-ku, Tokyo, 135-0064, Japan 5. School of Informatics, University of Manchester POBox 88, Sackville St, MANCHESTER M60 1QD, UK E-mail: {chun,tsuruoka,jdkim,tsujii}@is.s.u-tokyo.ac.jp, {rshiba,nnagata,t-hishiki}@jbirc.aist.go.jp
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paper_title: Ontology-guided data preparation for discovering genotype-phenotype relationships

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BackgroundComplexity and amount of post-genomic data constitute two major factors limiting the application of Knowledge Discovery in Databases (KDD) methods in life sciences. Bio-ontologies may nowadays play key roles in knowledge discovery in life science providing semantics to data and to extracted units, by taking advantage of the progress of Semantic Web technologies concerning the understanding and availability of tools for knowledge representation, extraction, and reasoning.ResultsThis paper presents a method that exploits bio-ontologies for guiding data selection within the preparation step of the KDD process. We propose three scenarios in which domain knowledge and ontology elements such as subsumption, properties, class descriptions, are taken into account for data selection, before the data mining step. Each of these scenarios is illustrated within a case-study relative to the search of genotype-phenotype relationships in a familial hypercholesterolemia dataset. The guiding of data selection based on domain knowledge is analysed and shows a direct influence on the volume and significance of the data mining results.ConclusionsThe method proposed in this paper is an efficient alternative to numerical methods for data selection based on domain knowledge. In turn, the results of this study may be reused in ontology modelling and data integration.
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paper_title: A text-mining analysis of the human phenome

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A number of large-scale efforts are underway to define the relationships between genes and proteins in various species. But, few attempts have been made to systematically classify all such relationships at the phenotype level. Also, it is unknown whether such a phenotype map would carry biologically meaningful information. We have used text mining to classify over 5000 human phenotypes contained in the Online Mendelian Inheritance in Man database. We find that similarity between phenotypes reflects biological modules of interacting functionally related genes. These similarities are positively correlated with a number of measures of gene function, including relatedness at the level of protein sequence, protein motifs, functional annotation, and direct protein-protein interaction. Phenotype grouping reflects the modular nature of human disease genetics. Thus, phenotype mapping may be used to predict candidate genes for diseases as well as functional relations between genes and proteins. Such predictions will further improve if a unified system of phenotype descriptors is developed. The phenotype similarity data are accessible through a web interface at http://www.cmbi.ru.nl/MimMiner/.
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paper_title: arterial disease genome-wide association study of peripheral of the electronic medical record to enable a Leveraging informatics for genetic studies : use

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Background: There is significant interest in leveraging the electronic medical record (EMR) to conduct genome-wide association studies (GWAS). ::: ::: Methods: A biorepository of DNA and plasma was created by recruiting patients referred for non-invasive lower extremity arterial evaluation or stress ECG. Peripheral arterial disease (PAD) was defined as a resting/post-exercise ankle-brachial index (ABI) less than or equal to 0.9, a history of lower extremity revascularization, or having poorly compressible leg arteries. Controls were patients without evidence of PAD. Demographic data and laboratory values were extracted from the EMR. Medication use and smoking status were established by natural language processing of clinical notes. Other risk factors and comorbidities were ascertained based on ICD-9-CM codes, medication use and laboratory data. ::: ::: Results: Of 1802 patients with an abnormal ABI, 115 had non-atherosclerotic vascular disease such as vasculitis, Buerger's disease, trauma and embolism (phenocopies) based on ICD-9-CM diagnosis codes and were excluded. The PAD cases (66±11 years, 64% men) were older than controls (61±8 years, 60% men) but had similar geographical distribution and ethnic composition. Among PAD cases, 1444 (85.6%) had an abnormal ABI, 233 (13.8%) had poorly compressible arteries and 10 (0.6%) had a history of lower extremity revascularization. In a random sample of 95 cases and 100 controls, risk factors and comorbidities ascertained from EMR-based algorithms had good concordance compared with manual record review; the precision ranged from 67% to 100% and recall from 84% to 100%. ::: ::: Conclusion: This study demonstrates use of the EMR to ascertain phenocopies, phenotype heterogeneity and relevant covariates to enable a GWAS of PAD. Biorepositories linked to EMR may provide a relatively efficient means of conducting GWAS.
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paper_title: Analysis of Biological Processes and Diseases Using Text Mining Approaches

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A number of biomedical text mining systems have been developed to extract biologically relevant information directly from the literature, complementing bioinformatics methods in the analysis of experimentally generated data. We provide a short overview of the general characteristics of natural language data, existing biomedical literature databases, and lexical resources relevant in the context of biomedical text mining. A selected number of practically useful systems are introduced together with the type of user queries supported and the results they generate. The extraction of biological relationships, such as protein–protein interactions as well as metabolic and signaling pathways using information extraction systems, will be discussed through example cases of cancer-relevant proteins. Basic strategies for detecting associations of genes to diseases together with literature mining of mutations, SNPs, and epigenetic information (methylation) are described. We provide an overview of disease-centric and gene-centric literature mining methods for linking genes to phenotypic and genotypic aspects. Moreover, we discuss recent efforts for finding biomarkers through text mining and for gene list analysis and prioritization. Some relevant issues for implementing a customized biomedical text mining system will be pointed out. To demonstrate the usefulness of literature mining for the molecular oncology domain, we implemented two cancer-related applications. The first tool consists of a literature mining system for retrieving human mutations together with supporting articles. Specific gene mutations are linked to a set of predefined cancer types. The second application consists of a text categorization system supporting breast cancerspecific literature search and document-based breast cancer gene ranking. Future trends in text mining emphasize the importance of community efforts such as the BioCreative challenge for the development and integration of multiple systems into a common platform provided by the BioCreative Metaserver.
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paper_title: Creation and implications of a phenome-genome network

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Although gene and protein measurements are increasing in quantity and comprehensiveness, they do not characterize a sample's entire phenotype in an environmental or experimental context. Here we comprehensively consider associations between components of phenotype, genotype and environment to identify genes that may govern phenotype and responses to the environment. Context from the annotations of gene expression data sets in the Gene Expression Omnibus is represented using the Unified Medical Language System, a compendium of biomedical vocabularies with nearly 1-million concepts. After showing how data sets can be clustered by annotative concepts, we find a network of relations between phenotypic, disease, environmental and experimental contexts as well as genes with differential expression associated with these concepts. We identify novel genes related to concepts such as aging. Comprehensively identifying genes related to phenotype and environment is a step toward the Human Phenome Project.
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paper_title: Generating genome-scale candidate gene lists for pharmacogenomics.

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A critical task in pharmacogenomics is identifying genes that may be important modulators of drug response. High-throughput experimental methods are often plagued by false positives and do not take advantage of existing knowledge. Candidate gene lists can usefully summarize existing knowledge, but they are expensive to generate manually and may therefore have incomplete coverage. We have developed a method that ranks 12,460 genes in the human genome on the basis of their potential relevance to a specific query drug and its putative indications. Our method uses known gene-drug interactions, networks of gene-gene interactions, and available measures of drug-drug similarity. It ranks genes by building a local network of known interactions and assessing the similarity of the query drug (by both structure and indication) with drugs that interact with gene products in the local network. In a comprehensive benchmark, our method achieves an overall area under the curve of 0.82. To showcase our method, we found novel gene candidates for warfarin, gefitinib, carboplatin, and gemcitabine, and we provide the molecular hypotheses for these predictions.
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paper_title: MedEx: a medication information extraction system for clinical narratives.

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Medication information is one of the most important types of clinical data in electronic medical records. It is critical for healthcare safety and quality, as well as for clinical research that uses electronic medical record data. However, medication data are often recorded in clinical notes as free-text. As such, they are not accessible to other computerized applications that rely on coded data. We describe a new natural language processing system (MedEx), which extracts medication information from clinical notes. MedEx was initially developed using discharge summaries. An evaluation using a data set of 50 discharge summaries showed it performed well on identifying not only drug names (F-measure 93.2%), but also signature information, such as strength, route, and frequency, with F-measures of 94.5%, 93.9%, and 96.0% respectively. We then applied MedEx unchanged to outpatient clinic visit notes. It performed similarly with F-measures over 90% on a set of 25 clinic visit notes.
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paper_title: STITCH: interaction networks of chemicals and proteins

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The knowledge about interactions between proteins and small molecules is essential for the understanding of molecular and cellular functions. However, information on such interactions is widely dispersed across numerous databases and the literature. To facilitate access to this data, STITCH ('search tool for interactions of chemicals') integrates information about interactions from metabolic pathways, crystal structures, binding experiments and drug-target relationships. Inferred information from phenotypic effects, text mining and chemical structure similarity is used to predict relations between chemicals. STITCH further allows exploring the network of chemical relations, also in the context of associated binding proteins. Each proposed interaction can be traced back to the original data sources. Our database contains interaction information for over 68,000 different chemicals, including 2200 drugs, and connects them to 1.5 million genes across 373 genomes and their interactions contained in the STRING database. STITCH is available at http://stitch.embl.de/.
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paper_title: Pharmspresso: a text mining tool for extraction of pharmacogenomic concepts and relationships from full text

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BackgroundPharmacogenomics studies the relationship between genetic variation and the variation in drug response phenotypes. The field is rapidly gaining importance: it promises drugs targeted to particular subpopulations based on genetic background. The pharmacogenomics literature has expanded rapidly, but is dispersed in many journals. It is challenging, therefore, to identify important associations between drugs and molecular entities – particularly genes and gene variants, and thus these critical connections are often lost. Text mining techniques can allow us to convert the free-style text to a computable, searchable format in which pharmacogenomic concepts (such as genes, drugs, polymorphisms, and diseases) are identified, and important links between these concepts are recorded. Availability of full text articles as input into text mining engines is key, as literature abstracts often do not contain sufficient information to identify these pharmacogenomic associations.ResultsThus, building on a tool called Textpresso, we have created the Pharmspresso tool to assist in identifying important pharmacogenomic facts in full text articles. Pharmspresso parses text to find references to human genes, polymorphisms, drugs and diseases and their relationships. It presents these as a series of marked-up text fragments, in which key concepts are visually highlighted. To evaluate Pharmspresso, we used a gold standard of 45 human-curated articles. Pharmspresso identified 78%, 61%, and 74% of target gene, polymorphism, and drug concepts, respectively.ConclusionPharmspresso is a text analysis tool that extracts pharmacogenomic concepts from the literature automatically and thus captures our current understanding of gene-drug interactions in a computable form. We have made Pharmspresso available at http://pharmspresso.stanford.edu.
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paper_title: Extracting and characterizing gene-drug relationships from the literature.

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A fundamental task of pharmacogenetics is to collect and classify relationships between genes and drugs. Currently, this useful information has not been comprehensively aggregated in any database and remains scattered throughout the published literature. Although there are efforts to collect this in
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paper_title: Textpresso: An Ontology-Based Information Retrieval and Extraction System for Biological Literature

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We have developed Textpresso, a new text-mining system for scientific literature whose capabilities go far beyond those of a simple keyword search engine. Textpresso's two major elements are a collection of the full text of scientific articles split into individual sentences, and the implementation of categories of terms for which a database of articles and individual sentences can be searched. The categories are classes of biological concepts (e.g., gene, allele, cell or cell group, phenotype, etc.) and classes that relate two objects (e.g., association, regulation, etc.) or describe one (e.g., biological process, etc.). Together they form a catalog of types of objects and concepts called an ontology. After this ontology is populated with terms, the whole corpus of articles and abstracts is marked up to identify terms of these categories. The current ontology comprises 33 categories of terms. A search engine enables the user to search for one or a combination of these tags and/or keywords within a sentence or document, and as the ontology allows word meaning to be queried, it is possible to formulate semantic queries. Full text access increases recall of biological data types from 45% to 95%. Extraction of particular biological facts, such as gene-gene interactions, can be accelerated significantly by ontologies, with Textpresso automatically performing nearly as well as expert curators to identify sentences; in searches for two uniquely named genes and an interaction term, the ontology confers a 3-fold increase of search efficiency. Textpresso currently focuses on Caenorhabditis elegans literature, with 3,800 full text articles and 16,000 abstracts. The lexicon of the ontology contains 14,500 entries, each of which includes all versions of a specific word or phrase, and it includes all categories of the Gene Ontology database. Textpresso is a useful curation tool, as well as search engine for researchers, and can readily be extended to other organism-specific corpora of text. Textpresso can be accessed at http://www.textpresso.org or via WormBase at http://www.wormbase.org.
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paper_title: Facilitating pharmacogenetic studies using electronic health records and natural-language processing: a case study of warfarin

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Objective DNA biobanks linked to comprehensive electronic health records systems are potentially powerful resources for pharmacogenetic studies. This study sought to develop natural-language-processing algorithms to extract drug-dose information from clinical text, and to assess the capabilities of such tools to automate the data-extraction process for pharmacogenetic studies. ::: ::: Materials and methods A manually validated warfarin pharmacogenetic study identified a cohort of 1125 patients with a stable warfarin dose, in which 776 patients were managed by Coumadin Clinic physicians, and the remaining 349 patients were managed by their providers. The authors developed two algorithms to extract weekly warfarin doses from both data sets: a regular expression-based program for semistructured Coumadin Clinic notes; and an advanced weekly dose calculator based on an existing medication information extraction system (MedEx) for narrative providers' notes. The authors then conducted an association analysis between an automatically extracted stable weekly dose of warfarin and four genetic variants of VKORC1 and CYP2C9 genes. The performance of the weekly dose-extraction program was evaluated by comparing it with a gold standard containing manually curated weekly doses. Precision, recall, F-measure, and overall accuracy were reported. Associations between known variants in VKORC1 and CYP2C9 and warfarin stable weekly dose were performed with linear regression adjusted for age, gender, and body mass index. ::: ::: Results The authors' evaluation showed that the MedEx-based system could determine patients' warfarin weekly doses with 99.7% recall, 90.8% precision, and 93.8% accuracy. Using the automatically extracted weekly doses of warfarin, the authors successfully replicated the previous known associations between warfarin stable dose and genetic variants in VKORC1 and CYP2C9 .
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paper_title: GenDrux: A biomedical literature search system to identify gene expression-based drug sensitivity in breast cancer

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Background ::: This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications.
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paper_title: 2010 i2b2/VA challenge on concepts, assertions, and relations in clinical text

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The 2010 i2b2/VA Workshop on Natural Language Processing Challenges for Clinical Records presented three tasks: a concept extraction task focused on the extraction of medical concepts from patient reports; an assertion classification task focused on assigning assertion types for medical problem concepts; and a relation classification task focused on assigning relation types that hold between medical problems, tests, and treatments. i2b2 and the VA provided an annotated reference standard corpus for the three tasks. Using this reference standard, 22 systems were developed for concept extraction, 21 for assertion classification, and 16 for relation classification. ::: ::: These systems showed that machine learning approaches could be augmented with rule-based systems to determine concepts, assertions, and relations. Depending on the task, the rule-based systems can either provide input for machine learning or post-process the output of machine learning. Ensembles of classifiers, information from unlabeled data, and external knowledge sources can help when the training data are inadequate.
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paper_title: Towards Internet-Age Pharmacovigilance: Extracting Adverse Drug Reactions from User Posts in Health-Related Social Networks

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Adverse reactions to drugs are among the most common causes of death in industrialized nations. Expensive clinical trials are not sufficient to uncover all of the adverse reactions a drug may cause, necessitating systems for post-marketing surveillance, or pharmacovigilance. These systems have typically relied on voluntary reporting by health care professionals. However, self-reported patient data has become an increasingly important resource, with efforts such as MedWatch from the FDA allowing reports directly from the consumer. In this paper, we propose mining the relationships between drugs and adverse reactions as reported by the patients themselves in user comments to health-related websites. We evaluate our system on a manually annotated set of user comments, with promising performance. We also report encouraging correlations between the frequency of adverse drug reactions found by our system in unlabeled data and the frequency of documented adverse drug reactions. We conclude that user comments pose a significant natural language processing challenge, but do contain useful extractable information which merits further exploration.
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paper_title: PhenoGO: Assigning Phenotypic Context to Gene Ontology Annotations with Natural Language Processing

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Natural language processing (NLP) is a high throughput technology because it can process vast quantities of text within a reasonable time period. It has the potential to substantially facilitate biomedical research by extracting, linking, and organizing massive amounts of information that occur in biomedical journal articles as well as in textual fields of biological databases. Until recently, much of the work in biological NLP and text mining has revolved around recognizing the occurrence of biomolecular entities in articles, and in extracting particular relationships among the entities. Now, researchers have recognized a need to link the extracted information to ontologies or knowledge bases, which is a more difficult task. One such knowledge base is Gene Ontology annotations (GOA), which significantly increases semantic computations over the function, cellular components and processes of genes. For multicellular organisms, these annotations can be refined with phenotypic context, such as the cell type, tissue, and organ because establishing phenotypic contexts in which a gene is expressed is a crucial step for understanding the development and the molecular underpinning of the pathophysiology of diseases. In this paper, we propose a system, PhenoGO, which automatically augments annotations in GOA with additional context. PhenoGO utilizes an existing NLP system, called BioMedLEE, an existing knowledge-based phenotype organizer system (PhenOS) in conjunction with MeSH indexing and established biomedical ontologies. More specifically, PhenoGO adds phenotypic contextual information to existing associations between gene products and GO terms as specified in GOA. The system also maps the context to identifiers that are associated with different biomedical ontologies, including the UMLS, Cell Ontology, Mouse Anatomy, NCBI taxonomy, GO, and Mammalian Phenotype Ontology. In addition, PhenoGO was evaluated for coding of anatomical and cellular information and assigning the coded phenotypes to the correct GOA; results obtained show that PhenoGO has a precision of 91% and recall of 92%, demonstrating that the PhenoGO NLP system can accurately encode a large number of anatomical and cellular ontologies to GO annotations. The PhenoGO Database may be accessed at the following URL: http://www.phenoGO.org
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paper_title: A context-blocks model for identifying clinical relationships in patient records

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Background ::: Patient records contain valuable information regarding explanation of diagnosis, progression of disease, prescription and/or effectiveness of treatment, and more. Automatic recognition of clinically important concepts and the identification of relationships between those concepts in patient records are preliminary steps for many important applications in medical informatics, ranging from quality of care to hypothesis generation.
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paper_title: Extraction of Adverse Drug Effects from Clinical Records

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With the rapidly growing use of electronic health records, the possibility of large-scale clinical information extraction has drawn much attention. We aim to extract adverse drug events and effects from records. As the first step of this challenge, this study assessed (1) how much adverse-effect information is contained in records, and (2) automatic extracting accuracy of the current standard Natural Language Processing (NLP) system. Results revealed that 7.7% of records include adverse event information, and that 59% of them (4.5% in total) can be extracted automatically. This result is particularly encouraging, considering the massive amounts of records, which are increasing daily.
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paper_title: A General Natural-language Text Processor for Clinical Radiology

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Objective : Development of a general natural-language processor that identifies clinical information in narrative reports and maps that information into a structured representation containing clinical terms. ::: ::: Design : The natural-language processor provides three phases of processing, all of which are driven by different knowledge sources. The first phase performs the parsing. It identifies the structure of the text through use of a grammar that defines semantic patterns and a target form. The second phase, regularization, standardizes the terms in the initial target structure via a compositional mapping of multi-word phrases. The third phase, encoding, maps the terms to a controlled vocabulary. Radiology is the test domain for the processor and the target structure is a formal model for representing clinical information in that domain. ::: ::: Measurements : The impression sections of 230 radiology reports were encoded by the processor. Results of an automated query of the resultant database for the occurrences of four diseases were compared with the analysis of a panel of three physicians to determine recall and precision. ::: ::: Results : Without training specific to the four diseases, recall and precision of the system(combined effect of the processor and query generator) were 70% and 87%. Training of the query component increased recall to 85% without changing precision.
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paper_title: Coding free text radiology reports using the Cancer Text Information Extraction System (caTIES).

paper_content:

We coded 700 radiology reports from 373 women using an unmodified deployment of the Cancer Text Information Extraction System (caTIES), a publicly-available tool using natural language processing techniques. We were moderately successfully using caTIES for case ascertainment, successfully identifying 9/11 of a random sample of cancer case (sensitivity 82%) and 5/100 controls (specificity 95%) We are currently developing a classification scheme to assess clinical risk of ovarian cancer and identifying required extensions to caTIES algorithms.
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paper_title: A side effect resource to capture phenotypic effects of drugs

paper_content:

The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research on this topic has been hampered by insufficient accessibility of data. Consequently, we have developed a public, computer-readable side effect resource (SIDER) that connects 888 drugs to 1450 side effect terms. It contains information on frequency in patients for one-third of the drug–side effect pairs. For 199 drugs, the side effect frequency of placebo administration could also be extracted. We illustrate the potential of SIDER with a number of analyses. The resource is freely available for academic research at http://sideeffects.embl.de.
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paper_title: Natural language processing to identify adverse drug events.

paper_content:

We tested and adapted Cancer Text Information Extraction System (caTIES), a publicly available natural language processing tool (NLP), as a method for identifying terms suggestive of adverse drug events (ADEs). Although caTIES was intended to extract concepts from surgical pathology reports, we report that it can successfully be used to search for ADEs on a much broader range of documents.
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paper_title: Classifying Semantic Relations In Bioscience Texts

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A crucial step toward the goal of automatic extraction of propositional information from natural language text is the identification of semantic relations between constituents in sentences. We examine the problem of distinguishing among seven relation types that can occur between the entities "treatment" and "disease" in bioscience text, and the problem of identifying such entities. We compare five generative graphical models and a neural network, using lexical, syntactic, and semantic features, finding that the latter help achieve high classification accuracy.
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paper_title: Active Computerized Pharmacovigilance Using Natural Language Processing, Statistics, and Electronic Health Records: A Feasibility Study

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OBJECTIVE It is vital to detect the full safety profile of a drug throughout its market life. Current pharmacovigilance systems still have substantial limitations, however. The objective of our work is to demonstrate the feasibility of using natural language processing (NLP), the comprehensive Electronic Health Record (EHR), and association statistics for pharmacovigilance purposes. DESIGN Narrative discharge summaries were collected from the Clinical Information System at New York Presbyterian Hospital (NYPH). MedLEE, an NLP system, was applied to the collection to identify medication events and entities which could be potential adverse drug events (ADEs). Co-occurrence statistics with adjusted volume tests were used to detect associations between the two types of entities, to calculate the strengths of the associations, and to determine their cutoff thresholds. Seven drugs/drug classes (ibuprofen, morphine, warfarin, bupropion, paroxetine, rosiglitazone, ACE inhibitors) with known ADEs were selected to evaluate the system. RESULTS One hundred thirty-two potential ADEs were found to be associated with the 7 drugs. Overall recall and precision were 0.75 and 0.31 for known ADEs respectively. Importantly, qualitative evaluation using historic roll back design suggested that novel ADEs could be detected using our system. CONCLUSIONS This study provides a framework for the development of active, high-throughput and prospective systems which could potentially unveil drug safety profiles throughout their entire market life. Our results demonstrate that the framework is feasible although there are some challenging issues. To the best of our knowledge, this is the first study using comprehensive unstructured data from the EHR for pharmacovigilance.
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paper_title: Extraction of semantic biomedical relations from text using conditional random fields

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BackgroundThe increasing amount of published literature in biomedicine represents an immense source of knowledge, which can only efficiently be accessed by a new generation of automated information extraction tools. Named entity recognition of well-defined objects, such as genes or proteins, has achieved a sufficient level of maturity such that it can form the basis for the next step: the extraction of relations that exist between the recognized entities. Whereas most early work focused on the mere detection of relations, the classification of the type of relation is also of great importance and this is the focus of this work. In this paper we describe an approach that extracts both the existence of a relation and its type. Our work is based on Conditional Random Fields, which have been applied with much success to the task of named entity recognition.ResultsWe benchmark our approach on two different tasks. The first task is the identification of semantic relations between diseases and treatments. The available data set consists of manually annotated PubMed abstracts. The second task is the identification of relations between genes and diseases from a set of concise phrases, so-called GeneRIF (Gene Reference Into Function) phrases. In our experimental setting, we do not assume that the entities are given, as is often the case in previous relation extraction work. Rather the extraction of the entities is solved as a subproblem. Compared with other state-of-the-art approaches, we achieve very competitive results on both data sets. To demonstrate the scalability of our solution, we apply our approach to the complete human GeneRIF database. The resulting gene-disease network contains 34758 semantic associations between 4939 genes and 1745 diseases. The gene-disease network is publicly available as a machine-readable RDF graph.ConclusionWe extend the framework of Conditional Random Fields towards the annotation of semantic relations from text and apply it to the biomedical domain. Our approach is based on a rich set of textual features and achieves a performance that is competitive to leading approaches. The model is quite general and can be extended to handle arbitrary biological entities and relation types. The resulting gene-disease network shows that the GeneRIF database provides a rich knowledge source for text mining. Current work is focused on improving the accuracy of detection of entities as well as entity boundaries, which will also greatly improve the relation extraction performance.
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paper_title: Integrating heterogeneous knowledge sources to acquire executable drug-related knowledge.

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Knowledge of medical entities, such as drug-related information is critical for many automated biomedical applications, such as decision support and pharmacovigilance. In this work, heterogeneous information sources were integrated automatically to obtain drug-related knowledge. We focus on one type of knowledge, drug-treats-condition, in the study and propose a framework for integrating disparate knowledge sources. Evaluation based on a random sample of drug-condition pairs indicated an overall coverage of 96%, recall of 98% and a precision of 87%. In conclusion, the preliminary study demonstrated that the knowledge generated from this study was comparable to the manually curated gold standard and that this method of automatically integrating knowledge sources is effective. The automated method should also be applicable to integrate other clinical knowledge, such as drug-related knowledge with omics information.
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paper_title: Automated Acquisition of Disease–Drug Knowledge from Biomedical and Clinical Documents: An Initial Study

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Objective: Explore the automated acquisition of knowledge in biomedical and clinical documents using text mining and statistical techniques to identify disease-drug associations. Design: Biomedical literature and clinical narratives from the patient record were mined to gather knowledge about disease-drug associations. Two NLP systems, BioMedLEE and MedLEE, were applied to Medline articles and discharge summaries, respectively. Disease and drug entities were identified using the NLP systems in addition to MeSH annotations for the Medline articles. Focusing on eight diseases, co-occurrence statistics were applied to compute and evaluate the strength of association between each disease and relevant drugs. Results: Ranked lists of disease-drug pairs were generated and cutoffs calculated for identifying stronger associations among these pairs for further analysis. Differences and similarities between the text sources (i.e., biomedical literature and patient record) and annotations (i.e., MeSH and NLP-extracted UMLS concepts) with regards to disease-drug knowledge were observed. Conclusion: This paper presents a method for acquiring disease-specific knowledge and a feasibility study of the method. The method is based on applying a combination of NLP and statistical techniques to both biomedical and clinical documents. The approach enabled extraction of knowledge about the drugs clinicians are using for patients with specific diseases based on the patient record, while it is also acquired knowledge of drugs frequently involved in controlled trials for those same diseases. In comparing the disease-drug associations, we found the results to be appropriate: the two text sources contained consistent as well as complementary knowledge, and manual review of the top five disease-drug associations by a medical expert supported their correctness across the diseases.
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paper_title: Mining electronic health records for adverse drug effects using regression based methods

paper_content:

The identification of post-marketed adverse drug events (ADEs) is paramount to health care. Spontaneous reporting systems (SRS) are currently the mainstay in pharmacovigilance. Recently, electronic health records (EHRs) have emerged as a promising and effective complementary resource to SRS, as they contain a more complete record of the patient, and do not suffer from the reporting biases inherent to SRS. However, mining EHRs for potential ADEs, which typically involves identification of statistical associations between drugs and medical conditions, introduced several other challenges, the main one being the necessity for statistical techniques that account for confounding. The objective of this paper is to present and demonstrate the feasibility of a method based on regression techniques, which is designed for automated large scale mining of ADEs in EHR narratives. To the best of our knowledge this is a first of its kind approach that combines both the use of EHR data, and regression based methods in order to address confounding and identify potential ADEs. Two separate experiments are conducted. The results, which are validated by clinical subject matter experts, demonstrate great promise, as well as highlight additional challenges.
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paper_title: Extracting Semantic Predications from Medline Citations for Pharmacogenomics

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We describe a natural language processing system (Enhanced SemRep) to identify core assertions on pharmacogenomics in Medline citations. Extracted information is represented as semantic predications covering a range of relations relevant to this domain. The specific relations addressed by the system provide greater precision than that achievable with methods that rely on entity co-occurrence. The development of Enhanced SemRep is based on the adaptation of an existing system and crucially depends on domain knowledge in the Unified Medical Language System. We provide a preliminary evaluation (55% recall and 73% precision) and discuss the potential of this system in assisting both clinical practice and scientific investigation.
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paper_title: Mining clinical relationships from patient narratives

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BackgroundThe Clinical E-Science Framework (CLEF) project has built a system to extract clinically significant information from the textual component of medical records in order to support clinical research, evidence-based healthcare and genotype-meets-phenotype informatics. One part of this system is the identification of relationships between clinically important entities in the text. Typical approaches to relationship extraction in this domain have used full parses, domain-specific grammars, and large knowledge bases encoding domain knowledge. In other areas of biomedical NLP, statistical machine learning (ML) approaches are now routinely applied to relationship extraction. We report on the novel application of these statistical techniques to the extraction of clinical relationships.ResultsWe have designed and implemented an ML-based system for relation extraction, using support vector machines, and trained and tested it on a corpus of oncology narratives hand-annotated with clinically important relationships. Over a class of seven relation types, the system achieves an average F1 score of 72%, only slightly behind an indicative measure of human inter annotator agreement on the same task. We investigate the effectiveness of different features for this task, how extraction performance varies between inter- and intra-sentential relationships, and examine the amount of training data needed to learn various relationships.ConclusionWe have shown that it is possible to extract important clinical relationships from text, using supervised statistical ML techniques, at levels of accuracy approaching those of human annotators. Given the importance of relation extraction as an enabling technology for text mining and given also the ready adaptability of systems based on our supervised learning approach to other clinical relationship extraction tasks, this result has significance for clinical text mining more generally, though further work to confirm our encouraging results should be carried out on a larger sample of narratives and relationship types.
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paper_title: Synthesis of Pharmacokinetic Pathways through Knowledge Acquisition and Automated Reasoning

paper_content:

Biological pathways are seen as highly critical in our understanding of the mechanism of biological functions. To collect information about pathways, manual curation has been the most popular method. However, pathway annotation is regarded as heavily timeconsuming, as it requires expert curators to identify and collect information from different sources. Even with the pieces of biological facts and interactions collected from various sources, curators have to apply their biological knowledge to arrange the acquired interactions in such a way that together they perform a common biological function as a pathway. In this paper, we propose a novel approach for automated pathway synthesis that acquires facts from hand-curated knowledge bases. To comprehend the incompleteness of the knowledge bases, our approach also obtains facts through automated extraction from Medline abstracts. An essential component of our approach is to apply logical reasoning to the acquired facts based on the biological knowledge about pathways. By representing such biological knowledge, the reasoning component is capable of assigning ordering to the acquired facts and interactions that is necessary for pathway synthesis. We demonstrate the feasibility of our approach with the development of a system that synthesizes pharmacokinetic pathways. We evaluate our approach by reconstructing the existing pharmacokinetic pathways available in PharmGKB. Our results show that not only that our approach is capable of synthesizing these pathways but also uncovering information that is not available in the manually annotated pathways.
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paper_title: Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases

paper_content:

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs.
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paper_title: Mining connections between chemicals, proteins, and diseases extracted from Medline annotations

paper_content:

The biomedical literature is an important source of information about the biological activity and effects of chemicals. We present an application that extracts terms indicating biological activity of chemicals from Medline records, associates them with chemical name and stores the terms in a repository called ChemoText. We describe the construction of ChemoText and then demonstrate its utility in drug research by employing Swanson's ABC discovery paradigm. We reproduce Swanson's discovery of a connection between magnesium and migraine in a novel approach that uses only proteins as the intermediate B terms. We validate our methods by using a cutoff date and evaluate them by calculating precision and recall. In addition to magnesium, we have identified valproic acid and nitric oxide as chemicals which developed links to migraine. We hypothesize, based on protein annotations, that zinc and retinoic acid may play a role in migraine. The ChemoText repository has promise as a data source for drug discovery.
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paper_title: Gene mention normalization and interaction extraction with context models and sentence motifs

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Background:The goal of text mining is to make the information conveyed in scientific publications accessible to structured search and automatic analysis. Two important subtasks of text mining are entity mention normalization - to identify biomedical objects in text - and extraction of qualified relationships between those objects. We describe a method for identifying genes and relationships between proteins.Results:We present solutions to gene mention normalization and extraction of protein-protein interactions. For the first task, we identify genes by using background knowledge on each gene, namely annotations related to function, location, disease, and so on. Our approach currently achieves an f-measure of 86.4% on the BioCreative II gene normalization data. For the extraction of protein-protein interactions, we pursue an approach that builds on classical sequence analysis: motifs derived from multiple sequence alignments. The method achieves an f-measure of 24.4% (micro-average) in the BioCreative II interaction pair subtask.Conclusion:For gene mention normalization, our approach outperforms strategies that utilize only the matching of genes names against dictionaries, without invoking further knowledge on each gene. Motifs derived from alignments of sentences are successful at identifying protein interactions in text; the approach we present in this report is fully automated and performs similarly to systems that require human intervention at one or more stages.Availability:Our methods for gene, protein, and species identification, and extraction of protein-protein are available as part of the BioCreative Meta Services (BCMS), see http://bcms.bioinfo.cnio.es/.
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paper_title: Edgar: Extraction of drugs, genes and relations from the biomedical literature

paper_content:

EDGAR (Extraction of Drugs, Genes and Relations) is a natural language processing system that extracts information about drugs and genes relevant to cancer from the biomedical literature. This automatically extracted information has remarkable potential to facilitate computational analysis in the molecular biology of cancer, and the technology is straightforwardly generalizable to many areas of biomedicine. This paper reports on the mechanisms for automatically generating such assertions and on a simple application, conceptual clustering of documents. The system uses a stochastic part of speech tagger, generates an underspecified syntactic parse and then uses semantic and pragmatic information to construct its assertions. The system builds on two important existing resources: the MEDLINE database of biomedical citations and abstracts and the Unified Medical Language System, which provides syntactic and semantic information about the terms found in biomedical abstracts.
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paper_title: Synthesis of Pharmacokinetic Pathways through Knowledge Acquisition and Automated Reasoning

paper_content:

Biological pathways are seen as highly critical in our understanding of the mechanism of biological functions. To collect information about pathways, manual curation has been the most popular method. However, pathway annotation is regarded as heavily timeconsuming, as it requires expert curators to identify and collect information from different sources. Even with the pieces of biological facts and interactions collected from various sources, curators have to apply their biological knowledge to arrange the acquired interactions in such a way that together they perform a common biological function as a pathway. In this paper, we propose a novel approach for automated pathway synthesis that acquires facts from hand-curated knowledge bases. To comprehend the incompleteness of the knowledge bases, our approach also obtains facts through automated extraction from Medline abstracts. An essential component of our approach is to apply logical reasoning to the acquired facts based on the biological knowledge about pathways. By representing such biological knowledge, the reasoning component is capable of assigning ordering to the acquired facts and interactions that is necessary for pathway synthesis. We demonstrate the feasibility of our approach with the development of a system that synthesizes pharmacokinetic pathways. We evaluate our approach by reconstructing the existing pharmacokinetic pathways available in PharmGKB. Our results show that not only that our approach is capable of synthesizing these pathways but also uncovering information that is not available in the manually annotated pathways.
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paper_title: Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases

paper_content:

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs.
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paper_title: Text mining: Generating hypotheses from MEDLINE

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Hypothesis generation, a crucial initial step for making scientific discoveries, relies on prior knowledge, experience, and intuition. Chance connections made between seemingly distinct subareas sometimes turn out to be fruitful. The goal in text mining is to assist in this process by automatically discovering a small set of interesting hypotheses from a suitable text collection. In this report, we present open and closed text mining algorithms that are built within the discovery framework established by Swanson and Smalheiser. Our algorithms represent topics using metadata profiles. When applied to MEDLINE, these are MeSH based profiles. We present experiments that demonstrate the effectiveness of our algorithms. Specifically, our algorithms successfully generate ranked term lists where the key terms representing novel relationships between topics are ranked high.
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paper_title: Ontology-guided data preparation for discovering genotype-phenotype relationships

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BackgroundComplexity and amount of post-genomic data constitute two major factors limiting the application of Knowledge Discovery in Databases (KDD) methods in life sciences. Bio-ontologies may nowadays play key roles in knowledge discovery in life science providing semantics to data and to extracted units, by taking advantage of the progress of Semantic Web technologies concerning the understanding and availability of tools for knowledge representation, extraction, and reasoning.ResultsThis paper presents a method that exploits bio-ontologies for guiding data selection within the preparation step of the KDD process. We propose three scenarios in which domain knowledge and ontology elements such as subsumption, properties, class descriptions, are taken into account for data selection, before the data mining step. Each of these scenarios is illustrated within a case-study relative to the search of genotype-phenotype relationships in a familial hypercholesterolemia dataset. The guiding of data selection based on domain knowledge is analysed and shows a direct influence on the volume and significance of the data mining results.ConclusionsThe method proposed in this paper is an efficient alternative to numerical methods for data selection based on domain knowledge. In turn, the results of this study may be reused in ontology modelling and data integration.
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paper_title: Mining MEDLINE for implicit links between dietary substances and diseases

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Motivation: Text mining systems aim at knowledge discovery from text collections. This work presents our text mining algorithm and demonstrates its use to uncover information that could form the basis of new hypotheses. In particular, we use it to discover novel uses for Curcuma longa, a dietary substance, which is highly regarded for its therapeutic properties in Asia. ::: ::: Results: Several disease were identified that offer novel research contexts for curcumin. We analyze select suggestions, such as retinal diseases, Crohn's disease and disorders related to the spinal cord. Our analysis suggests that there is strong evidence in favor of a beneficial role for curcumin in these diseases. The evidence is based on curcumin's influence on several genes, such as COX-2, TNF-alpha, JNK, p38 MAPK and TGF-beta. This research suggests that our discovery algorithm may be used to suggest novel uses for dietary and pharmacological substances. More generally, our text mining algorithm may be used to uncover information that potentially sheds new light on a given topic of interest. ::: ::: Availability: Contact authors.
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paper_title: Discovering drug–drug interactions: a text-mining and reasoning approach based on properties of drug metabolism

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Motivation: Identifying drug–drug interactions (DDIs) is a critical process in drug administration and drug development. Clinical support tools often provide comprehensive lists of DDIs, but they usually lack the supporting scientific evidences and different tools can return inconsistent results. In this article, we propose a novel approach that integrates text mining and automated reasoning to derive DDIs. Through the extraction of various facts of drug metabolism, not only the DDIs that are explicitly mentioned in text can be extracted but also the potential interactions that can be inferred by reasoning. ::: ::: Results: Our approach was able to find several potential DDIs that are not present in DrugBank. We manually evaluated these interactions based on their supporting evidences, and our analysis revealed that 81.3% of these interactions are determined to be correct. This suggests that our approach can uncover potential DDIs with scientific evidences explaining the mechanism of the interactions. ::: ::: Contact: luis.tari@roche.com
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paper_title: Conceptual biology, hypothesis discovery, and text mining: Swanson's legacy

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Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.
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paper_title: Abductive reasoning: Logic, visual thinking, and coherence

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This paper discusses abductive reasoning—that is, reasoning in which explanatory hypotheses are formed and evaluated. First, it criticizes two recent formal logical models of abduction. An adequate formalization would have to take into account the following aspects of abduction: explanation is not deduction; hypotheses are layered; abduction is sometimes creative; hypotheses may be revolutionary; completeness is elusive; simplicity is complex; and abductive reasoning may be visual and non-sentential. Second, in order to illustrate visual aspects of hypothesis formation, the paper describes recent work on visual inference in archaeology. Third, in connection with the evaluation of explanatory hypotheses, the paper describes recent results on the computation of coherence.
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paper_title: Inference for bio-IE: GENIA meets EKOSS

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Information extraction for molecular biology (bioIE) aims to find useful pieces of bio-molecular knowledge (bio-knowledge, hereafter) from natural language expressions in the literature, and to store them in a structured form accessible by computers. One example is protein-protein interaction (PPI) extraction (Bunescu et al., 2004), which has long been a primary task of bio-IE. Usually, a PPI is expressed by a pair of proteins. For example, from the text, “Secretion of TNF was abolished by BHA · · ·,” the following PPI can be extracted:
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paper_title: Data Mining: Practical Machine Learning Tools and Techniques

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Data Mining: Practical Machine Learning Tools and Techniques offers a thorough grounding in machine learning concepts as well as practical advice on applying machine learning tools and techniques in real-world data mining situations. This highly anticipated third edition of the most acclaimed work on data mining and machine learning will teach you everything you need to know about preparing inputs, interpreting outputs, evaluating results, and the algorithmic methods at the heart of successful data mining. Thorough updates reflect the technical changes and modernizations that have taken place in the field since the last edition, including new material on Data Transformations, Ensemble Learning, Massive Data Sets, Multi-instance Learning, plus a new version of the popular Weka machine learning software developed by the authors. Witten, Frank, and Hall include both tried-and-true techniques of today as well as methods at the leading edge of contemporary research. *Provides a thorough grounding in machine learning concepts as well as practical advice on applying the tools and techniques to your data mining projects *Offers concrete tips and techniques for performance improvement that work by transforming the input or output in machine learning methods *Includes downloadable Weka software toolkit, a collection of machine learning algorithms for data mining tasks-in an updated, interactive interface. Algorithms in toolkit cover: data pre-processing, classification, regression, clustering, association rules, visualization
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paper_title: An Automated Approach to Mapping External Terminologies to the UMLS

paper_content:

Nowadays, providing interoperability between different biomedical terminologies is a critical issue for efficient information sharing. One problem making interoperability difficult is the lack of automated methods simplifying the mapping process. In this study, we propose an automated approach to mapping external terminologies to the Unified Medical Language System (UMLS). Our approach applies a sequential combination of two basic matching methods classically used in ontology matching. First, a lexical technique identifies similar strings between the external terminology and the UMLS. Second, a structure-based technique validates, in part, the lexical alignmentby computing paths to top-level concepts and checking the compatibility of these top-level concepts across the external terminology and the UMLS. The method was applied to the mapping of the large-scale biomedical thesaurus EMTREE to the complete UMLS Metathesaurus. In total, 47.9% coverage of EMTREE terms was reached, leading to 80% coverage of EMTREE concepts. Our method has revealed a high compatibility in 6 out of 15 top-level categories across terminologies. The validation of lexical mappings ranges over 75.8% of the total lexical alignment. Overall, the method rules out a total of 6927 (7.9%) lexical mappings, with a global precision of 78%.
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paper_title: Assessment of NER solutions against the first and second CALBC Silver Standard Corpus

paper_content:

Background: Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. Results: All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided preannotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I. The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants’ solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PRGE.
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paper_title: Using Medical Text Extraction, Reasoning and Mapping System (MTERMS) to process medication information in outpatient clinical notes.

paper_content:

Clinical information is often coded using different terminologies, and therefore is not interoperable. Our goal is to develop a general natural language processing (NLP) system, called Medical Text Extraction, Reasoning and Mapping System (MTERMS), which encodes clinical text using different terminologies and simultaneously establishes dynamic mappings between them. MTERMS applies a modular, pipeline approach flowing from a preprocessor, semantic tagger, terminology mapper, context analyzer, and parser to structure inputted clinical notes. Evaluators manually reviewed 30 free-text and 10 structured outpatient clinical notes compared to MTERMS output. MTERMS achieved an overall F-measure of 90.6 and 94.0 for free-text and structured notes respectively for medication and temporal information. The local medication terminology had 83.0% coverage compared to RxNorm’s 98.0% coverage for free-text notes. 61.6% of mappings between the terminologies are exact match. Capture of duration was significantly improved (91.7% vs. 52.5%) from systems in the third i2b2 challenge.
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paper_title: Natural language processing: an introduction

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Objectives To provide an overview and tutorial of natural language processing (NLP) and modern NLP-system design. Target audience This tutorial targets the medical informatics generalist who has limited acquaintance with the principles behind NLP and/or limited knowledge of the current state of the art. Scope We describe the historical evolution of NLP, and summarize common NLP sub-problems in this extensive field. We then provide a synopsis of selected highlights of medical NLP efforts. After providing a brief description of common machine-learning approaches that are being used for diverse NLP sub-problems, we discuss how modern NLP architectures are designed, with a summary of the Apache Foundation’s Unstructured Information Management Architecture. We finally consider possible future directions for NLP, and reflect on the possible impact of IBM Watson on the medical field.
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paper_title: INTRODUCTION TO MACHINE LEARNINGIntroduction to Machine Learning

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This chapter introduces the foundations of machine learning that are necessary to motivate its combination to evolutionary algorithms and image processing. In the chapter, we will describe several machine learning tools, suitable for a wide variety of data and tasks. The goal is not to describe the total number of techniques, but instead to present a general view of the field through the description of the mail problems considered in machine learning.
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paper_title: The CALBC Silver Standard Corpus - Harmonizing multiple semantic annotations in a large biomedical corpus

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The CALBC initiative aims to provide a large-scale biomedical text corpus that contains semantic annotations for tagged named entities of different kinds. The generation of this corpus requires that the annotations from different automatic annotation systems are harmonized. In the first phase, the annotation systems from 5 participants (EMBL-EBI, EMC Rotterdam, NLM, JULIE Lab Jena, and Linguamatics) were gathered. All annotations were delivered in a common annotation format that included concept ids in the boundary assignments and that enabled comparison and alignment of the results. During the harmonization phase, the produced results from different systems have been integrated into a single harmonised corpus (“silver standard” corpus) by applying a voting scheme. We give an overview of the processed data and the principles of harmonization – formal boundary reconciliation and semantic matching of named entities. Finally all submissions of the participants have been evaluated against the silver standard corpus. We found that species and disease annotations are better standardised amongst the partners than the annotations of genes and proteins. The raw corpus is now available for additional named entity annotations. Part of the annotated corpus will be made available later for a public challenge. We expect that we can improve corpus building activities both in terms of the numbers of named entity classes being covered, as well as the size of the corpus in terms of annotated documents.
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paper_title: Inter-Coder Agreement for Computational Linguistics

paper_content:

This article is a survey of methods for measuring agreement among corpus annotators. It exposes the mathematics and underlying assumptions of agreement coefficients, covering Krippendorff's alpha as well as Scott's pi and Cohen's kappa; discusses the use of coefficients in several annotation tasks; and argues that weighted, alpha-like coefficients, traditionally less used than kappa-like measures in computational linguistics, may be more appropriate for many corpus annotation tasks---but that their use makes the interpretation of the value of the coefficient even harder.
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paper_title: An Approach to Text Corpus Construction which Cuts Annotation Costs and Maintains Reusability of Annotated Data

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We consider the impact Active Learning (AL) has on effective and efficient text corpus annotation, and report on reduction rates for annotation efforts ranging up until 72%. We also address the issue whether a corpus annotated by means of AL ‐ using a particular classifier and a particular feature set ‐ can be re-used to train classifiers different from the ones employed by AL, supplying alternative feature sets as well. We, finally, report on our experience with the AL paradigm under real-world conditions, i.e., the annotation of large-scale document corpora for the life sciences.
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paper_title: Assessment of NER solutions against the first and second CALBC Silver Standard Corpus

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Background: Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. Results: All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided preannotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I. The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants’ solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PRGE.
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paper_title: Interval estimation for Cohen's kappa as a measure of agreement.

paper_content:

Cohen's kappa statistic is a very well known measure of agreement between two raters with respect to a dichotomous outcome. Several expressions for its asymptotic variance have been derived and the normal approximation to its distribution has been used to construct confidence intervals. However, information on the accuracy of these normal-approximation confidence intervals is not comprehensive. Under the common correlation model for dichotomous data, we evaluate 95 per cent lower confidence bounds constructed using four asymptotic variance expressions. Exact computation, rather than simulation is employed. Specific conditions under which the use of asymptotic variance formulae is reasonable are determined.
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paper_title: Assessing Agreement On Classification Tasks: The Kappa Statistic

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Currently, computational linguists and cognitive scientists working in the area of discourse and dialogue argue that their subjective judgments are reliable using several different statistics, none of which are easily interpretable or comparable to each other. Meanwhile, researchers in content analysis have already experienced the same difficulties and come up with a solution in the kappa statistic. We discuss what is wrong with reliability measures as they are currently used for discourse and dialogue work in computational linguistics and cognitive science, and argue that we would be better off as a field adopting techniques from content analysis.
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paper_title: A probabilistic interpretation of precision, recall and F-score, with implication for evaluation

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We address the problems of 1/ assessing the confidence of the standard point estimates, precision, recall and F-score, and 2/ comparing the results, in terms of precision, recall and F-score, obtained using two different methods. To do so, we use a probabilistic setting which allows us to obtain posterior distributions on these performance indicators, rather than point estimates. This framework is applied to the case where different methods are run on different datasets from the same source, as well as the standard situation where competing results are obtained on the same data.
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paper_title: Knowtator: A Protege Plug-In For Annotated Corpus Construction

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A general-purpose text annotation tool called Knowtator is introduced. Knowtator facilitates the manual creation of annotated corpora that can be used for evaluating or training a variety of natural language processing systems. Building on the strengths of the widely used Protege knowledge representation system, Knowtator has been developed as a Protege plug-in that leverages Protege's knowledge representation capabilities to specify annotation schemas. Knowtator's unique advantage over other annotation tools is the ease with which complex annotation schemas (e.g. schemas which have constrained relationships between annotation types) can be defined and incorporated into use. Knowtator is available under the Mozilla Public License 1.1 at http://bionlp.sourceforge.net/Knowtator.
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paper_title: New directions in biomedical text annotation: definitions, guidelines and corpus construction

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BackgroundWhile biomedical text mining is emerging as an important research area, practical results have proven difficult to achieve. We believe that an important first step towards more accurate text-mining lies in the ability to identify and characterize text that satisfies various types of information needs. We report here the results of our inquiry into properties of scientific text that have sufficient generality to transcend the confines of a narrow subject area, while supporting practical mining of text for factual information. Our ultimate goal is to annotate a significant corpus of biomedical text and train machine learning methods to automatically categorize such text along certain dimensions that we have defined.ResultsWe have identified five qualitative dimensions that we believe characterize a broad range of scientific sentences, and are therefore useful for supporting a general approach to text-mining: focus, polarity, certainty, evidence, and directionality. We define these dimensions and describe the guidelines we have developed for annotating text with regard to them.To examine the effectiveness of the guidelines, twelve annotators independently annotated the same set of 101 sentences that were randomly selected from current biomedical periodicals. Analysis of these annotations shows 70–80% inter-annotator agreement, suggesting that our guidelines indeed present a well-defined, executable and reproducible task.ConclusionWe present our guidelines defining a text annotation task, along with annotation results from multiple independently produced annotations, demonstrating the feasibility of the task. The annotation of a very large corpus of documents along these guidelines is currently ongoing. These annotations form the basis for the categorization of text along multiple dimensions, to support viable text mining for experimental results, methodology statements, and other forms of information. We are currently developing machine learning methods, to be trained and tested on the annotated corpus, that would allow for the automatic categorization of biomedical text along the general dimensions that we have presented. The guidelines in full detail, along with annotated examples, are publicly available.
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paper_title: Constructing Biological Knowledge Bases by Extracting Information from Text Sources

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Recently, there has been much effort in making databases for Inolecular biology more accessible osld interoperable. However, information in text. form, such as MEDLINE records, remains a greatly underutilized source of biological information. We have begun a research effort aimed at automatically mapping information from text. sources into structured representations, such as knowledge bases. Our approach to this task is to use machine-learning methods to induce routines for extracting facts from text. We describe two learning methods that we have applied to this task -a statistical text classification method, and a relational learning method -and our initial experiments in learning such information-extraction routines. We also present an approach to decreasing the cost of learning information-extraction routines by learning from "weakly" labeled training data.
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paper_title: The CALBC Silver Standard Corpus - Harmonizing multiple semantic annotations in a large biomedical corpus

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The CALBC initiative aims to provide a large-scale biomedical text corpus that contains semantic annotations for tagged named entities of different kinds. The generation of this corpus requires that the annotations from different automatic annotation systems are harmonized. In the first phase, the annotation systems from 5 participants (EMBL-EBI, EMC Rotterdam, NLM, JULIE Lab Jena, and Linguamatics) were gathered. All annotations were delivered in a common annotation format that included concept ids in the boundary assignments and that enabled comparison and alignment of the results. During the harmonization phase, the produced results from different systems have been integrated into a single harmonised corpus (“silver standard” corpus) by applying a voting scheme. We give an overview of the processed data and the principles of harmonization – formal boundary reconciliation and semantic matching of named entities. Finally all submissions of the participants have been evaluated against the silver standard corpus. We found that species and disease annotations are better standardised amongst the partners than the annotations of genes and proteins. The raw corpus is now available for additional named entity annotations. Part of the annotated corpus will be made available later for a public challenge. We expect that we can improve corpus building activities both in terms of the numbers of named entity classes being covered, as well as the size of the corpus in terms of annotated documents.
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paper_title: The Specification Language TimeML

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In this paper we provide a description of TimeML, a rich specification language for event and temporal expressions in natural language text, developed in the context of the AQUAINT program on Question Answering Systems. Unlike most previous work on event annotation, TimeML captures three distinct phenomena in temporal markup: (1) it systematically anchors event predicates to a broad range of temporally denotating expressions; (2) it orders event expressions in text relative to one another, both intrasententially and in discourse; and (3) it allows for a delayed (underspecified) interpretation of partially determined temporal expressions. We demonstrate the expressiveness of TimeML for a broad range of syntactic and semantic contexts, including aspectual predication, modal subordination, and an initial treatment of lexical and constructional causation in text.
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paper_title: 2010 i2b2/VA challenge on concepts, assertions, and relations in clinical text

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The 2010 i2b2/VA Workshop on Natural Language Processing Challenges for Clinical Records presented three tasks: a concept extraction task focused on the extraction of medical concepts from patient reports; an assertion classification task focused on assigning assertion types for medical problem concepts; and a relation classification task focused on assigning relation types that hold between medical problems, tests, and treatments. i2b2 and the VA provided an annotated reference standard corpus for the three tasks. Using this reference standard, 22 systems were developed for concept extraction, 21 for assertion classification, and 16 for relation classification. ::: ::: These systems showed that machine learning approaches could be augmented with rule-based systems to determine concepts, assertions, and relations. Depending on the task, the rule-based systems can either provide input for machine learning or post-process the output of machine learning. Ensembles of classifiers, information from unlabeled data, and external knowledge sources can help when the training data are inadequate.
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paper_title: Corpus annotation for mining biomedical events from literature

paper_content:

BackgroundAdvanced Text Mining (TM) such as semantic enrichment of papers, event or relation extraction, and intelligent Question Answering have increasingly attracted attention in the bio-medical domain. For such attempts to succeed, text annotation from the biological point of view is indispensable. However, due to the complexity of the task, semantic annotation has never been tried on a large scale, apart from relatively simple term annotation.ResultsWe have completed a new type of semantic annotation, event annotation, which is an addition to the existing annotations in the GENIA corpus. The corpus has already been annotated with POS (Parts of Speech), syntactic trees, terms, etc. The new annotation was made on half of the GENIA corpus, consisting of 1,000 Medline abstracts. It contains 9,372 sentences in which 36,114 events are identified. The major challenges during event annotation were (1) to design a scheme of annotation which meets specific requirements of text annotation, (2) to achieve biology-oriented annotation which reflect biologists' interpretation of text, and (3) to ensure the homogeneity of annotation quality across annotators. To meet these challenges, we introduced new concepts such as Single-facet Annotation and Semantic Typing, which have collectively contributed to successful completion of a large scale annotation.ConclusionThe resulting event-annotated corpus is the largest and one of the best in quality among similar annotation efforts. We expect it to become a valuable resource for NLP (Natural Language Processing)-based TM in the bio-medical domain.
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paper_title: The GeneReg Corpus for Gene Expression Regulation Events - An Overview of the Corpus and its In-Domain and Out-of-Domain Interoperability.

paper_content:

Despite the large variety of corpora in the biomedical domain their annotations differ in many respects, e.g., the coverage of different, highly specialized knowledge domains, varying degrees of granularity of the targeted relations, the specificity of linguistic grounding of relations and named entities referred to in the documents, etc. We here introduce GENEREG (Gene Regulation Corpus), the result of an annotation campaign led by the Jena University Language & Information Engineering (JULIE) Lab. The GENEREG corpus consists of 314 abstracts dealing with the regulation of gene expression in the model organism E. coli. Our emphasis in this paper is on the compatibility and, thus, linkage, of the GENEREG corpus with the alternative GENIA event corpus and with several in-domain and out-of-domain lexical resources, e.g., the SPECIALIST LEXICON, FRAMENET, and WORDNET. The links we established from the GENEREG corpus to these external resources will help improve the performance of the automatic relation extraction engine JREX trained and evaluated on GENEREG.
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paper_title: Construction of an annotated corpus to support biomedical information extraction

paper_content:

Background ::: Information Extraction (IE) is a component of text mining that facilitates knowledge discovery by automatically locating instances of interesting biomedical events from huge document collections. As events are usually centred on verbs and nominalised verbs, understanding the syntactic and semantic behaviour of these words is highly important. Corpora annotated with information concerning this behaviour can constitute a valuable resource in the training of IE components and resources.
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paper_title: Assessment of disease named entity recognition on a corpus of annotated sentences

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BackgroundIn recent years, the recognition of semantic types from the biomedical scientific literature has been focused on named entities like protein and gene names (PGNs) and gene ontology terms (GO terms). Other semantic types like diseases have not received the same level of attention. Different solutions have been proposed to identify disease named entities in the scientific literature. While matching the terminology with language patterns suffers from low recall (e.g., Whatizit) other solutions make use of morpho-syntactic features to better cover the full scope of terminological variability (e.g., MetaMap). Currently, MetaMap that is provided from the National Library of Medicine (NLM) is the state of the art solution for the annotation of concepts from UMLS (Unified Medical Language System) in the literature. Nonetheless, its performance has not yet been assessed on an annotated corpus. In addition, little effort has been invested so far to generate an annotated dataset that links disease entities in text to disease entries in a database, thesaurus or ontology and that could serve as a gold standard to benchmark text mining solutions.ResultsAs part of our research work, we have taken a corpus that has been delivered in the past for the identification of associations of genes to diseases based on the UMLS Metathesaurus and we have reprocessed and re-annotated the corpus. We have gathered annotations for disease entities from two curators, analyzed their disagreement (0.51 in the kappa-statistic) and composed a single annotated corpus for public use. Thereafter, three solutions for disease named entity recognition including MetaMap have been applied to the corpus to automatically annotate it with UMLS Metathesaurus concepts. The resulting annotations have been benchmarked to compare their performance.ConclusionsThe annotated corpus is publicly available at ftp://ftp.ebi.ac.uk/pub/software/textmining/corpora/diseasesand can serve as a benchmark to other systems. In addition, we found that dictionary look-up already provides competitive results indicating that the use of disease terminology is highly standardized throughout the terminologies and the literature. MetaMap generates precise results at the expense of insufficient recall while our statistical method obtains better recall at a lower precision rate. Even better results in terms of precision are achieved by combining at least two of the three methods leading, but this approach again lowers recall. Altogether, our analysis gives a better understanding of the complexity of disease annotations in the literature. MetaMap and the dictionary based approach are available through the Whatizit web service infrastructure (Rebholz-Schuhmann D, Arregui M, Gaudan S, Kirsch H, Jimeno A: Text processing through Web services: Calling Whatizit. Bioinformatics 2008, 24:296-298).
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paper_title: Collaborative text-annotation resource for disease-centered relation extraction from biomedical text

paper_content:

Agglomerating results from studies of individual biological components has shown the potential to produce biomedical discovery and the promise of therapeutic development. Such knowledge integration could be tremendously facilitated by automated text mining for relation extraction in the biomedical literature. Relation extraction systems cannot be developed without substantial datasets annotated with ground truth for benchmarking and training. The creation of such datasets is hampered by the absence of a resource for launching a distributed annotation effort, as well as by the lack of a standardized annotation schema. We have developed an annotation schema and an annotation tool which can be widely adopted so that the resulting annotated corpora from a multitude of disease studies could be assembled into a unified benchmark dataset. The contribution of this paper is threefold. First, we provide an overview of available benchmark corpora and derive a simple annotation schema for specific binary relation extraction problems such as protein-protein and gene-disease relation extraction. Second, we present BioNotate: an open source annotation resource for the distributed creation of a large corpus. Third, we present and make available the results of a pilot annotation effort of the autism disease network.
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paper_title: Machine-learned solutions for three stages of clinical information extraction: the state of the art at i2b2 2010

paper_content:

Objective As clinical text mining continues to mature, its potential as an enabling technology for innovations in patient care and clinical research is becoming a reality. A critical part of that process is rigid benchmark testing of natural language processing methods on realistic clinical narrative. In this paper, the authors describe the design and performance of three state-of-the-art text-mining applications from the National Research Council of Canada on evaluations within the 2010 i2b2 challenge. ::: ::: Design The three systems perform three key steps in clinical information extraction: (1) extraction of medical problems, tests, and treatments, from discharge summaries and progress notes; (2) classification of assertions made on the medical problems; (3) classification of relations between medical concepts. Machine learning systems performed these tasks using large-dimensional bags of features, as derived from both the text itself and from external sources: UMLS, cTAKES, and Medline. ::: ::: Measurements Performance was measured per subtask, using micro-averaged F-scores, as calculated by comparing system annotations with ground-truth annotations on a test set. ::: ::: Results The systems ranked high among all submitted systems in the competition, with the following F-scores: concept extraction 0.8523 (ranked first); assertion detection 0.9362 (ranked first); relationship detection 0.7313 (ranked second). ::: ::: Conclusion for all tasks, we found that the introduction of a wide range of features was crucial to success. Importantly, our choice of machine learning algorithms allowed us to be versatile in our feature design, and to introduce a large number of features without overfitting and without encountering computing-resource bottlenecks.
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paper_title: Extracting medication information from clinical text

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The Third i2b2 Workshop on Natural Language Processing Challenges for Clinical Records focused on the identification of medications, their dosages, modes (routes) of administration, frequencies, durations, and reasons for administration in discharge summaries. This challenge is referred to as the medication challenge. For the medication challenge, i2b2 released detailed annotation guidelines along with a set of annotated discharge summaries. Twenty teams representing 23 organizations and nine countries participated in the medication challenge. The teams produced rule-based, machine learning, and hybrid systems targeted to the task. Although rule-based systems dominated the top 10, the best performing system was a hybrid. Of all medication-related fields, durations and reasons were the most difficult for all systems to detect. While medications themselves were identified with better than 0.75 F-measure by all of the top 10 systems, the best F-measure for durations and reasons were 0.525 and 0.459, respectively. State-of-the-art natural language processing systems go a long way toward extracting medication names, dosages, modes, and frequencies. However, they are limited in recognizing duration and reason fields and would benefit from future research.
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paper_title: A shared task involving multi-label classification of clinical free text

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This paper reports on a shared task involving the assignment of ICD-9-CM codes to radiology reports. Two features distinguished this task from previous shared tasks in the biomedical domain. One is that it resulted in the first freely distributable corpus of fully anonymized clinical text. This resource is permanently available and will (we hope) facilitate future research. The other key feature of the task is that it required categorization with respect to a large and commercially significant set of labels. The number of participants was larger than in any previous biomedical challenge task. We describe the data production process and the evaluation measures, and give a preliminary analysis of the results. Many systems performed at levels approaching the inter-coder agreement, suggesting that human-like performance on this task is within the reach of currently available technologies.
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paper_title: Extracting information from textual documents in the electronic health record: a review of recent research.

paper_content:

Objectives: We examine recent published research on the extraction of information from textual documents in the Electronic Health Record (EHR). Methods: Literature review of the research published after 1995, based on PubMed, conference proceedings, and the ACM Digital Library, as well as on relevant publications referenced in papers already included. Results: 174 publications were selected and are discussed in this review in terms of methods used, pre-processing of textual documents, contextual features detection and analysis, extraction of information in general, extraction of codes and of information for decision-support and enrichment of the EHR, information extraction for surveillance, research, automated terminology management, and data mining, and de-identification of clinical text. Conclusions: Performance of information extraction systems with clinical text has improved since the last systematic review in 1995, but they are still rarely applied outside of the laboratory they have been developed in. Competitive challenges for information extraction from clinical text, along with the availability of annotated clinical text corpora, and further improvements in system performance are important factors to stimulate advances in this field and to increase the acceptance and usage of these systems in concrete clinical and biomedical research contexts. Cli
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paper_title: Overview of BioNLP’09 Shared Task on Event Extraction

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The paper presents the design and implementation of the BioNLP'09 Shared Task, and reports the final results with analysis. The shared task consists of three sub-tasks, each of which addresses bio-molecular event extraction at a different level of specificity. The data was developed based on the GENIA event corpus. The shared task was run over 12 weeks, drawing initial interest from 42 teams. Of these teams, 24 submitted final results. The evaluation results are encouraging, indicating that state-of-the-art performance is approaching a practically applicable level and revealing some remaining challenges.
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paper_title: Comparative analysis of five protein-protein interaction corpora

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BackgroundGrowing interest in the application of natural language processing methods to biomedical text has led to an increasing number of corpora and methods targeting protein-protein interaction (PPI) extraction. However, there is no general consensus regarding PPI annotation and consequently resources are largely incompatible and methods are difficult to evaluate.ResultsWe present the first comparative evaluation of the diverse PPI corpora, performing quantitative evaluation using two separate information extraction methods as well as detailed statistical and qualitative analyses of their properties. For the evaluation, we unify the corpus PPI annotations to a shared level of information, consisting of undirected, untyped binary interactions of non-static types with no identification of the words specifying the interaction, no negations, and no interaction certainty.We find that the F-score performance of a state-of-the-art PPI extraction method varies on average 19 percentage units and in some cases over 30 percentage units between the different evaluated corpora. The differences stemming from the choice of corpus can thus be substantially larger than differences between the performance of PPI extraction methods, which suggests definite limits on the ability to compare methods evaluated on different resources. We analyse a number of potential sources for these differences and identify factors explaining approximately half of the variance. We further suggest ways in which the difficulty of the PPI extraction tasks codified by different corpora can be determined to advance comparability. Our analysis also identifies points of agreement and disagreement in PPI corpus annotation that are rarely explicitly stated by the authors of the corpora.ConclusionsOur comparative analysis uncovers key similarities and differences between the diverse PPI corpora, thus taking an important step towards standardization. In the course of this study we have created a major practical contribution in converting the corpora into a shared format. The conversion software is freely available at http://mars.cs.utu.fi/PPICorpora.
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paper_title: Overcoming barriers to NLP for clinical text: the role of shared tasks and the need for additional creative solutions

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This issue of JAMIA focuses on natural language processing (NLP) techniques for clinical-text information extraction. Several articles are offshoots of the yearly ‘Informatics for Integrating Biology and the Bedside’ (i2b2) (http://www.i2b2.org) NLP shared-task challenge, introduced by Uzuner et al ( see page 552 )1 and co-sponsored by the Veteran's Administration for the last 2 years. This shared task follows long-running challenge evaluations in other fields, such as the Message Understanding Conference (MUC) for information extraction,2 TREC3 for text information retrieval, and CASP4 for protein structure prediction. Shared tasks in the clinical domain are recent and include annual i2b2 Challenges that began in 2006, a challenge for multi-label classification of radiology reports sponsored by Cincinnati Children's Hospital in 2007,5 a 2011 Cincinnati Children's Hospital challenge on suicide notes,6 and the 2011 TREC information retrieval shared task involving retrieval of clinical cases from narrative records.7 ::: ::: Although NLP research in the clinical domain has been active since the 1960s, progress in the development of NLP applications for clinical text has been slow and lags behind progress in the general NLP domain. There are several barriers to NLP development in the clinical domain, and shared tasks like the i2b2/VA Challenge address some of these barriers. Nevertheless, many barriers remain and unless the community takes a more active role in developing novel approaches for addressing the barriers, advancement and innovation will continue to be slow. ::: ::: Historically, there have been substantial barriers to NLP development in the clinical domain. These barriers are not unique to the clinical domain: they also occur in the fields of software engineering and general NLP. ::: ::: ### Lack of access to shared data ::: ::: Because of concerns regarding patient privacy and worry about revealing unfavorable institutional practices, hospitals and clinics have been extremely reluctant to allow access to clinical data for researchers from outside … ::: ::: Correspondence to Dr Wendy W Chapman, Department of Biomedical Informatics, University of California San Diego, 9500 Gilman Dr, Bldg 2 #0728, La Jolla, California, USA; wwchapman{at}ucsd.edu
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paper_title: Integrated Annotation For Biomedical Information Extraction

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We describe an approach to two areas of biomedical information extraction, drug development and cancer genomics. We have developed a framework which includes corpus annotation integrated at multiple levels: a Treebank containing syntactic structure, a Propbank containing predicate-argument structure, and annotation of entities and relations among the entities. Crucial to this approach is the proper characterization of entities as relation components, which allows the integration of the entity annotation with the syntactic structure while retaining the capacity to annotate and extract more complex events. We are training statistical taggers using this annotation for such extraction as well as using them for improving the annotation process.
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paper_title: Semantic annotation of biological concepts interplaying microbial cellular responses

paper_content:

BackgroundAutomated extraction systems have become a time saving necessity in Systems Biology. Considerable human effort is needed to model, analyse and simulate biological networks. Thus, one of the challenges posed to Biomedical Text Mining tools is that of learning to recognise a wide variety of biological concepts with different functional roles to assist in these processes.ResultsHere, we present a novel corpus concerning the integrated cellular responses to nutrient starvation in the model-organism Escherichia coli. Our corpus is a unique resource in that it annotates biomedical concepts that play a functional role in expression, regulation and metabolism. Namely, it includes annotations for genetic information carriers (genes and DNA, RNA molecules), proteins (transcription factors, enzymes and transporters), small metabolites, physiological states and laboratory techniques. The corpus consists of 130 full-text papers with a total of 59043 annotations for 3649 different biomedical concepts; the two dominant classes are genes (highest number of unique concepts) and compounds (most frequently annotated concepts), whereas other important cellular concepts such as proteins account for no more than 10% of the annotated concepts.ConclusionsTo the best of our knowledge, a corpus that details such a wide range of biological concepts has never been presented to the text mining community. The inter-annotator agreement statistics provide evidence of the importance of a consolidated background when dealing with such complex descriptions, the ambiguities naturally arising from the terminology and their impact for modelling purposes.Availability is granted for the full-text corpora of 130 freely accessible documents, the annotation scheme and the annotation guidelines. Also, we include a corpus of 340 abstracts.
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paper_title: Identifying patient smoking status from medical discharge records.

paper_content:

The authors organized a Natural Language Processing (NLP) challenge on automatically determining the smoking status of patients from information found in their discharge records. This challenge was issued as a part of the i2b2 (Informatics for Integrating Biology to the Bedside) project, to survey, facilitate, and examine studies in medical language understanding for clinical narratives. This article describes the smoking challenge, details the data and the annotation process, explains the evaluation metrics, discusses the characteristics of the systems developed for the challenge, presents an analysis of the results of received system runs, draws conclusions about the state of the art, and identifies directions for future research. A total of 11 teams participated in the smoking challenge. Each team submitted up to three system runs, providing a total of 23 submissions. The submitted system runs were evaluated with microaveraged and macroaveraged precision, recall, and F-measure. The systems submitted to the smoking challenge represented a variety of machine learning and rule-based algorithms. Despite the differences in their approaches to smoking status identification, many of these systems provided good results. There were 12 system runs with microaveraged F-measures above 0.84. Analysis of the results highlighted the fact that discharge summaries express smoking status using a limited number of textual features (e.g., "smok", "tobac", "cigar", Social History, etc.). Many of the effective smoking status identifiers benefit from these features.
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paper_title: The CLEF corpus: semantic annotation of clinical text.

paper_content:

The Clinical E-Science Framework (CLEF) project is building a framework for the capture, integration and presentation of clinical information: for clinical research, evidence-based health care and genotype-meets-phenotype informatics. A significant portion of the information required by such a framework originates as text, even in EHR-savvy organizations. CLEF uses Information Extraction (IE) to make this unstructured information available. An important part of IE is the identification of semantic entities and relationships. Typical approaches require human annotated documents to provide both evaluation standards and material for system development. CLEF has a corpus of clinical narratives, histopathology reports and imaging reports from 20 thousand patients. We describe the selection of a subset of this corpus for manual annotation of clinical entities and relationships. We describe an annotation methodology and report encouraging initial results of inter-annotator agreement. Comparisons are made between different text sub-genres, and between annotators with different skills.
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paper_title: Identifying Smokers with a Medical Extraction System

paper_content:

The Clinical Language Understanding group at Nuance Communications has developed a medical information extraction system that combines a rule-based extraction engine with machine learning algorithms to identify and categorize references to patient smoking in clinical reports. The extraction engine identifies smoking references; documents that contain no smoking references are classified as UNKNOWN. For the remaining documents, the extraction engine uses linguistic analysis to associate features such as status and time to smoking mentions. Machine learning is used to classify the documents based on these features. This approach shows overall accuracy in the 90s on all data sets used. Classification using engine-generated and word-based features outperforms classification using only word-based features for all data sets, although the difference gets smaller as the data set size increases. These techniques could be applied to identify other risk factors, such as drug and alcohol use, or a family history of a disease.
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paper_title: Chemical Names: Terminological Resources and Corpora Annotation

paper_content:

Chemical compounds like small signal molecules or other biological active chemical substances are an important entity class in life science publications and patents. The recognition of these named entities relies on appropriate dictionary resources as well as on training and evaluation corpora. In this work we give an overview of publicly available chemical information resources with respect to chemical terminology. The coverage, amount of synonyms, and especially the inclusion of SMILES or InChI are considered. Normalization of different chemical names to a unique structure is only possible with these structure representations. In addition, the generation and annotation of training and testing corpora is presented. We describe a small corpus for the evaluation of dictionaries containing chemical enities as well as a training and test corpus for the recognition of IUPAC and IUPAC-like names, which cannot be fully enumerated in dictionaries. Corpora can be found on http://www.scai.fraunhofer.de/chem-corpora.html
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paper_title: Annotation of Chemical Named Entities

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We describe the annotation of chemical named entities in scientific text. A set of annotation guidelines defines 5 types of named entities, and provides instructions for the resolution of special cases. A corpus of fulltext chemistry papers was annotated, with an inter-annotator agreement F score of 93%. An investigation of named entity recognition using LingPipe suggests that F scores of 63% are possible without customisation, and scores of 74% are possible with the addition of custom tokenisation and the use of dictionaries.
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paper_title: The Extraction of Pharmacogenetic and Pharmacogenomic Relations - A Case Study Using PharmGKB

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In this paper, we report on adapting the JREX relation extraction engine, originally developed For the elicitation of protein-protein interaction relations, to the domains of pharmacogenetics and pharmacogenomics. We propose an intrinsic and an extrinsic evaluation scenario which is based on knowledge contained in the PharmGKB knowledge base. Porting JREX yields favorable results in the range of 80% F-score for Gene-Disease, Gene-Drug, and Drug-Disease relations.
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paper_title: An Empirical Evaluation of Resources for the Identification of Diseases and Adverse Effects in Biomedical Literature

paper_content:

The mentions of human health perturbations such as the diseases and adverse effects denote a special entity class in the biomedical ::: literature. They help in understanding the underlying risk factors and develop a preventive rationale. The recognition of these named ::: entities in texts through dictionary-based approaches relies on the availability of appropriate terminological resources. Although few ::: resources are publicly available, not all are suitable for the text mining needs. Therefore, this work provides an overview of the well ::: known resources with respect to human diseases and adverse effects such as the MeSH, MedDRA, ICD-10, SNOMED CT, and UMLS. ::: Individual dictionaries are generated from these resources and their performance in recognizing the named entities is evaluated over a ::: manually annotated corpus. In addition, the steps for curating the dictionaries, rule-based acronym disambiguation and their impact ::: on the dictionary performance is discussed. The results show that the MedDRA and UMLS achieve the best recall. Besides this, ::: MedDRA provides an additional benefit of achieving a higher precision. The combination of search results of all the dictionaries achieve ::: a considerably high recall. The corpus is available on http://www.scai.fraunhofer.de/disease-ae-corpus.html
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paper_title: From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource

paper_content:

The mission of the Pharmacogenomics Knowledge Base (PharmGKB; www.pharmgkb.org) is to collect, encode and disseminate knowledge about the impact of human genetic variations on drug responses. It is an important worldwide resource of clinical pharmacogenomic biomarkers available to all. The PharmGKB website has evolved to highlight our knowledge curation and aggregation over our previous emphasis on collecting primary data. This review summarizes the methods we use to drive this expanded scope of ‘Knowledge Acquisition to Clinical Applications’, the new features available on our website and our future goals.
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paper_title: The 1st DDIExtraction-2011 challenge task: Extraction of Drug-Drug Interactions from biomedical texts Challenge Task on Drug-Drug Interaction Extraction

paper_content:

We present an evaluation task designed to provide a frame- work for comparing different approaches to extracting drug-drug interac- tions from biomedical texts. We define the task, describe the training/test data, list the participating systems and discuss their results. There were 10 teams who submitted a total of 40 runs.
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paper_title: Pharmacogenomics and bioinformatics: PharmGKB.

paper_content:

The NIH initiated the PharmGKB in April 2000. The primary mission was to create a repository of primary data, tools to track associations between genes and drugs, and to catalog the location and frequency of genetic variations known to impact drug response. Over the past 10 years, new technologies have shifted research from candidate gene pharmacogenetics to phenotype-based pharmacogenomics with a consequent explosion of data. PharmGKB has refocused on curating knowledge rather than housing primary genotype and phenotype data, and now, captures more complex relationships between genes, variants, drugs, diseases and pathways. Going forward, the challenges are to provide the tools and knowledge to plan and interpret genome-wide pharmacogenomics studies, predict gene-drug relationships based on shared mechanisms and support data-sharing consortia investigating clinical applications of pharmacogenomics.
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paper_title: A corpus of full-text journal articles is a robust evaluation tool for revealing differences in performance of biomedical natural language processing tools

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BackgroundWe introduce the linguistic annotation of a corpus of 97 full-text biomedical publications, known as the Colorado Richly Annotated Full Text (CRAFT) corpus. We further assess the performance of existing tools for performing sentence splitting, tokenization, syntactic parsing, and named entity recognition on this corpus.ResultsMany biomedical natural language processing systems demonstrated large differences between their previously published results and their performance on the CRAFT corpus when tested with the publicly available models or rule sets. Trainable systems differed widely with respect to their ability to build high-performing models based on this data.ConclusionsThe finding that some systems were able to train high-performing models based on this corpus is additional evidence, beyond high inter-annotator agreement, that the quality of the CRAFT corpus is high. The overall poor performance of various systems indicates that considerable work needs to be done to enable natural language processing systems to work well when the input is full-text journal articles. The CRAFT corpus provides a valuable resource to the biomedical natural language processing community for evaluation and training of new models for biomedical full text publications.
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paper_title: Normalized names for clinical drugs: RxNorm at 6 years.

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Objective In the 6 years since the National Library of Medicine began monthly releases of RxNorm, RxNorm has become a central resource for communicating about clinical drugs and supporting interoperation between drug vocabularies. ::: ::: Materials and methods Built on the idea of a normalized name for a medication at a given level of abstraction, RxNorm provides a set of names and relationships based on 11 different external source vocabularies. The standard model enables decision support to take place for a variety of uses at the appropriate level of abstraction. With the incorporation of National Drug File Reference Terminology (NDF-RT) from the Veterans Administration, even more sophisticated decision support has become possible. ::: ::: Discussion While related products such as RxTerms, RxNav, MyMedicationList, and MyRxPad have been recognized as helpful for various uses, tasks such as identifying exactly what is and is not on the market remain a challenge.
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paper_title: Chemical Entities of Biological Interest: an update

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Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary of molecular entities focused on ‘small’ chemical compounds. The molecular entities in question are either natural products or synthetic products used to intervene in the processes of living organisms. Genome-encoded macromolecules (nucleic acids, proteins and peptides derived from proteins by cleavage) are not as a rule included in ChEBI. In addition to molecular entities, ChEBI contains groups (parts of molecular entities) and classes of entities. ChEBI includes an ontological classification, whereby the relationships between molecular entities or classes of entities and their parents and/or children are specified. ChEBI is available online at http://www.ebi.ac.uk/chebi/. This article reports on new features in ChEBI since the last NAR report in 2007, including substructure and similarity searching, a submission tool for authoring of ChEBI datasets by the community and a 30-fold increase in the number of chemical structures stored in ChEBI.
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paper_title: The BioLexicon: a large-scale terminological resource for biomedical text mining

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BackgroundDue to the rapidly expanding body of biomedical literature, biologists require increasingly sophisticated and efficient systems to help them to search for relevant information. Such systems should account for the multiple written variants used to represent biomedical concepts, and allow the user to search for specific pieces of knowledge (or events) involving these concepts, e.g., protein-protein interactions. Such functionality requires access to detailed information about words used in the biomedical literature. Existing databases and ontologies often have a specific focus and are oriented towards human use. Consequently, biological knowledge is dispersed amongst many resources, which often do not attempt to account for the large and frequently changing set of variants that appear in the literature. Additionally, such resources typically do not provide information about how terms relate to each other in texts to describe events.ResultsThis article provides an overview of the design, construction and evaluation of a large-scale lexical and conceptual resource for the biomedical domain, the BioLexicon. The resource can be exploited by text mining tools at several levels, e.g., part-of-speech tagging, recognition of biomedical entities, and the extraction of events in which they are involved. As such, the BioLexicon must account for real usage of words in biomedical texts. In particular, the BioLexicon gathers together different types of terms from several existing data resources into a single, unified repository, and augments them with new term variants automatically extracted from biomedical literature. Extraction of events is facilitated through the inclusion of biologically pertinent verbs (around which events are typically organized) together with information about typical patterns of grammatical and semantic behaviour, which are acquired from domain-specific texts. In order to foster interoperability, the BioLexicon is modelled using the Lexical Markup Framework, an ISO standard.ConclusionsThe BioLexicon contains over 2.2 M lexical entries and over 1.8 M terminological variants, as well as over 3.3 M semantic relations, including over 2 M synonymy relations. Its exploitation can benefit both application developers and users. We demonstrate some such benefits by describing integration of the resource into a number of different tools, and evaluating improvements in performance that this can bring.
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paper_title: Mayo clinical Text Analysis and Knowledge Extraction System (cTAKES): architecture, component evaluation and applications

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We aim to build and evaluate an open-source natural language processing system for information extraction from electronic medical record clinical free-text. We describe and evaluate our system, the clinical Text Analysis and Knowledge Extraction System (cTAKES), released open-source at . The cTAKES builds on existing open-source technologies—the Unstructured Information Management Architecture framework and OpenNLP natural language processing toolkit. Its components, specifically trained for the clinical domain, create rich linguistic and semantic annotations. Performance of individual components: sentence boundary detector accuracy=0.949; tokenizer accuracy=0.949; part-of-speech tagger accuracy=0.936; shallow parser F-score=0.924; named entity recognizer and system-level evaluation F-score=0.715 for exact and 0.824 for overlapping spans, and accuracy for concept mapping, negation, and status attributes for exact and overlapping spans of 0.957, 0.943, 0.859, and 0.580, 0.939, and 0.839, respectively. Overall performance is discussed against five applications. The cTAKES annotations are the foundation for methods and modules for higher-level semantic processing of clinical free-text.
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paper_title: The Lexicon Builder Web service: Building Custom Lexicons from two hundred Biomedical Ontologies

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Domain specific biomedical lexicons are extensively used by researchers for natural language processing tasks. Currently these lexicons are created manually by expert curators and there is a pressing need for automated methods to compile such lexicons. The Lexicon Builder Web service addresses this need and reduces the investment of time and effort involved in lexicon maintenance. The service has three components: Inclusion – selects one or several ontologies (or its branches) and includes preferred names and synonym terms; Exclusion – filters terms based on the term’s Medline frequency, syntactic type, UMLS semantic type and match with stopwords; Output – aggregates information, handles compression and output formats. Evaluation demonstrates that the service has high accuracy and runtime performance. It is currently being evaluated for several use cases to establish its utility in biomedical information processing tasks. The Lexicon Builder promotes collaboration, sharing and standardization of lexicons amongst researchers by automating the creation, maintainence and cross referencing of custom lexicons.
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paper_title: U-Compare bio-event meta-service: compatible BioNLP event extraction services

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Background: Bio-molecular event extraction from literature is recognized as an important task of bio text mining and, as such, many relevant systems have been developed and made available during the last decade. While such systems provide useful services individually, there is a need for a meta-service to enable comparison and ensemble of such services, offering optimal solutions for various purposes. Results: We have integrated nine event extraction systems in the U-Compare framework, making them intercompatible and interoperable with other U-Compare components. The U-Compare event meta-service provides various meta-level features for comparison and ensemble of multiple event extraction systems. Experimental results show that the performance improvements achieved by the ensemble are significant. Conclusions: While individual event extraction systems themselves provide useful features for bio text mining, the U-Compare meta-service is expected to improve the accessibility to the individual systems, and to enable metalevel uses over multiple event extraction systems such as comparison and ensemble.
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paper_title: Building a biomedical ontology recommender web service

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BackgroundResearchers in biomedical informatics use ontologies and terminologies to annotate their data in order to facilitate data integration and translational discoveries. As the use of ontologies for annotation of biomedical datasets has risen, a common challenge is to identify ontologies that are best suited to annotating specific datasets. The number and variety of biomedical ontologies is large, and it is cumbersome for a researcher to figure out which ontology to use.MethodsWe present the Biomedical Ontology Recommender web service. The system uses textual metadata or a set of keywords describing a domain of interest and suggests appropriate ontologies for annotating or representing the data. The service makes a decision based on three criteria. The first one is coverage, or the ontologies that provide most terms covering the input text. The second is connectivity, or the ontologies that are most often mapped to by other ontologies. The final criterion is size, or the number of concepts in the ontologies. The service scores the ontologies as a function of scores of the annotations created using the National Center for Biomedical Ontology (NCBO) Annotator web service. We used all the ontologies from the UMLS Metathesaurus and the NCBO BioPortal.ResultsWe compare and contrast our Recommender by an exhaustive functional comparison to previously published efforts. We evaluate and discuss the results of several recommendation heuristics in the context of three real world use cases. The best recommendations heuristics, rated ‘very relevant’ by expert evaluators, are the ones based on coverage and connectivity criteria. The Recommender service (alpha version) is available to the community and is embedded into BioPortal.
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paper_title: U-Compare: share and compare text mining tools with UIMA

paper_content:

Summary: Due to the increasing number of text mining resources (tools and corpora) available to biologists, interoperability issues between these resources are becoming significant obstacles to using them effectively. UIMA, the Unstructured Information Management Architecture, is an open framework designed to aid in the construction of more interoperable tools. U-Compare is built on top of the UIMA framework, and provides both a concrete framework for out-of-the-box text mining and a sophisticated evaluation platform allowing users to run specific tools on any target text, generating both detailed statistics and instance-based visualizations of outputs. U-Compare is a joint project, providing the world's largest, and still growing, collection of UIMA-compatible resources. These resources, originally developed by different groups for a variety of domains, include many famous tools and corpora. U-Compare can be launched straight from the web, without needing to be manually installed. All U-Compare components are provided ready-to-use and can be combined easily via a drag-and-drop interface without any programming. External UIMA components can also simply be mixed with U-Compare components, without distinguishing between locally and remotely deployed resources. ::: ::: Availability: http://u-compare.org/ ::: ::: Contact: kano@is.s.u-tokyo.ac.jp
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paper_title: UIMA: an architectural approach to unstructured information processing in the corporate research environment

paper_content:

IBM Research has over 200 people working on Unstructured Information Management (UIM) technologies with a strong focus on Natural Language Processing (NLP). These researchers are engaged in activities ranging from natural language dialog, information retrieval, topic-tracking, named-entity detection, document classification and machine translation to bioinformatics and open-domain question answering. An analysis of these activities strongly suggested that improving the organization's ability to quickly discover each other's results and rapidly combine different technologies and approaches would accelerate scientific advance. Furthermore, the ability to reuse and combine results through a common architecture and a robust software framework would accelerate the transfer of research results in NLP into IBM's product platforms. Market analyses indicating a growing need to process unstructured information, specifically multilingual, natural language text, coupled with IBM Research's investment in NLP, led to the development of middleware architecture for processing unstructured information dubbed UIMA. At the heart of UIMA are powerful search capabilities and a data-driven framework for the development, composition and distributed deployment of analysis engines. In this paper we give a general introduction to UIMA focusing on the design points of its analysis engine architecture and we discuss how UIMA is helping to accelerate research and technology transfer.
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paper_title: Linked open drug data for pharmaceutical research and development

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There is an abundance of information about drugs available on the Web. Data sources range from medicinal chemistry results, over the impact of drugs on gene expression, to the outcomes of drugs in clinical trials. These data are typically not connected together, which reduces the ease with which insights can be gained. Linking Open Drug Data (LODD) is a task force within the World Wide Web Consortium's (W3C) Health Care and Life Sciences Interest Group (HCLS IG). LODD has surveyed publicly available data about drugs, created Linked Data representations of the data sets, and identified interesting scientific and business questions that can be answered once the data sets are connected. The task force provides recommendations for the best practices of exposing data in a Linked Data representation. In this paper, we present past and ongoing work of LODD and discuss the growing importance of Linked Data as a foundation for pharmaceutical R&D data sharing.
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paper_title: Ontology-Based Knowledge Discovery in Pharmacogenomics

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One current challenge in biomedicine is to analyze large amounts of complex biological data for extracting domain knowledge. This work holds on the use of knowledge-based techniques such as knowledge discovery (KD) and knowledge representation (KR) in pharmacogenomics, where knowledge units represent genotype–phenotype relationships in the context of a given treatment. An objective is to design knowledge base (KB, here also mentioned as an ontology) and then to use it in the KD process itself. A method is proposed for dealing with two main tasks: (1) building a KB from heterogeneous data related to genotype, phenotype, and treatment, and (2) applying KD techniques on knowledge assertions for extracting genotype–phenotype relationships. An application was carried out on a clinical trial concerned with the variability of drug response to montelukast treatment. Genotype–genotype and genotype–phenotype associations were retrieved together with new associations, allowing the extension of the initial KB. This experiment shows the potential of KR and KD processes, especially for designing KB, checking KB consistency, and reasoning for problem solving.
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paper_title: An open annotation ontology for science on web 3.0

paper_content:

BackgroundThere is currently a gap between the rich and expressive collection of published biomedical ontologies, and the natural language expression of biomedical papers consumed on a daily basis by scientific researchers. The purpose of this paper is to provide an open, shareable structure for dynamic integration of biomedical domain ontologies with the scientific document, in the form of an Annotation Ontology (AO), thus closing this gap and enabling application of formal biomedical ontologies directly to the literature as it emerges.MethodsInitial requirements for AO were elicited by analysis of integration needs between biomedical web communities, and of needs for representing and integrating results of biomedical text mining. Analysis of strengths and weaknesses of previous efforts in this area was also performed. A series of increasingly refined annotation tools were then developed along with a metadata model in OWL, and deployed for feedback and additional requirements the ontology to users at a major pharmaceutical company and a major academic center. Further requirements and critiques of the model were also elicited through discussions with many colleagues and incorporated into the work.ResultsThis paper presents Annotation Ontology (AO), an open ontology in OWL-DL for annotating scientific documents on the web. AO supports both human and algorithmic content annotation. It enables “stand-off” or independent metadata anchored to specific positions in a web document by any one of several methods. In AO, the document may be annotated but is not required to be under update control of the annotator. AO contains a provenance model to support versioning, and a set model for specifying groups and containers of annotation. AO is freely available under open source license at http://purl.org/ao/, and extensive documentation including screencasts is available on AO’s Google Code page: http://code.google.com/p/annotation-ontology/ .ConclusionsThe Annotation Ontology meets critical requirements for an open, freely shareable model in OWL, of annotation metadata created against scientific documents on the Web. We believe AO can become a very useful common model for annotation metadata on Web documents, and will enable biomedical domain ontologies to be used quite widely to annotate the scientific literature. Potential collaborators and those with new relevant use cases are invited to contact the authors.
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paper_title: Multi-way association extraction and visualization from biological text documents using hyper-graphs: Applications to genetic association studies for diseases

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Objectives: Biological research literature, as in many other domains of human endeavor, represents a rich, ever growing source of knowledge. An important form of such biological knowledge constitutes associations among biological entities such as genes, proteins, diseases, drugs and chemicals, etc. There has been a considerable amount of recent research in extraction of various kinds of binary associations (e.g., gene-gene, gene-protein, protein-protein, etc.) using different text mining approaches. However, an important aspect of such associations (e.g., ''gene A activates protein B'') is identifying the context in which such associations occur (e.g., ''gene A activates protein B in the context of disease C in organ D under the influence of chemical E''). Such contexts can be represented appropriately by a multi-way relationship involving more than two objects (e.g., objects A, B, C, D, E) rather than usual binary relationship (objects A and B). Methods: Such multi-way relations naturally lead to a hyper-graph representation of the knowledge rather than a binary graph. The hyper-graph based multi-way knowledge extraction from biological text literature represents a computationally difficult problem (due to its combinatorial nature) which has not received much attention from the Bioinformatics research community. In this paper, we describe and compare two different approaches to such multi-way hyper-graph extraction: one based on an exhaustive enumeration of all multi-way hyper-edges and the other based on an extension of the well-known A Priori algorithm for structured data to the case unstructured textual data. We also present a representative graph based approach towards visualizing these genetic association hyper-graphs. Results: Two case studies are conducted for two biomedical problems (related to the diseases of lung cancer and colorectal cancer respectively), illustrating that the latter approach (using the text-based A Priori method) identifies the same hyper-edges as the former approach (the exhaustive method), but at a much less computational cost. The extracted hyper-relations are presented in the paper as cognition-rich representative graphs, representing the corresponding hyper-graphs. Conclusions: The text-based A Priori algorithm is a practical, useful method to extract hyper-graphs representing multi-way associations among biological objects. These hyper-graphs and their visualization using representative graphs can provide important contextual information for understanding gene-gene associations relevant to specific diseases.
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paper_title: Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data

paper_content:

BackgroundRecently there has been an explosion of new data sources about genes, proteins, genetic variations, chemical compounds, diseases and drugs. Integration of these data sources and the identification of patterns that go across them is of critical interest. Initiatives such as Bio2RDF and LODD have tackled the problem of linking biological data and drug data respectively using RDF. Thus far, the inclusion of chemogenomic and systems chemical biology information that crosses the domains of chemistry and biology has been very limitedResultsWe have created a single repository called Chem2Bio2RDF by aggregating data from multiple chemogenomics repositories that is cross-linked into Bio2RDF and LODD. We have also created a linked-path generation tool to facilitate SPARQL query generation, and have created extended SPARQL functions to address specific chemical/biological search needs. We demonstrate the utility of Chem2Bio2RDF in investigating polypharmacology, identification of potential multiple pathway inhibitors, and the association of pathways with adverse drug reactions.ConclusionsWe have created a new semantic systems chemical biology resource, and have demonstrated its potential usefulness in specific examples of polypharmacology, multiple pathway inhibition and adverse drug reaction - pathway mapping. We have also demonstrated the usefulness of extending SPARQL with cheminformatics and bioinformatics functionality.
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paper_title: Consistent visualizations of changing knowledge

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Networks are increasingly used in biology to represent complex data in uncomplicated symbolic form. However, as biological knowledge is continually evolving, so must those networks representing this knowledge. Capturing and presenting this type of knowledge change over time is particularly challenging due to the intimate manner in which researchers customize those networks they come into contact with. The effective visualization of this knowledge is important as it creates insight into complex systems and stimulates hypothesis generation and biological discovery. Here we highlight how the retention of user customizations, and the collection and visualization of knowledge associated provenance supports effective and productive network exploration. We also present an extension of the Hanalyzer system, ReOrient, which supports network exploration and analysis in the presence of knowledge change.
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paper_title: The anatomy of a nanopublication

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As the amount of scholarly communication increases, it is increasingly difficult for specific core scientific statements to be found, connected and curated. Additionally, the redundancy of these statements in multiple fora makes it difficult to determine attribution, quality and provenance. To tackle these challenges, the Concept Web Alliance has promoted the notion of nanopublications (core scientific statements with associated context). In this document, we present a model of nanopublications along with a Named Graph/RDF serialization of the model. Importantly, the serialization is defined completely using already existing community-developed technologies. Finally, we discuss the importance of aggregating nanopublications and the role that the Concept Wiki plays in facilitating it.
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paper_title: Biomedical Discovery Acceleration, with Applications to Craniofacial Development

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The profusion of high-throughput instruments and the explosion of new results in the scientific literature, particularly in molecular biomedicine, is both a blessing and a curse to the bench researcher. Even knowledgeable and experienced scientists can benefit from computational tools that help navigate this vast and rapidly evolving terrain. In this paper, we describe a novel computational approach to this challenge, a knowledge-based system that combines reading, reasoning, and reporting methods to facilitate analysis of experimental data. Reading methods extract information from external resources, either by parsing structured data or using biomedical language processing to extract information from unstructured data, and track knowledge provenance. Reasoning methods enrich the knowledge that results from reading by, for example, noting two genes that are annotated to the same ontology term or database entry. Reasoning is also used to combine all sources into a knowledge network that represents the integration of all sorts of relationships between a pair of genes, and to calculate a combined reliability score. Reporting methods combine the knowledge network with a congruent network constructed from experimental data and visualize the combined network in a tool that facilitates the knowledge-based analysis of that data. An implementation of this approach, called the Hanalyzer, is demonstrated on a large-scale gene expression array dataset relevant to craniofacial development. The use of the tool was critical in the creation of hypotheses regarding the roles of four genes never previously characterized as involved in craniofacial development; each of these hypotheses was validated by further experimental work.
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paper_title: Towards pharmacogenomics knowledge discovery with the semantic web

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Pharmacogenomics aims to understand pharmacological response with respect to genetic variation. Essential to the delivery of better health care is the use of pharmacogenomics knowledge to answer questions about therapeutic, pharmacological or genetic aspects. Several XML markup languages have been developed to capture pharmacogenomic and related information so as to facilitate data sharing. However, recent advances in semantic web technologies have presented exciting new opportunities for pharmacogenomics knowledge discovery by representing the information with machine understandable semantics. Progress in this area is illustrated with reference to the personalized medicine project that aims to facilitate pharmacogenomics knowledge discovery through intuitive knowledge capture and sophisticated question answering using automated reasoning over expressive ontologies.
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paper_title: Integration and publication of heterogeneous text-mined relationships on the Semantic Web

paper_content:

BackgroundAdvances in Natural Language Processing (NLP) techniques enable the extraction of fine-grained relationships mentioned in biomedical text. The variability and the complexity of natural language in expressing similar relationships causes the extracted relationships to be highly heterogeneous, which makes the construction of knowledge bases difficult and poses a challenge in using these for data mining or question answering.ResultsWe report on the semi-automatic construction of the PHARE relationship ontology (the PHArmacogenomic RElationships Ontology) consisting of 200 curated relations from over 40,000 heterogeneous relationships extracted via text-mining. These heterogeneous relations are then mapped to the PHARE ontology using synonyms, entity descriptions and hierarchies of entities and roles. Once mapped, relationships can be normalized and compared using the structure of the ontology to identify relationships that have similar semantics but different syntax. We compare and contrast the manual procedure with a fully automated approach using WordNet to quantify the degree of integration enabled by iterative curation and refinement of the PHARE ontology. The result of such integration is a repository of normalized biomedical relationships, named PHARE-KB, which can be queried using Semantic Web technologies such as SPARQL and can be visualized in the form of a biological network.ConclusionsThe PHARE ontology serves as a common semantic framework to integrate more than 40,000 relationships pertinent to pharmacogenomics. The PHARE ontology forms the foundation of a knowledge base named PHARE-KB. Once populated with relationships, PHARE-KB (i) can be visualized in the form of a biological network to guide human tasks such as database curation and (ii) can be queried programmatically to guide bioinformatics applications such as the prediction of molecular interactions. PHARE is available at http://purl.bioontology.org/ontology/PHARE.
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paper_title: The Open Biomedical Annotator

paper_content:

The range of publicly available biomedical data is enormous and is expanding fast. This expansion means that researchers now face a hurdle to extracting the data they need from the large numbers of data that are available. Biomedical researchers have turned to ontologies and terminologies to structure and annotate their data with ontology concepts for better search and retrieval. However, this annotation process cannot be easily automated and often requires expert curators. Plus, there is a lack of easy-to-use systems that facilitate the use of ontologies for annotation. This paper presents the Open Biomedical Annotator (OBA), an ontology-based Web service that annotates public datasets with biomedical ontology concepts based on their textual metadata (www.bioontology.org). The biomedical community can use the annotator service to tag datasets automatically with ontology terms (from UMLS and NCBO BioPortal ontologies). Such annotations facilitate translational discoveries by integrating annotated data.[1]
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paper_title: Drug repurposing and adverse event prediction using high-throughput literature analysis.

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Drug repurposing is the process of using existing drugs in indications other than the ones they were originally designed for. It is an area of significant recent activity due to the mounting costs of traditional drug development and scarcity of new chemical entities brought to the market by bio-pharmaceutical companies. By selecting drugs that already satisfy basic toxicity, ADME and related criteria, drug repurposing promises to deliver significant value at reduced cost and in dramatically shorter time frames than is normally the case for the drug development process. The same process that results in drug repurposing can also be used for the prediction of adverse events of known or novel drugs. The analytics method is based on the description of the mechanism of action of a drug, which is then compared to the molecular mechanisms underlying all known adverse events. This review will focus on those approaches to drug repurposing and adverse event prediction that are based on the biomedical literature. Such approaches typically begin with an analysis of the literature and aim to reveal indirect relationships among seemingly unconnected biomedical entities such as genes, signaling pathways, physiological processes, and diseases. Networks of associations of these entities allow the uncovering of the molecular mechanisms underlying a disease, better understanding of the biological effects of a drug and the evaluation of its benefit/risk profile. In silico results can be tested in relevant cellular and animal models and, eventually, in clinical trials.
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paper_title: BioCreative III interactive task: an overview

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BackgroundThe BioCreative challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems applied to the biological domain. The biocurator community, as an active user of biomedical literature, provides a diverse and engaged end user group for text mining tools. Earlier BioCreative challenges involved many text mining teams in developing basic capabilities relevant to biological curation, but they did not address the issues of system usage, insertion into the workflow and adoption by curators. Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to address the utility and usability of text mining tools for real-life biocuration tasks. To support the aims of the IAT in BC-III, involvement of both developers and end users was solicited, and the development of a user interface to address the tasks interactively was requested.ResultsA User Advisory Group (UAG) actively participated in the IAT design and assessment. The task focused on gene normalization (identifying gene mentions in the article and linking these genes to standard database identifiers), gene ranking based on the overall importance of each gene mentioned in the article, and gene-oriented document retrieval (identifying full text papers relevant to a selected gene). Six systems participated and all processed and displayed the same set of articles. The articles were selected based on content known to be problematic for curation, such as ambiguity of gene names, coverage of multiple genes and species, or introduction of a new gene name. Members of the UAG curated three articles for training and assessment purposes, and each member was assigned a system to review. A questionnaire related to the interface usability and task performance (as measured by precision and recall) was answered after systems were used to curate articles. Although the limited number of articles analyzed and users involved in the IAT experiment precluded rigorous quantitative analysis of the results, a qualitative analysis provided valuable insight into some of the problems encountered by users when using the systems. The overall assessment indicates that the system usability features appealed to most users, but the system performance was suboptimal (mainly due to low accuracy in gene normalization). Some of the issues included failure of species identification and gene name ambiguity in the gene normalization task leading to an extensive list of gene identifiers to review, which, in some cases, did not contain the relevant genes. The document retrieval suffered from the same shortfalls. The UAG favored achieving high performance (measured by precision and recall), but strongly recommended the addition of features that facilitate the identification of correct gene and its identifier, such as contextual information to assist in disambiguation.DiscussionThe IAT was an informative exercise that advanced the dialog between curators and developers and increased the appreciation of challenges faced by each group. A major conclusion was that the intended users should be actively involved in every phase of software development, and this will be strongly encouraged in future tasks. The IAT Task provides the first steps toward the definition of metrics and functional requirements that are necessary for designing a formal evaluation of interactive curation systems in the BioCreative IV challenge.
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paper_title: Discovery and Explanation of Drug-Drug Interactions via Text Mining

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Drug-drug interactions (DDIs) can occur when two drugs interact with the same gene product. Most available information about gene-drug relationships is contained within the scientific literature, but is dispersed over a large number of publications, with thousands of new publications added each month. In this setting, automated text mining is an attractive solution for identifying gene-drug relationships and aggregating them to predict novel DDIs. In previous work, we have shown that gene-drug interactions can be extracted from Medline abstracts with high fidelity - we extract not only the genes and drugs, but also the type of relationship expressed in individual sentences (e.g. metabolize, inhibit, activate and many others). We normalize these relationships and map them to a standardized ontology. In this work, we hypothesize that we can combine these normalized gene-drug relationships, drawn from a very broad and diverse literature, to infer DDIs. Using a training set of established DDIs, we have trained a random forest classifier to score potential DDIs based on the features of the normalized assertions extracted from the literature that relate two drugs to a gene product. The classifier recognizes the combinations of relationships, drugs and genes that are most associated with the gold standard DDIs, correctly identifying 79.8% of assertions relating interacting drug pairs and 78.9% of assertions relating noninteracting drug pairs. Most significantly, because our text processing method captures the semantics of individual gene-drug relationships, we can construct mechanistic pharmacological explanations for the newly-proposed DDIs. We show how our classifier can be used to explain known DDIs and to uncover new DDIs that have not yet been reported.
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paper_title: Ontology-Based Knowledge Discovery in Pharmacogenomics

paper_content:

One current challenge in biomedicine is to analyze large amounts of complex biological data for extracting domain knowledge. This work holds on the use of knowledge-based techniques such as knowledge discovery (KD) and knowledge representation (KR) in pharmacogenomics, where knowledge units represent genotype–phenotype relationships in the context of a given treatment. An objective is to design knowledge base (KB, here also mentioned as an ontology) and then to use it in the KD process itself. A method is proposed for dealing with two main tasks: (1) building a KB from heterogeneous data related to genotype, phenotype, and treatment, and (2) applying KD techniques on knowledge assertions for extracting genotype–phenotype relationships. An application was carried out on a clinical trial concerned with the variability of drug response to montelukast treatment. Genotype–genotype and genotype–phenotype associations were retrieved together with new associations, allowing the extension of the initial KB. This experiment shows the potential of KR and KD processes, especially for designing KB, checking KB consistency, and reasoning for problem solving.
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paper_title: Literature mining in support of drug discovery

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The drug discovery enterprise provides strong drivers for data integration. While attention in this arena has tended to focus on integration of primary data from omics and other large platform technologies contributing to drug discovery and development, the scientific literature remains a major source of information valuable to pharmaceutical enterprises, and therefore tools for mining such data and integrating it with other sources are of vital interest and economic impact. This review provides a brief overview of approaches to literature mining as they relate to drug discovery, and offers an illustrative case study of a 'lightweight' approach we have implemented within an industrial context.
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paper_title: Mining gene-disease relationships from biomedical literature: weighting protein-protein interactions and connectivity measures.

paper_content:

Motivation: The promises of the post-genome era disease-related discoveries and advances have yet to be fully realized, with many opportunities for discovery hiding in the millions of biomedical papers published since. Public databases give access to data extracted from the literature by teams of experts, but their coverage is often limited and lags behind recent discoveries. We present a computational method that combines data extracted from the literature with data from curated sources in order to uncover possible gene-disease relationships that are not directly stated or were missed by the initial mining. Method: An initial set of genes and proteins is obtained from gene-disease relationships extracted from PubMed abstracts using natural language processing. Interactions involving the corresponding proteins are similarly extracted and integrated with interactions from curated databases (such as BIND and DIP), assigning a confidence measure to each interaction depending on its source. The augmented list of genes and gene products is then ranked combining two scores: one that reflects the strength of the relationship with the initial set of genes and incorporates user-defined weights and another that reflects the importance of the gene in maintaining the connectivity of the network. We applied the method to atherosclerosis to assess its effectiveness. Results: Top-ranked proteins from the method are related to atherosclerosis with accuracy between 0.85 to 1.00 for the top 20 and 0.64 to 0.80 for the top 90 if duplicates are ignored, with 45% of the top 20 and 75% of the top 90 derived by the method, not extracted from text. Thus, though the initial gene set and interactions were automatically extracted from text (and subject to the impreciseness of automatic extraction), their use for further hypothesis generation is valuable given adequate computational analysis.
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paper_title: Ranking Interactions for a Curation Task

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One of the key pieces of information which biomedical text mining systems are expected to extract from the literature are interactions among different types of biomedical entities (proteins, genes, diseases, drugs, etc.). Different types of entities might be considered, for example protein-protein interactions have been extensively studied as part of the Bio Creative competitive evaluations. However, more complex interactions such as those among genes, drugs, and diseases are increasingly of interest. Different databases have been used as reference for the evaluation of extraction and ranking techniques. The aim of this paper is to describe a machine-learning based reranking approach for candidate interactions extracted from the literature. The results are evaluated using data derived from the Pharm GKB database. The importance of a good ranking is particularly evident when the results are applied to support human curators.
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paper_title: Computational polypharmacology with text mining and ontologies.

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Huge volumes of data, produced by microarrays and next- generation sequencing, are now at the fingertips of scientists and allow to expand the scope beyond conventional drug de- sign. New promiscuous drugs directed at multiple targets promise increased therapeutic efficacy for treatment of multi- factorial diseases. At the same time, more systematic tests for unwanted side effects are now possible. In this paper, we focus on the application of text mining and ontologies to support experimental drug discovery. Text mining is a high- throughput technique to extract information from millions of scientific documents and web pages. By exploiting the vast number of extracted facts as well as the indirect links between them, text mining and ontologies help to generate new hypotheses on drug target interactions. We review latest applications of text mining and ontologies suitable for target and drug-target interaction discovery in addition to conventional approaches. We conclude that mining the literature on drugs and proteins offers unique opportunities to support the laborious and expensive process of drug development.
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paper_title: Literature mining, ontologies and information visualization for drug repurposing.

paper_content:

The immense growth of MEDLINE coupled with the realization that a vast amount of biomedical knowledge is recorded in free-text format, has led to the appearance of a large number of literature mining techniques aiming to extract biomedical terms and their inter-relations from the scientific literature. Ontologies have been extensively utilized in the biomedical domain either as controlled vocabularies or to provide the framework for mapping relations between concepts in biology and medicine. Literature-based approaches and ontologies have been used in the past for the purpose of hypothesis generation in connection with drug discovery. Here, we review the application of literature mining and ontology modeling and traversal to the area of drug repurposing (DR). In recent years, DR has emerged as a noteworthy alternative to the traditional drug development process, in response to the decreased productivity of the biopharmaceutical industry. Thus, systematic approaches to DR have been developed, involving a variety of in silico, genomic and high-throughput screening technologies. Attempts to integrate literature mining with other types of data arising from the use of these technologies as well as visualization tools assisting in the discovery of novel associations between existing drugs and new indications will also be presented.
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paper_title: Facts from text: can text mining help to scale-up high-quality manual curation of gene products with ontologies?

paper_content:

The biomedical literature can be seen as a large integrated, but unstructured data repository. Extracting facts from literature and making them accessible is approached from two directions: manual curation efforts develop ontologies and vocabularies to annotate gene products based on statements in papers. Text mining aims to automatically identify entities and their relationships in text using information retrieval and natural language processing techniques. Manual curation is highly accurate but time consuming, and does not scale with the ever increasing growth of literature. Text mining as a high-throughput computational technique scales well, but is error-prone due to the complexity of natural language. How can both be married to combine scalability and accuracy? Here, we review the state-of-the-art text mining approaches that are relevant to annotation and discuss available online services analysing biomedical literature by means of text mining techniques, which could also be utilised by annotation projects. We then examine how far text mining has already been utilised in existing annotation projects and conclude how these techniques could be tightly integrated into the manual annotation process through novel authoring systems to scale-up high-quality manual curation.
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paper_title: Text mining and manual curation of chemical-gene-disease networks for the Comparative Toxicogenomics Database (CTD)

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BackgroundThe Comparative Toxicogenomics Database (CTD) is a publicly available resource that promotes understanding about the etiology of environmental diseases. It provides manually curated chemical-gene/protein interactions and chemical- and gene-disease relationships from the peer-reviewed, published literature. The goals of the research reported here were to establish a baseline analysis of current CTD curation, develop a text-mining prototype from readily available open source components, and evaluate its potential value in augmenting curation efficiency and increasing data coverage.ResultsPrototype text-mining applications were developed and evaluated using a CTD data set consisting of manually curated molecular interactions and relationships from 1,600 documents. Preliminary results indicated that the prototype found 80% of the gene, chemical, and disease terms appearing in curated interactions. These terms were used to re-rank documents for curation, resulting in increases in mean average precision (63% for the baseline vs. 73% for a rule-based re-ranking), and in the correlation coefficient of rank vs. number of curatable interactions per document (baseline 0.14 vs. 0.38 for the rule-based re-ranking).ConclusionThis text-mining project is unique in its integration of existing tools into a single workflow with direct application to CTD. We performed a baseline assessment of the inter-curator consistency and coverage in CTD, which allowed us to measure the potential of these integrated tools to improve prioritization of journal articles for manual curation. Our study presents a feasible and cost-effective approach for developing a text mining solution to enhance manual curation throughput and efficiency.
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paper_title: Discovering drug–drug interactions: a text-mining and reasoning approach based on properties of drug metabolism

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Motivation: Identifying drug–drug interactions (DDIs) is a critical process in drug administration and drug development. Clinical support tools often provide comprehensive lists of DDIs, but they usually lack the supporting scientific evidences and different tools can return inconsistent results. In this article, we propose a novel approach that integrates text mining and automated reasoning to derive DDIs. Through the extraction of various facts of drug metabolism, not only the DDIs that are explicitly mentioned in text can be extracted but also the potential interactions that can be inferred by reasoning. ::: ::: Results: Our approach was able to find several potential DDIs that are not present in DrugBank. We manually evaluated these interactions based on their supporting evidences, and our analysis revealed that 81.3% of these interactions are determined to be correct. This suggests that our approach can uncover potential DDIs with scientific evidences explaining the mechanism of the interactions. ::: ::: Contact: luis.tari@roche.com
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paper_title: Integrating text mining into the MGI biocuration workflow

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A major challenge for functional and comparative genomics resource development is the extraction of data from the biomedical literature. Although text mining for biological data is an active research field, few applications have been integrated into production literature curation systems such as those of the model organism databases (MODs). Not only are most available biological natural language (bioNLP) and information retrieval and extraction solutions difficult to adapt to existing MOD curation workflows, but many also have high error rates or are unable to process documents available in those formats preferred by scientific journals. In September 2008, Mouse Genome Informatics (MGI) at The Jackson Laboratory initiated a search for dictionary-based text mining tools that we could integrate into our biocuration workflow. MGI has rigorous document triage and annotation procedures designed to identify appropriate articles about mouse genetics and genome biology. We currently screen � 1000 journal articles a month for Gene Ontology terms, gene mapping, gene expression, phenotype data and other key biological information. Although we do not foresee that curation tasks will ever be fully automated, we are eager to implement named entity recognition (NER) tools for gene tagging that can help streamline our curation workflow and simplify gene indexing tasks within the MGI system. Gene indexing is an MGI-specific curation function that involves identifying which mouse genes are being studied in an article, then associating the appropriate gene symbols with the article reference number in the MGI database. Here, we discuss our search process, performance metrics and success criteria, and how we identified a short list of potential text mining tools for further evaluation. We provide an overview of our pilot projects with NCBO’s Open Biomedical Annotator and Fraunhofer SCAI’s ProMiner. In doing so, we prove the potential for the further incorporation of semi-automated processes into the curation of the biomedical literature.
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paper_title: It’s about This and That: A Description of Anaphoric Expressions in Clinical Text

paper_content:

Although anaphoric expressions are very common in biomedical and clinical documents, little work has been done to systematically characterize their use in clinical text. Samples of ‘it’, ‘this’, and ‘that’ expressions occurring in inpatient clinical notes from four metropolitan hospitals were analyzed using a combination of semi-automated and manual annotation techniques. We developed a rule-based approach to filter potential non-referential expressions. A physician then manually annotated 1000 potential referential instances to determine referent status and the antecedent of each referent expression. A distributional analysis of the three referring expressions in the entire corpus of notes demonstrates a high prevalence of anaphora and large variance in distributions of referential expressions with different notes. Our results confirm that anaphoric expressions are common in clinical texts. Effective co-reference resolution with anaphoric expressions remains an important challenge in medical natural language processing research.
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paper_title: A Reappraisal of Sentence and Token Splitting for Life Sciences Documents

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Natural language processing of real-world documents requires several low-level tasks such as splitting a piece of text into its constituent sentences, and splitting each sentence into its constituent tokens to be performed by some preprocessor (prior to linguistic analysis). While this task is often considered as unsophisticated clerical work, in the life sciences domain it poses enormous problems due to complex naming conventions. In this paper, we first introduce an annotation framework for sentence and token splitting underlying a newly constructed sentence- and token-tagged biomedical text corpus. This corpus serves as a training environment and test bed for machine-learning based sentence and token splitters using Conditional Random Fields (CRFs). Our evaluation experiments reveal that CRFs with a rich feature set substantially increase sentence and token detection performance.
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paper_title: Zone analysis in biology articles as a basis for information extraction

paper_content:

Summary In the field of biomedicine, an overwhelming amount of experimental data has become available as a result of the high throughput of research in this domain. The amount of results reported has now grown beyond the limits of what can be managed by manual means. This makes it increasingly difficult for the researchers in this area to keep up with the latest developments. Information extraction (IE) in the biological domain aims to provide an effective automatic means to dynamically manage the information contained in archived journal articles and abstract collections and thus help researchers in their work. However, while considerable advances have been made in certain areas of IE, pinpointing and organizing factual information (such as experimental results) remains a challenge. In this paper we propose tackling this task by incorporating into IE information about rhetorical zones, i.e. classification of spans of text in terms of argumentation and intellectual attribution. As the first step towards this goal, we introduce a scheme for annotating biological texts for rhetorical zones and provide a qualitative and quantitative analysis of the data annotated according to this scheme. We also discuss our preliminary research on automatic zone analysis, and its incorporation into our IE framework.
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paper_title: Mayo clinical Text Analysis and Knowledge Extraction System (cTAKES): architecture, component evaluation and applications

paper_content:

We aim to build and evaluate an open-source natural language processing system for information extraction from electronic medical record clinical free-text. We describe and evaluate our system, the clinical Text Analysis and Knowledge Extraction System (cTAKES), released open-source at . The cTAKES builds on existing open-source technologies—the Unstructured Information Management Architecture framework and OpenNLP natural language processing toolkit. Its components, specifically trained for the clinical domain, create rich linguistic and semantic annotations. Performance of individual components: sentence boundary detector accuracy=0.949; tokenizer accuracy=0.949; part-of-speech tagger accuracy=0.936; shallow parser F-score=0.924; named entity recognizer and system-level evaluation F-score=0.715 for exact and 0.824 for overlapping spans, and accuracy for concept mapping, negation, and status attributes for exact and overlapping spans of 0.957, 0.943, 0.859, and 0.580, 0.939, and 0.839, respectively. Overall performance is discussed against five applications. The cTAKES annotations are the foundation for methods and modules for higher-level semantic processing of clinical free-text.
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paper_title: Ontology-Based Knowledge Discovery in Pharmacogenomics

paper_content:

One current challenge in biomedicine is to analyze large amounts of complex biological data for extracting domain knowledge. This work holds on the use of knowledge-based techniques such as knowledge discovery (KD) and knowledge representation (KR) in pharmacogenomics, where knowledge units represent genotype–phenotype relationships in the context of a given treatment. An objective is to design knowledge base (KB, here also mentioned as an ontology) and then to use it in the KD process itself. A method is proposed for dealing with two main tasks: (1) building a KB from heterogeneous data related to genotype, phenotype, and treatment, and (2) applying KD techniques on knowledge assertions for extracting genotype–phenotype relationships. An application was carried out on a clinical trial concerned with the variability of drug response to montelukast treatment. Genotype–genotype and genotype–phenotype associations were retrieved together with new associations, allowing the extension of the initial KB. This experiment shows the potential of KR and KD processes, especially for designing KB, checking KB consistency, and reasoning for problem solving.
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paper_title: Methodological Review: Coreference resolution: A review of general methodologies and applications in the clinical domain

paper_content:

Coreference resolution is the task of determining linguistic expressions that refer to the same real-world entity in natural language. Research on coreference resolution in the general English domain dates back to 1960s and 1970s. However, research on coreference resolution in the clinical free text has not seen major development. The recent US government initiatives that promote the use of electronic health records (EHRs) provide opportunities to mine patient notes as more and more health care institutions adopt EHR. Our goal was to review recent advances in general purpose coreference resolution to lay the foundation for methodologies in the clinical domain, facilitated by the availability of a shared lexical resource of gold standard coreference annotations, the Ontology Development and Information Extraction (ODIE) corpus.
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paper_title: Resolving anaphoras for the extraction of drug-drug interactions in pharmacological documents

paper_content:

Background ::: Drug-drug interactions are frequently reported in the increasing amount of biomedical literature. Information Extraction (IE) techniques have been devised as a useful instrument to manage this knowledge. Nevertheless, IE at the sentence level has a limited effect because of the frequent references to previous entities in the discourse, a phenomenon known as 'anaphora'. DrugNerAR, a drug anaphora resolution system is presented to address the problem of co-referring expressions in pharmacological literature. This development is part of a larger and innovative study about automatic drug-drug interaction extraction.
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paper_title: The Evaluation of a Temporal Reasoning System in Processing Clinical Discharge Summaries

paper_content:

Abstract Context TimeText is a temporal reasoning system designed to represent, extract, and reason about temporal information in clinical text. Objective To measure the accuracy of the TimeText for processing clinical discharge summaries. Design Six physicians with biomedical informatics training served as domain experts. Twenty discharge summaries were randomly selected for the evaluation. For each of the first 14 reports, 5 to 8 clinically important medical events were chosen. The temporal reasoning system generated temporal relations about the endpoints (start or finish) of pairs of medical events. Two experts (subjects) manually generated temporal relations for these medical events. The system and expert-generated results were assessed by four other experts (raters). All of the twenty discharge summaries were used to assess the system’s accuracy in answering time-oriented clinical questions. For each report, five to ten clinically plausible temporal questions about events were generated. Two experts generated answers to the questions to serve as the gold standard. We wrote queries to retrieve answers from system’s output. Measurements Correctness of generated temporal relations, recall of clinically important relations, and accuracy in answering temporal questions. Results The raters determined that 97% of subjects’ 295 generated temporal relations were correct and that 96.5% of the system’s 995 generated temporal relations were correct. The system captured 79% of 307 temporal relations determined to be clinically important by the subjects and raters. The system answered 84% of the temporal questions correctly. Conclusion The system encoded the majority of information identified by experts, and was able to answer simple temporal questions.
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paper_title: Linking entries in protein interaction database to structured text: the FEBS Letters experiment.

paper_content:

The corpus of the scientific literature has reached such size that a lot of useful data, dispersed throughout millions different articles, are now hard to recover. For instance, many articles in the biological domain describe relationships between entities (gene, proteins, small molecules, etc.) yet this crucial information cannot be efficiently used because of the difficulties in retrieving it automatically from unstructured text. Databases are striving to capture this valuable information and to organize it in a structured format ready for automatic analysis. However, the current database model, based on manual curation, is not sustainable because the limited support is not compatible with complete and accurate coverage of published information. Several proposals have been put forward to increase the efficiency and accuracy of the curation process. Here we present an experiment, designed by the editorial board of FEBS Letters, aimed at integrating each manuscript with a structured summary precisely reporting, with database identifiers and predefined controlled vocabularies, the protein interactions reported in the manuscript. The authors play an important role in this process as they are requested to provide structured information to be appended, in the form of human-readable paragraphs, at the end of traditional summaries. It is envisaged that the structured text will become an integral part of Medline abstracts. In 6 months time the experience gained with this experiment will form the basis for a community discussion to propose a widely accepted strategy for information storage and retrieval.
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paper_title: Towards Domain-Independent Argumentative Zoning: Evidence from Chemistry and Computational Linguistics

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Argumentative Zoning (AZ) is an analysis of the argumentative and rhetorical structure of a scientific paper. It has been shown to be reliably used by independent human coders, and has proven useful for various information access tasks. Annotation experiments have however so far been restricted to one discipline, computational linguistics (CL). Here, we present a more informative AZ scheme with 15 categories in place of the original 7, and show that it can be applied to the life sciences as well as to CL. We use a domain expert to encode basic knowledge about the subject (such as terminology and domain specific rules for individual categories) as part of the annotation guidelines. Our results show that non-expert human coders can then use these guidelines to reliably annotate this scheme in two domains, chemistry and computational linguistics.
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paper_title: The biomedical discourse relation bank

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BackgroundIdentification of discourse relations, such as causal and contrastive relations, between situations mentioned in text is an important task for biomedical text-mining. A biomedical text corpus annotated with discourse relations would be very useful for developing and evaluating methods for biomedical discourse processing. However, little effort has been made to develop such an annotated resource.ResultsWe have developed the Biomedical Discourse Relation Bank (BioDRB), in which we have annotated explicit and implicit discourse relations in 24 open-access full-text biomedical articles from the GENIA corpus. Guidelines for the annotation were adapted from the Penn Discourse TreeBank (PDTB), which has discourse relations annotated over open-domain news articles. We introduced new conventions and modifications to the sense classification. We report reliable inter-annotator agreement of over 80% for all sub-tasks. Experiments for identifying the sense of explicit discourse connectives show the connective itself as a highly reliable indicator for coarse sense classification (accuracy 90.9% and F1 score 0.89). These results are comparable to results obtained with the same classifier on the PDTB data. With more refined sense classification, there is degradation in performance (accuracy 69.2% and F1 score 0.28), mainly due to sparsity in the data. The size of the corpus was found to be sufficient for identifying the sense of explicit connectives, with classifier performance stabilizing at about 1900 training instances. Finally, the classifier performs poorly when trained on PDTB and tested on BioDRB (accuracy 54.5% and F1 score 0.57).ConclusionOur work shows that discourse relations can be reliably annotated in biomedical text. Coarse sense disambiguation of explicit connectives can be done with high reliability by using just the connective as a feature, but more refined sense classification requires either richer features or more annotated data. The poor performance of a classifier trained in the open domain and tested in the biomedical domain suggests significant differences in the semantic usage of connectives across these domains, and provides robust evidence for a biomedical sublanguage for discourse and the need to develop a specialized biomedical discourse annotated corpus. The results of our cross-domain experiments are consistent with related work on identifying connectives in BioDRB.
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paper_title: The structural and content aspects of abstracts versus bodies of full text journal articles are different

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BackgroundAn increase in work on the full text of journal articles and the growth of PubMedCentral have the opportunity to create a major paradigm shift in how biomedical text mining is done. However, until now there has been no comprehensive characterization of how the bodies of full text journal articles differ from the abstracts that until now have been the subject of most biomedical text mining research.ResultsWe examined the structural and linguistic aspects of abstracts and bodies of full text articles, the performance of text mining tools on both, and the distribution of a variety of semantic classes of named entities between them. We found marked structural differences, with longer sentences in the article bodies and much heavier use of parenthesized material in the bodies than in the abstracts. We found content differences with respect to linguistic features. Three out of four of the linguistic features that we examined were statistically significantly differently distributed between the two genres. We also found content differences with respect to the distribution of semantic features. There were significantly different densities per thousand words for three out of four semantic classes, and clear differences in the extent to which they appeared in the two genres. With respect to the performance of text mining tools, we found that a mutation finder performed equally well in both genres, but that a wide variety of gene mention systems performed much worse on article bodies than they did on abstracts. POS tagging was also more accurate in abstracts than in article bodies.ConclusionsAspects of structure and content differ markedly between article abstracts and article bodies. A number of these differences may pose problems as the text mining field moves more into the area of processing full-text articles. However, these differences also present a number of opportunities for the extraction of data types, particularly that found in parenthesized text, that is present in article bodies but not in article abstracts.
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paper_title: Synthesis of Pharmacokinetic Pathways through Knowledge Acquisition and Automated Reasoning

paper_content:

Biological pathways are seen as highly critical in our understanding of the mechanism of biological functions. To collect information about pathways, manual curation has been the most popular method. However, pathway annotation is regarded as heavily timeconsuming, as it requires expert curators to identify and collect information from different sources. Even with the pieces of biological facts and interactions collected from various sources, curators have to apply their biological knowledge to arrange the acquired interactions in such a way that together they perform a common biological function as a pathway. In this paper, we propose a novel approach for automated pathway synthesis that acquires facts from hand-curated knowledge bases. To comprehend the incompleteness of the knowledge bases, our approach also obtains facts through automated extraction from Medline abstracts. An essential component of our approach is to apply logical reasoning to the acquired facts based on the biological knowledge about pathways. By representing such biological knowledge, the reasoning component is capable of assigning ordering to the acquired facts and interactions that is necessary for pathway synthesis. We demonstrate the feasibility of our approach with the development of a system that synthesizes pharmacokinetic pathways. We evaluate our approach by reconstructing the existing pharmacokinetic pathways available in PharmGKB. Our results show that not only that our approach is capable of synthesizing these pathways but also uncovering information that is not available in the manually annotated pathways.
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paper_title: Automated concept-level information extraction to reduce the need for custom software and rules development

paper_content:

Objective Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval. ::: ::: Materials and methods A ‘learn by example’ approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance. ::: ::: Results Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks. ::: ::: Discussion With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation. ::: ::: Conclusion Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download.
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paper_title: Beyond genes, proteins, and abstracts: Identifying scientific claims from full-text biomedical articles

paper_content:

Massive increases in electronically available text have spurred a variety of natural language processing methods to automatically identify relationships from text; however, existing annotated collections comprise only bioinformatics (gene-protein) or clinical informatics (treatment-disease) relationships. This paper introduces the Claim Framework that reflects how authors across biomedical spectrum communicate findings in empirical studies. The Framework captures different levels of evidence by differentiating between explicit and implicit claims, and by capturing under-specified claims such as correlations, comparisons, and observations. The results from 29 full-text articles show that authors report fewer than 7.84% of scientific claims in an abstract, thus revealing the urgent need for text mining systems to consider the full-text of an article rather than just the abstract. The results also show that authors typically report explicit claims (77.12%) rather than an observations (9.23%), correlations (5.39%), comparisons (5.11%) or implicit claims (2.7%). Informed by the initial manual annotations, we introduce an automated approach that uses syntax and semantics to identify explicit claims automatically and measure the degree to which each feature contributes to the overall precision and recall. Results show that a combination of semantics and syntax is required to achieve the best system performance.
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paper_title: Manual curation is not sufficient for annotation of genomic databases

paper_content:

Motivation: Knowledge base construction has been an area of intense activity and great importance in the growth of computational biology. However, there is little or no history of work on the subject of evaluation of knowledge bases, either with respect to their contents or with respect to the processes by which they are constructed. This article proposes the application of a metric from software engineering known as the found/fixed graph to the problem of evaluating the processes by which genomic knowledge bases are built, as well as the completeness of their contents. ::: ::: Results: Well-understood patterns of change in the found/fixed graph are found to occur in two large publicly available knowledge bases. These patterns suggest that the current manual curation processes will take far too long to complete the annotations of even just the most important model organisms, and that at their current rate of production, they will never be sufficient for completing the annotation of all currently available proteomes. ::: ::: Contact: larry.hunter@uchsc.edu
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paper_title: Challenges for extracting biomedical knowledge from full text

paper_content:

At present, most biomedical Information Retrieval and Extraction tools process abstracts rather than full-text articles. The increasing availability of full text will allow more knowledge to be extracted with greater reliability. To investigate the challenges of full-text processing, we manually annotated a corpus of cited articles from a Molecular Interaction Map (Kohn, 1999). ::: ::: Our analysis demonstrates the necessity of full-text processing; identifies the article sections where interactions are most commonly stated; and quantifies both the amount of external knowledge required and the proportion of interactions requiring multiple or deeper inference steps. Further, it identifies a range of NLP tools required, including: identifying synonyms, and resolving coreference and negated expressions. This is important guidance for researchers engineering biomedical text processing systems.
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paper_title: Towards pharmacogenomics knowledge discovery with the semantic web

paper_content:

Pharmacogenomics aims to understand pharmacological response with respect to genetic variation. Essential to the delivery of better health care is the use of pharmacogenomics knowledge to answer questions about therapeutic, pharmacological or genetic aspects. Several XML markup languages have been developed to capture pharmacogenomic and related information so as to facilitate data sharing. However, recent advances in semantic web technologies have presented exciting new opportunities for pharmacogenomics knowledge discovery by representing the information with machine understandable semantics. Progress in this area is illustrated with reference to the personalized medicine project that aims to facilitate pharmacogenomics knowledge discovery through intuitive knowledge capture and sophisticated question answering using automated reasoning over expressive ontologies.
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paper_title: A temporal constraint structure for extracting temporal information from clinical narrative

paper_content:

Introduction. Time is an essential element in medical data and knowledge which is intrinsically connected with medical reasoning tasks. Many temporal reasoning mechanisms use constraint-based approaches. Our previous research demonstrates that electronic discharge summaries can be modeled as a simple temporal problem (STP).Objective. To categorize temporal expressions in clinical narrative text and to propose and evaluate a temporal constraint structure designed to model this temporal information and to support the implementation of higher-level temporal reasoning.Methods. A corpus of 200 random discharge summaries across 18 years was applied in a grounded approach to construct a representation structure. Then, a subset of 100 discharge summaries was used to tally the frequency of each identified time category and the percentage of temporal expressions modeled by the structure. Fifty random expressions were used to assess inter-coder agreement.Results. Six main categories of temporal expressions were identified. The constructed temporal constraint structure models time over which an event occurs by constraining its starting time and ending time. It includes a set of fields for the endpoint(s) of an event, anchor information, qualitative and metric temporal relations, and vagueness. In 100 discharge summaries, 1961 of 2022 (97%) identified temporal expressions were effectively modeled using the temporal constraint structure. Inter-coder evaluation of 50 expressions yielded exact match in 90%, partial match with trivial differences in 8%, partial match with large differences in 2%, and total mismatch in 0%.Conclusion. The proposed temporal constraint structure embodies a sufficient and successful implementation method to encode the diversity of temporal information in discharge summaries. Placing data within the structure provides a foundational representation upon which further reasoning, including the addition of domain knowledge and other post-processing to implement an STP, can be accomplished.
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paper_title: Integration and publication of heterogeneous text-mined relationships on the Semantic Web

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BackgroundAdvances in Natural Language Processing (NLP) techniques enable the extraction of fine-grained relationships mentioned in biomedical text. The variability and the complexity of natural language in expressing similar relationships causes the extracted relationships to be highly heterogeneous, which makes the construction of knowledge bases difficult and poses a challenge in using these for data mining or question answering.ResultsWe report on the semi-automatic construction of the PHARE relationship ontology (the PHArmacogenomic RElationships Ontology) consisting of 200 curated relations from over 40,000 heterogeneous relationships extracted via text-mining. These heterogeneous relations are then mapped to the PHARE ontology using synonyms, entity descriptions and hierarchies of entities and roles. Once mapped, relationships can be normalized and compared using the structure of the ontology to identify relationships that have similar semantics but different syntax. We compare and contrast the manual procedure with a fully automated approach using WordNet to quantify the degree of integration enabled by iterative curation and refinement of the PHARE ontology. The result of such integration is a repository of normalized biomedical relationships, named PHARE-KB, which can be queried using Semantic Web technologies such as SPARQL and can be visualized in the form of a biological network.ConclusionsThe PHARE ontology serves as a common semantic framework to integrate more than 40,000 relationships pertinent to pharmacogenomics. The PHARE ontology forms the foundation of a knowledge base named PHARE-KB. Once populated with relationships, PHARE-KB (i) can be visualized in the form of a biological network to guide human tasks such as database curation and (ii) can be queried programmatically to guide bioinformatics applications such as the prediction of molecular interactions. PHARE is available at http://purl.bioontology.org/ontology/PHARE.
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paper_title: MutationFinder: a high-performance system for extracting point mutation mentions from text

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Summary ::: Discussion of point mutations is ubiquitous in biomedical literature, and manually compiling databases or literature on mutations in specific genes or proteins is tedious. We present an open-source, rule-based system, MutationFinder, for extracting point mutation mentions from text. On blind test data, it achieves nearly perfect precision and a markedly improved recall over a baseline.
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paper_title: Anaphoric relations in the clinical narrative: corpus creation

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Objective The long-term goal of this work is the automated discovery of anaphoric relations from the clinical narrative. The creation of a gold standard set from a cross-institutional corpus of clinical notes and high-level characteristics of that gold standard are described. ::: ::: Methods A standard methodology for annotation guideline development, gold standard annotations, and inter-annotator agreement (IAA) was used. ::: ::: Results The gold standard annotations resulted in 7214 markables, 5992 pairs, and 1304 chains. Each report averaged 40 anaphoric markables, 33 pairs, and seven chains. The overall IAA is high on the Mayo dataset (0.6607), and moderate on the University of Pittsburgh Medical Center (UPMC) dataset (0.4072). The IAA between each annotator and the gold standard is high (Mayo: 0.7669, 0.7697, and 0.9021; UPMC: 0.6753 and 0.7138). These results imply a quality corpus feasible for system development. They also suggest the complementary nature of the annotations performed by the experts and the importance of an annotator team with diverse knowledge backgrounds. ::: ::: Limitations Only one of the annotators had the linguistic background necessary for annotation of the linguistic attributes. The overall generalizability of the guidelines will be further strengthened by annotations of data from additional sites. This will increase the overall corpus size and the representation of each relation type. ::: ::: Conclusion The first step toward the development of an anaphoric relation resolver as part of a comprehensive natural language processing system geared specifically for the clinical narrative in the electronic medical record is described. The deidentified annotated corpus will be available to researchers.
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paper_title: OSIRISv1.2: A named entity recognition system for sequence variants of genes in biomedical literature

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BackgroundSingle Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required.ResultsOur group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes http://ibi.imim.es/osirisform.html. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, http://ibi.imim.es/OSIRISv1.2.html) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented.ConclusionOSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.
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paper_title: Ontology-guided data preparation for discovering genotype-phenotype relationships

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BackgroundComplexity and amount of post-genomic data constitute two major factors limiting the application of Knowledge Discovery in Databases (KDD) methods in life sciences. Bio-ontologies may nowadays play key roles in knowledge discovery in life science providing semantics to data and to extracted units, by taking advantage of the progress of Semantic Web technologies concerning the understanding and availability of tools for knowledge representation, extraction, and reasoning.ResultsThis paper presents a method that exploits bio-ontologies for guiding data selection within the preparation step of the KDD process. We propose three scenarios in which domain knowledge and ontology elements such as subsumption, properties, class descriptions, are taken into account for data selection, before the data mining step. Each of these scenarios is illustrated within a case-study relative to the search of genotype-phenotype relationships in a familial hypercholesterolemia dataset. The guiding of data selection based on domain knowledge is analysed and shows a direct influence on the volume and significance of the data mining results.ConclusionsThe method proposed in this paper is an efficient alternative to numerical methods for data selection based on domain knowledge. In turn, the results of this study may be reused in ontology modelling and data integration.
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paper_title: Suggested Ontology for Pharmacogenomics (SO-Pharm): Modular Construction and Preliminary Testing

paper_content:

Pharmacogenomics studies the involvement of interindividual variations of DNA sequence in different drug responses (especially adverse drug reactions) Knowledge Discovery in Databases (KDD) process is a means for discovering new pharmacogenomic knowledge in biological databases However data complexity makes it necessary to guide the KDD process by representation of domain knowledge Three domains at least are in concern: genotype, drug and phenotype The approach described here aims at reusing whenever possible existing domain knowledge in order to build a modular formal representation of domain knowledge in pharmacogenomics The resulting ontology is called SO-Pharm for Suggested Ontology for Pharmacogenomics Various situations encountered during the construction process are analyzed and discussed A preliminary validation is provided by representing with SO-Pharm concepts some well-known examples of pharmacogenomic knowledge.
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paper_title: Using literature-based discovery to identify disease candidate genes

paper_content:

We present BITOLA, an interactive literature-based biomedical discovery support system. The goal of this system is to discover new, potentially meaningful relations between a given starting concept of interest and other concepts, by mining the bibliographic database MEDLINE. To make the system more suitable for disease candidate gene discovery and to decrease the number of candidate relations, we integrate background knowledge about the chromosomal location of the starting disease as well as the chromosomal location of the candidate genes from resources such as LocusLink and Human Genome Organization (HUGO). BITOLA can also be used as an alternative way of searching the MEDLINE database. The system is available at http://www.mf.uni-lj.si/bitola/.
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paper_title: Discovering drug–drug interactions: a text-mining and reasoning approach based on properties of drug metabolism

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Motivation: Identifying drug–drug interactions (DDIs) is a critical process in drug administration and drug development. Clinical support tools often provide comprehensive lists of DDIs, but they usually lack the supporting scientific evidences and different tools can return inconsistent results. In this article, we propose a novel approach that integrates text mining and automated reasoning to derive DDIs. Through the extraction of various facts of drug metabolism, not only the DDIs that are explicitly mentioned in text can be extracted but also the potential interactions that can be inferred by reasoning. ::: ::: Results: Our approach was able to find several potential DDIs that are not present in DrugBank. We manually evaluated these interactions based on their supporting evidences, and our analysis revealed that 81.3% of these interactions are determined to be correct. This suggests that our approach can uncover potential DDIs with scientific evidences explaining the mechanism of the interactions. ::: ::: Contact: luis.tari@roche.com
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paper_title: Statistical Anaphora Resolution in Biomedical Texts

paper_content:

This paper presents a probabilistic model for resolution of non-pronominal anaphora in biomedical texts. The model seeks to find the antecedents of anaphoric expressions, both coreferent and associative ones, and also to identify discourse-new expressions. We consider only the noun phrases referring to biomedical entities. The model reaches state-of-the art performance: 56--69% precision and 54--67% recall on coreferent cases, and reasonable performance on different classes of associative cases.
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paper_title: Abductive reasoning: Logic, visual thinking, and coherence

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This paper discusses abductive reasoning—that is, reasoning in which explanatory hypotheses are formed and evaluated. First, it criticizes two recent formal logical models of abduction. An adequate formalization would have to take into account the following aspects of abduction: explanation is not deduction; hypotheses are layered; abduction is sometimes creative; hypotheses may be revolutionary; completeness is elusive; simplicity is complex; and abductive reasoning may be visual and non-sentential. Second, in order to illustrate visual aspects of hypothesis formation, the paper describes recent work on visual inference in archaeology. Third, in connection with the evaluation of explanatory hypotheses, the paper describes recent results on the computation of coherence.
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paper_title: Nominalization and Alternations in Biomedical Language

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Background ::: This paper presents data on alternations in the argument structure of common domain-specific verbs and their associated verbal nominalizations in the PennBioIE corpus. Alternation is the term in theoretical linguistics for variations in the surface syntactic form of verbs, e.g. the different forms of stimulate in FSH stimulates follicular development and follicular development is stimulated by FSH. The data is used to assess the implications of alternations for biomedical text mining systems and to test the fit of the sublanguage model to biomedical texts.
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Title: Mining the pharmacogenomics literature—a survey of the state of the art

Section 1: INTRODUCTION
Description 1: Provide an overview of the pharmacogenomics field, its relation to individualized medicine, the challenges of integrating data from various biomedical disciplines, and the emergence of pharmacogenomic text mining.

Section 2: MINING THE PHARMACOGENOMICS LITERATURE
Description 2: Review the most recent results in automatically mining the pharmacogenomics literature, categorizing named entity identification and relation extraction across genotype, phenotype, and pharmacological levels.

Section 3: Genotype mining
Description 3: Discuss methods and research efforts focused on identifying and normalizing genotype-related named entities like genes and proteins and their interactions.

Section 4: Phenotype mining
Description 4: Review techniques for extracting phenotype-related data, focusing on diseases, pathological phenomena, and treatment-related information from various text sources.

Section 5: Mining pharmacological information
Description 5: Present approaches to identifying and extracting information about drugs and other chemicals, emphasizing therapy-related chemicals and their interactions.

Section 6: Genotype^phenotype mining
Description 6: Explore the intersection of genotypic and phenotypic data, discussing research that combines gene/protein and disease-related mining.

Section 7: Genotype^drug mining
Description 7: Analyze methods for connecting genetic data to drug efficacy and interactions, essential for personalized medicine and adverse effect prediction.

Section 8: Phenotype^drug mining
Description 8: Investigate how drugs affect phenotypic states, including adverse drug reactions and therapy outcomes, focusing on clinical and biomedical text sources.

Section 9: Genotype^phenotype^drug mining
Description 9: Discuss comprehensive methods that integrate genotypic, phenotypic, and drug data, highlighting their role in pharmacogenomic research.

Section 10: Knowledge discovery: mining implicit and novel information
Description 10: Outline methodologies focused on uncovering implicit and novel knowledge from texts, using distributional characteristics and logical reasoning.

Section 11: Summarizing remarks on text mining approaches
Description 11: Summarize various text mining methodologies, their application in biomedical research, and performance evaluation metrics.

Section 12: INFRASTRUCTURE RELEVANT FOR MINING THE PHARMACOGENOMICS LITERATURE
Description 12: Elaborate on the infrastructural components necessary for pharmacogenomic text mining including annotated corpora, terminologies, ontologies, software frameworks, and visualization tools.

Section 13: Annotated corpora
Description 13: Provide details on the creation, use, and significance of annotated corpora in developing and evaluating text mining systems.

Section 14: Genotype-focused corpora
Description 14: Discuss specific corpora dedicated to genotypic data, their content, and their importance in text mining for pharmacogenomics.

Section 15: Phenotype-focused corpora
Description 15: Review corpora focused on phenotypic information, highlighting those derived from clinical notes and other medical records.

Section 16: Drug-and chemicals-focused corpora
Description 16: Outline specialized corpora that annotate drug and chemical data across different text genres, including scientific publications and clinical records.

Section 17: Terminologies and ontologies
Description 17: Describe the role of terminologies and ontologies in pharmacogenomic text mining, including key resources for genotypes, phenotypes, and drugs.

Section 18: Software infrastructure
Description 18: Present the software frameworks and tools that support pharmacogenomic text mining, including UIMA and ontology-based systems.

Section 19: Disseminating and presenting the results of text mining
Description 19: Discuss approaches for presenting text mining results to the biomedical community, focusing on web services, visualization tools, and integration with existing analysis platforms.

Section 20: APPLICATIONS
Description 20: Outline various applications of pharmacogenomic text mining, such as candidate gene ranking, drug-drug interaction prediction, adverse drug effect analysis, and curation guidance.

Section 21: CONCLUSIONS AND OUTLOOK
Description 21: Summarize the current state and future prospects of pharmacogenomic text mining, addressing challenges in full-text analytics, knowledge discovery, and deeper text reasoning.

Section 22: Key Points
Description 22: Highlight the main takeaways from the survey, including the importance of text mining for pharmacogenomics, available resources and tools, and emerging research opportunities.