A survey on Big Data and Machine Learning for Chemistry
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paper_title: Microwave-assisted parallel synthesis of benzofuran-2-carboxamide derivatives bearing anti-inflammatory, analgesic and antipyretic agents

paper_content:

Abstract A series of benzofuran-2-carboxamides of biological and medicinal significance were synthesized by a microwave-assisted one-pot parallel approach via O-alkylation/Knoevenagel condensation. All the compounds were characterized and assayed for their in vivo anti-inflammatory, analgesic and antipyretic activities. The activity data of all compounds were listed and discussed in detail, among which some derivatives exhibited potent activities of particular interest.
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paper_title: Managing the computational chemistry big data problem: the ioChem-BD platform.

paper_content:

We present the ioChem-BD platform (www.iochem-bd.org) as a multiheaded tool aimed to manage large volumes of quantum chemistry results from a diverse group of already common simulation packages. The platform has an extensible structure. The key modules managing the main tasks are to (i) upload of output files from common computational chemistry packages, (ii) extract meaningful data from the results, and (iii) generate output summaries in user-friendly formats. A heavy use of the Chemical Mark-up Language (CML) is made in the intermediate files used by ioChem-BD. From them and using XSL techniques, we manipulate and transform such chemical data sets to fulfill researchers’ needs in the form of HTML5 reports, supporting information, and other research media.
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paper_title: On the role of words in the network structure of texts: application to authorship attribution

paper_content:

Well-established automatic analyses of texts mainly consider frequencies of linguistic units, e.g. letters, words and bigrams, while methods based on co-occurrence networks consider the structure of texts regardless of the nodes label (i.e. the words semantics). In this paper, we reconcile these distinct viewpoints by introducing a generalized similarity measure to compare texts which accounts for both the network structure of texts and the role of individual words in the networks. We use the similarity measure for authorship attribution of three collections of books, each composed of 8 authors and 10 books per author. High accuracy rates were obtained with typical values from 90% to 98.75%, much higher than with the traditional the TF-IDF approach for the same collections. These accuracies are also higher than taking only the topology of networks into account. We conclude that the different properties of specific words on the macroscopic scale structure of a whole text are as relevant as their frequency of appearance; conversely, considering the identity of nodes brings further knowledge about a piece of text represented as a network.
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paper_title: High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response

paper_content:

Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.
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paper_title: Big Data from Pharmaceutical Patents: A Computational Analysis of Medicinal Chemists' Bread and Butter.

paper_content:

Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reaction schemes, including reaction roles and yields, from pharmaceutical patents. The reactions were assigned to well-known reaction types such as Wittig olefination or Buchwald-Hartwig amination using an expert system. Analyzing the evolution of reaction types over time, we observe the previously reported bias toward reaction classes like amide bond formations or Suzuki couplings. Our study also shows a steady increase in the number of different reaction types used in pharmaceutical patents but a trend toward lower median yield for some of the reaction classes. Finally, we found that today's typical product molecule is larger, more hydrophobic, and more rigid than 40 years ago.
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paper_title: Enriching Complex Networks with Word Embeddings for Detecting Mild Cognitive Impairment from Speech Transcripts

paper_content:

Mild Cognitive Impairment (MCI) is a mental disorder difficult to diagnose. Linguistic features, mainly from parsers, have been used to detect MCI, but this is not suitable for large-scale assessments. MCI disfluencies produce non-grammatical speech that requires manual or high precision automatic correction of transcripts. In this paper, we modeled transcripts into complex networks and enriched them with word embedding (CNE) to better represent short texts produced in neuropsychological assessments. The network measurements were applied with well-known classifiers to automatically identify MCI in transcripts, in a binary classification task. A comparison was made with the performance of traditional approaches using Bag of Words (BoW) and linguistic features for three datasets: DementiaBank in English, and Cinderella and Arizona-Battery in Portuguese. Overall, CNE provided higher accuracy than using only complex networks, while Support Vector Machine was superior to other classifiers. CNE provided the highest accuracies for DementiaBank and Cinderella, but BoW was more efficient for the Arizona-Battery dataset probably owing to its short narratives. The approach using linguistic features yielded higher accuracy if the transcriptions of the Cinderella dataset were manually revised. Taken together, the results indicate that complex networks enriched with embedding is promising for detecting MCI in large-scale assessments
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paper_title: BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology

paper_content:

BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole.
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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: Deep learning

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Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. Because the computer gathers knowledge from experience, there is no need for a human computer operator to formally specify all the knowledge that the computer needs. The hierarchy of concepts allows the computer to learn complicated concepts by building them out of simpler ones; a graph of these hierarchies would be many layers deep. This book introduces a broad range of topics in deep learning. The text offers mathematical and conceptual background, covering relevant concepts in linear algebra, probability theory and information theory, numerical computation, and machine learning. It describes deep learning techniques used by practitioners in industry, including deep feedforward networks, regularization, optimization algorithms, convolutional networks, sequence modeling, and practical methodology; and it surveys such applications as natural language processing, speech recognition, computer vision, online recommendation systems, bioinformatics, and videogames. Finally, the book offers research perspectives, covering such theoretical topics as linear factor models, autoencoders, representation learning, structured probabilistic models, Monte Carlo methods, the partition function, approximate inference, and deep generative models. Deep Learning can be used by undergraduate or graduate students planning careers in either industry or research, and by software engineers who want to begin using deep learning in their products or platforms. A website offers supplementary material for both readers and instructors.
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paper_title: Gradient-Based Learning Applied to Document Recognition

paper_content:

Multilayer neural networks trained with the back-propagation algorithm constitute the best example of a successful gradient based learning technique. Given an appropriate network architecture, gradient-based learning algorithms can be used to synthesize a complex decision surface that can classify high-dimensional patterns, such as handwritten characters, with minimal preprocessing. This paper reviews various methods applied to handwritten character recognition and compares them on a standard handwritten digit recognition task. Convolutional neural networks, which are specifically designed to deal with the variability of 2D shapes, are shown to outperform all other techniques. Real-life document recognition systems are composed of multiple modules including field extraction, segmentation recognition, and language modeling. A new learning paradigm, called graph transformer networks (GTN), allows such multimodule systems to be trained globally using gradient-based methods so as to minimize an overall performance measure. Two systems for online handwriting recognition are described. Experiments demonstrate the advantage of global training, and the flexibility of graph transformer networks. A graph transformer network for reading a bank cheque is also described. It uses convolutional neural network character recognizers combined with global training techniques to provide record accuracy on business and personal cheques. It is deployed commercially and reads several million cheques per day.
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paper_title: Comparative Study of Deep Learning Software Frameworks

paper_content:

Deep learning methods have resulted in significant performance improvements in several application domains and as such several software frameworks have been developed to facilitate their implementation. This paper presents a comparative study of five deep learning frameworks, namely Caffe, Neon, TensorFlow, Theano, and Torch, on three aspects: extensibility, hardware utilization, and speed. The study is performed on several types of deep learning architectures and we evaluate the performance of the above frameworks when employed on a single machine for both (multi-threaded) CPU and GPU (Nvidia Titan X) settings. The speed performance metrics used here include the gradient computation time, which is important during the training phase of deep networks, and the forward time, which is important from the deployment perspective of trained networks. For convolutional networks, we also report how each of these frameworks support various convolutional algorithms and their corresponding performance. From our experiments, we observe that Theano and Torch are the most easily extensible frameworks. We observe that Torch is best suited for any deep architecture on CPU, followed by Theano. It also achieves the best performance on the GPU for large convolutional and fully connected networks, followed closely by Neon. Theano achieves the best performance on GPU for training and deployment of LSTM networks. Caffe is the easiest for evaluating the performance of standard deep architectures. Finally, TensorFlow is a very flexible framework, similar to Theano, but its performance is currently not competitive compared to the other studied frameworks.
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paper_title: Deep Learning for Computational Chemistry

paper_content:

The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non-neural networks state-of-the-art models across disparate research topics, and deep neural network-based models often exceeded the “glass ceiling” expectations of their respective tasks. Coupled with the maturity of GPU-accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.
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paper_title: Imagenet classification with deep convolutional neural networks

paper_content:

We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0% which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overriding in the fully-connected layers we employed a recently-developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.
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paper_title: Neural network based recognition of flow injection patterns

paper_content:

Response patterns produced from a flow injection (FI) system employing sodium, potassium and calcium ion-selective electrodes as detectors were used for training and testing back-propagation neural networks. A variety of different network parameters were investigated including a study of the effects of variation of the learning rate coefficient and the momentum on the rate of training. The networks studied demonstrated the ability to recognize the identity of sample components even in FI patterns severely distorted by noise addition, peak height variation and baseline shift.
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paper_title: Learning from the Harvard Clean Energy Project: The Use of Neural Networks to Accelerate Materials Discovery

paper_content:

Here, the employment of multilayer perceptrons, a type of artificial neural network, is proposed as part of a computational funneling procedure for high-throughput organic materials design. Through the use of state of the art algorithms and a large amount of data extracted from the Harvard Clean Energy Project, it is demonstrated that these methods allow a great reduction in the fraction of the screening library that is actually calculated. Neural networks can reproduce the results of quantum-chemical calculations with a large level of accuracy. The proposed approach allows to carry out large-scale molecular screening projects with less computational time. This, in turn, allows for the exploration of increasingly large and diverse libraries.
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paper_title: Comparison of Deep Learning With Multiple Machine Learning Methods and Metrics Using Diverse Drug Discovery Data Sets

paper_content:

Machine learning methods have been applied to many data sets in pharmaceutical research for several decades. The relative ease and availability of fingerprint type molecular descriptors paired with Bayesian methods resulted in the widespread use of this approach for a diverse array of end points relevant to drug discovery. Deep learning is the latest machine learning algorithm attracting attention for many of pharmaceutical applications from docking to virtual screening. Deep learning is based on an artificial neural network with multiple hidden layers and has found considerable traction for many artificial intelligence applications. We have previously suggested the need for a comparison of different machine learning methods with deep learning across an array of varying data sets that is applicable to pharmaceutical research. End points relevant to pharmaceutical research include absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, as well as activity against pathogens and ...
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paper_title: The Next Era: Deep Learning in Pharmaceutical Research

paper_content:

Over the past decade we have witnessed the increasing sophistication of machine learning algorithms applied in daily use from internet searches, voice recognition, social network software to machine vision software in cameras, phones, robots and self-driving cars. Pharmaceutical research has also seen its fair share of machine learning developments. For example, applying such methods to mine the growing datasets that are created in drug discovery not only enables us to learn from the past but to predict a molecule's properties and behavior in future. The latest machine learning algorithm garnering significant attention is deep learning, which is an artificial neural network with multiple hidden layers. Publications over the last 3 years suggest that this algorithm may have advantages over previous machine learning methods and offer a slight but discernable edge in predictive performance. The time has come for a balanced review of this technique but also to apply machine learning methods such as deep learning across a wider array of endpoints relevant to pharmaceutical research for which the datasets are growing such as physicochemical property prediction, formulation prediction, absorption, distribution, metabolism, excretion and toxicity (ADME/Tox), target prediction and skin permeation, etc. We also show that there are many potential applications of deep learning beyond cheminformatics. It will be important to perform prospective testing (which has been carried out rarely to date) in order to convince skeptics that there will be benefits from investing in this technique.
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paper_title: Fast and Accurate Modeling of Molecular Atomization Energies with Machine Learning

paper_content:

We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schrödinger equation is mapped onto a nonlinear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross validation over more than seven thousand organic molecules yields a mean absolute error of ∼10 kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves.
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paper_title: Deep architectures for protein contact map prediction

paper_content:

Motivation: Residue–residue contact prediction is important for protein structure prediction and other applications. However, the accuracy of current contact predictors often barely exceeds 20% on long-range contacts, falling short of the level required for ab initio structure prediction. ::: ::: Results: Here, we develop a novel machine learning approach for contact map prediction using three steps of increasing resolution. First, we use 2D recursive neural networks to predict coarse contacts and orientations between secondary structure elements. Second, we use an energy-based method to align secondary structure elements and predict contact probabilities between residues in contacting alpha-helices or strands. Third, we use a deep neural network architecture to organize and progressively refine the prediction of contacts, integrating information over both space and time. We train the architecture on a large set of non-redundant proteins and test it on a large set of non-homologous domains, as well as on the set of protein domains used for contact prediction in the two most recent CASP8 and CASP9 experiments. For long-range contacts, the accuracy of the new CMAPpro predictor is close to 30%, a significant increase over existing approaches. ::: ::: Availability: CMAPpro is available as part of the SCRATCH suite at http://scratch.proteomics.ics.uci.edu/. ::: ::: Contact: pfbaldi@uci.edu ::: ::: Supplementary information:Supplementary data are available at Bioinformatics online.
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paper_title: HEALTHCARE PREDICTIVE MODELS BASED ON BIG DATA FUSION FROM BIOMEDICAL SENSORS

paper_content:

The paper presents a method for analyzing data from sensors and developing the predictive models based on learning methods. There are some methods, described on scientific literature, such as statistical methods (linear regression, logistic regression, and Bayesian models), advanced methods based on machine learning and data mining (decision trees and artificial neural networks) and survival models. All of these methods are intended to discover the correlation and covariance between biomedical parameters. ::: This paper presents the decision tree method for predictive health modeling based on machine learning and data mining. Based on this method used can be developed a decision support system for healthcare. Machine learning is used in healthcare predictive modeling for learning to recognize complex patterns within big data received from biomedical sensors. ::: The sensors data fusion refers to the usage of the sensors wireless network and data fusion on the same level (for similar sensors - e. g. temperature sensors) and on different levels (different sensors category - pulse, breath, temperature, moisture sensors) for developing the decision systems. ::: Big data concept is familiar for medical sciences (genomics, biomedical research) and also for physical sciences (meteorology, physics and chemistry), financial institutions (banking and capital markets) and government (defense). ::: For predictive models in clinical analysis is important to establish the time steps discretization of occurrence of a particular event (critical state required continuous monitoring) for observe the impact of the correlated values for biomedical parameters. These aspects presented are useful for healthcare learning about correlation between diseases and biomedical parameters.
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paper_title: Protein structure prediction from sequence variation

paper_content:

Genomic sequences contain rich evolutionary information about functional constraints on macromolecules such as proteins. This information can be efficiently mined to detect evolutionary couplings between residues in proteins and address the long-standing challenge to compute protein three-dimensional structures from amino acid sequences. Substantial progress has recently been made on this problem owing to the explosive growth in available sequences and the application of global statistical methods. In addition to three-dimensional structure, the improved understanding of covariation may help identify functional residues involved in ligand binding, protein-complex formation and conformational changes. We expect computation of covariation patterns to complement experimental structural biology in elucidating the full spectrum of protein structures, their functional interactions and evolutionary dynamics.
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paper_title: Big Data meets Quantum Chemistry Approximations: The $\Delta$-Machine Learning Approach

paper_content:

Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k constitutional isomers of C$_7$H$_{10}$O$_2$ we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semi-empirical quantum chemistry and machine learning models trained on 1 and 10\% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.
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paper_title: Deep Learning for Computational Chemistry

paper_content:

The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non-neural networks state-of-the-art models across disparate research topics, and deep neural network-based models often exceeded the “glass ceiling” expectations of their respective tasks. Coupled with the maturity of GPU-accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.
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paper_title: Discovery and Optimization of Materials Using Evolutionary Approaches

paper_content:

Materials science is undergoing a revolution, generating valuable new materials such as flexible solar panels, biomaterials and printable tissues, new catalysts, polymers, and porous materials with unprecedented properties. However, the number of potentially accessible materials is immense. Artificial evolutionary methods such as genetic algorithms, which explore large, complex search spaces very efficiently, can be applied to the identification and optimization of novel materials more rapidly than by physical experiments alone. Machine learning models can augment experimental measurements of materials fitness to accelerate identification of useful and novel materials in vast materials composition or property spaces. This review discusses the problems of large materials spaces, the types of evolutionary algorithms employed to identify or optimize materials, and how materials can be represented mathematically as genomes, describes fitness landscapes and mutation operators commonly employed in materials evo...
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paper_title: Computer-Assisted Synthetic Planning: The End of the Beginning

paper_content:

Exactly half a century has passed since the launch of the first documented research project (1965 Dendral) on computer-assisted organic synthesis. Many more programs were created in the 1970s and 1980s but the enthusiasm of these pioneering days had largely dissipated by the 2000s, and the challenge of teaching the computer how to plan organic syntheses earned itself the reputation of a "mission impossible". This is quite curious given that, in the meantime, computers have "learned" many other skills that had been considered exclusive domains of human intellect and creativity-for example, machines can nowadays play chess better than human world champions and they can compose classical music pleasant to the human ear. Although there have been no similar feats in organic synthesis, this Review argues that to concede defeat would be premature. Indeed, bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules (with full stereo- and regiochemistry) coded in appropriate formats, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes. The Review begins with an overview of some basic theoretical concepts essential for the big-data analysis of chemical syntheses. It progresses to the problem of optimizing pathways involving known reactions. It culminates with discussion of algorithms that allow for a completely de novo and fully automated design of syntheses leading to relatively complex targets, including those that have not been made before. Of course, there are still things to be improved, but computers are finally becoming relevant and helpful to the practice of organic-synthetic planning. Paraphrasing Churchill's famous words after the Allies' first major victory over the Axis forces in Africa, it is not the end, it is not even the beginning of the end, but it is the end of the beginning for the computer-assisted synthesis planning. The machine is here to stay.
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paper_title: Deep Learning for Computational Chemistry

paper_content:

The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non-neural networks state-of-the-art models across disparate research topics, and deep neural network-based models often exceeded the “glass ceiling” expectations of their respective tasks. Coupled with the maturity of GPU-accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.
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paper_title: Stalking the Materials Genome: A Data-Driven Approach to the Virtual Design of Nanostructured Polymers.

paper_content:

Accelerated insertion of nanocomposites into advanced applications is predicated on the ability to perform a priori property predictions on the resulting materials. In this paper, a paradigm for the virtual design of spherical nanoparticle-filled polymers is demonstrated. A key component of this "Materials Genomics" approach is the development and use of Materials Quantitative Structure-Property Relationship (MQSPR) models trained on atomic-level features of nanofiller and polymer constituents and used to predict the polar and dispersive components of their surface energies. Surface energy differences are then correlated with the nanofiller dispersion morphology and filler/matrix interface properties and integrated into a numerical analysis approach that allows the prediction of thermomechanical properties of the spherical nanofilled polymer composites. Systematic experimental studies of silica nanoparticles modified with three different surface chemistries in polystyrene (PS), poly(methyl methacrylate) (PMMA), poly(ethyl methacrylate) (PEMA) and poly(2-vinyl pyridine) (P2VP) are used to validate the models. While demonstrated here as effective for the prediction of meso-scale morphologies and macro-scale properties under quasi-equilibrium processing conditions, the protocol has far ranging implications for Virtual Design.
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paper_title: PubChemQC Project: A Large-Scale First-Principles Electronic Structure Database for Data-Driven Chemistry

paper_content:

Large-scale molecular databases play an essential role in the investigation of various subjects such as the development of organic materials, in silico drug design, and data-driven studies with machine learning. We have developed a large-scale quantum chemistry database based on first-principles methods. Our database currently contains the ground-state electronic structures of 3 million molecules based on density functional theory (DFT) at the B3LYP/6-31G* level, and we successively calculated 10 low-lying excited states of over 2 million molecules via time-dependent DFT with the B3LYP functional and the 6-31+G* basis set. To select the molecules calculated in our project, we referred to the PubChem Project, which was used as the source of the molecular structures in short strings using the InChI and SMILES representations. Accordingly, we have named our quantum chemistry database project “PubChemQC” (http://pubchemqc.riken.jp/) and placed it in the public domain. In this paper, we show the fundamental fe...
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paper_title: Discovering predictive rules of chemistry from property landscapes

paper_content:

Abstract Predicting the chemical and physical properties of molecules often relies on systematic rules relating the properties to molecular characteristics. This Letter introduces a novel method to reveal predictive chemical rules based on analysis of the chemical property landscape , which specifies the functional relationship between a measured property and an appropriate set of molecular variables. As an illustration, we consider landscapes relating the 17 O NMR chemical shift, 13 C NMR chemical shift, and IR vibrational frequency to the moieties attached to a carbonyl group. Implications of this ‘Chemscape’ formulation for general molecular property prediction are discussed.
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paper_title: Discovery and Optimization of Materials Using Evolutionary Approaches

paper_content:

Materials science is undergoing a revolution, generating valuable new materials such as flexible solar panels, biomaterials and printable tissues, new catalysts, polymers, and porous materials with unprecedented properties. However, the number of potentially accessible materials is immense. Artificial evolutionary methods such as genetic algorithms, which explore large, complex search spaces very efficiently, can be applied to the identification and optimization of novel materials more rapidly than by physical experiments alone. Machine learning models can augment experimental measurements of materials fitness to accelerate identification of useful and novel materials in vast materials composition or property spaces. This review discusses the problems of large materials spaces, the types of evolutionary algorithms employed to identify or optimize materials, and how materials can be represented mathematically as genomes, describes fitness landscapes and mutation operators commonly employed in materials evo...
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paper_title: Directed development of high-performance membranes via high-throughput and combinatorial strategies.

paper_content:

Combinatorial strategies are for the first time applied in membrane technology and prove to be a powerful new tool in the search for novel membrane materials. The selected system for this study is a polyimide solvent-resistant nanofiltration membrane prepared via phase inversion. The phase inversion process is a typical membrane synthesis procedure involving a large number of compositional components, which can each be varied in a wide concentration range. The optimization of the membrane dope composition was performed using evolutionary optimization via genetic algorithms. Compared with the best commercially available membranes, a substantially improved membrane performance could be realized, both on the level of membrane selectivity and on that of permeability. The miniaturized high-throughput synthesis procedure could be scaled up successfully when the polymer dope was sufficiently viscous. It can be anticipated that application of combinatorial techniques can potentially lead to major improvements in all fields of membrane technology, for example water treatment, gas separation, and dialysis, not only on the compositional level but also for instance on the level of membrane synthesis posttreatment and operational conditions.
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paper_title: Deep Learning for Computational Chemistry

paper_content:

The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non-neural networks state-of-the-art models across disparate research topics, and deep neural network-based models often exceeded the “glass ceiling” expectations of their respective tasks. Coupled with the maturity of GPU-accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.
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paper_title: Clinical chemistry in higher dimensions: Machine-learning and enhanced prediction from routine clinical chemistry data.

paper_content:

Big Data is having an impact on many areas of research, not the least of which is biomedical science. In this review paper, big data and machine learning are defined in terms accessible to the clinical chemistry community. Seven myths associated with machine learning and big data are then presented, with the aim of managing expectation of machine learning amongst clinical chemists. The myths are illustrated with four examples investigating the relationship between biomarkers in liver function tests, enhanced laboratory prediction of hepatitis virus infection, the relationship between bilirubin and white cell count, and the relationship between red cell distribution width and laboratory prediction of anaemia.
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paper_title: Expert system methodologies and applications—a decade review from 1995 to 2004

paper_content:

Abstract This paper surveys expert systems (ES) development using a literature review and classification of articles from 1995 to 2004 with a keyword index and article abstract in order to explore how ES methodologies and applications have developed during this period. Based on the scope of 166 articles from 78 academic journals (retrieved from five online database) of ES applications, this paper surveys and classifies ES methodologies using the following eleven categories: rule-based systems, knowledge-based systems, neural networks, fuzzy ESs, object-oriented methodology, case-based reasoning, system architecture, intelligent agent systems, database methodology, modeling, and ontology together with their applications for different research and problem domains. Discussion is presented, indicating the followings future development directions for ES methodologies and applications: (1) ES methodologies are tending to develop towards expertise orientation and ES applications development is a problem-oriented domain. (2) It is suggested that different social science methodologies, such as psychology, cognitive science, and human behavior could implement ES as another kind of methodology. (3) The ability to continually change and obtain new understanding is the driving power of ES methodologies, and should be the ES application of future works.
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paper_title: Neural‐Symbolic Machine Learning for Retrosynthesis and Reaction Prediction

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Reaction prediction and retrosynthesis are the cornerstones of organic chemistry. Rule-based expert systems have been the most widespread approach to computationally solve these two related challenges to date. However, reaction rules often fail because they ignore the molecular context, which leads to reactivity conflicts. Herein, we report that deep neural networks can learn to resolve reactivity conflicts and to prioritize the most suitable transformation rules. We show that by training our model on 3.5 million reactions taken from the collective published knowledge of the entire discipline of chemistry, our model exhibits a top10-accuracy of 95 % in retrosynthesis and 97 % for reaction prediction on a validation set of almost 1 million reactions.
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paper_title: Organic Chemistry as a Language and the Implications of Chemical Linguistics for Structural and Retrosynthetic Analyses

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Methods of computational linguistics are used to demonstrate that a natural language such as English and organic chemistry have the same structure in terms of the frequency of, respectively, text fragments and molecular fragments. This quantitative correspondence suggests that it is possible to extend the methods of computational corpus linguistics to the analysis of organic molecules. It is shown that within organic molecules bonds that have highest information content are the ones that 1) define repeat/symmetry subunits and 2) in asymmetric molecules, define the loci of potential retrosynthetic disconnections. Linguistics-based analysis appears well-suited to the analysis of complex structural and reactivity patterns within organic molecules.
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paper_title: Computer-Assisted Synthetic Planning: The End of the Beginning

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Exactly half a century has passed since the launch of the first documented research project (1965 Dendral) on computer-assisted organic synthesis. Many more programs were created in the 1970s and 1980s but the enthusiasm of these pioneering days had largely dissipated by the 2000s, and the challenge of teaching the computer how to plan organic syntheses earned itself the reputation of a "mission impossible". This is quite curious given that, in the meantime, computers have "learned" many other skills that had been considered exclusive domains of human intellect and creativity-for example, machines can nowadays play chess better than human world champions and they can compose classical music pleasant to the human ear. Although there have been no similar feats in organic synthesis, this Review argues that to concede defeat would be premature. Indeed, bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules (with full stereo- and regiochemistry) coded in appropriate formats, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes. The Review begins with an overview of some basic theoretical concepts essential for the big-data analysis of chemical syntheses. It progresses to the problem of optimizing pathways involving known reactions. It culminates with discussion of algorithms that allow for a completely de novo and fully automated design of syntheses leading to relatively complex targets, including those that have not been made before. Of course, there are still things to be improved, but computers are finally becoming relevant and helpful to the practice of organic-synthetic planning. Paraphrasing Churchill's famous words after the Allies' first major victory over the Axis forces in Africa, it is not the end, it is not even the beginning of the end, but it is the end of the beginning for the computer-assisted synthesis planning. The machine is here to stay.
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paper_title: “ Found in Translation ” : Predicting Outcomes of Complex Organic Chemistry Reactions using Neural Sequence-to-Sequence Models †

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There is an intuitive analogy of an organic chemist's understanding of a compound and a language speaker's understanding of a word. Consequently, it is possible to introduce the basic concepts and analyze potential impacts of linguistic analysis to the world of organic chemistry. In this work, we cast the reaction prediction task as a translation problem by introducing a template-free sequence-to-sequence model, trained end-to-end and fully data-driven. We propose a novel way of tokenization, which is arbitrarily extensible with reaction information. With this approach, we demonstrate results superior to the state-of-the-art solution by a significant margin on the top-1 accuracy. Specifically, our approach achieves an accuracy of 80.1% without relying on auxiliary knowledge such as reaction templates. Also, 66.4% accuracy is reached on a larger and noisier dataset.
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paper_title: Electronic Spectra from TDDFT and Machine Learning in Chemical Space

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Due to its favorable computational efficiency, time-dependent (TD) density functional theory (DFT) enables the prediction of electronic spectra in a high-throughput manner across chemical space. Its predictions, however, can be quite inaccurate. We resolve this issue with machine learning models trained on deviations of reference second-order approximate coupled-cluster (CC2) singles and doubles spectra from TDDFT counterparts, or even from DFT gap. We applied this approach to low-lying singlet-singlet vertical electronic spectra of over 20 000 synthetically feasible small organic molecules with up to eight CONF atoms. The prediction errors decay monotonously as a function of training set size. For a training set of 10 000 molecules, CC2 excitation energies can be reproduced to within ±0.1 eV for the remaining molecules. Analysis of our spectral database via chromophore counting suggests that even higher accuracies can be achieved. Based on the evidence collected, we discuss open challenges associated with data-driven modeling of high-lying spectra and transition intensities.
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paper_title: Modeling Electronic Quantum Transport with Machine Learning

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We present a machine learning approach to solve electronic quantum transport equations of one-dimensional nanostructures. The transmission coefficients of disordered systems were computed to provide training and test data sets to the machine. The system's representation encodes energetic as well as geometrical information to characterize similarities between disordered configurations, while the Euclidean norm is used as a measure of similarity. Errors for out-of-sample predictions systematically decrease with training set size, enabling the accurate and fast prediction of new transmission coefficients. The remarkable performance of our model to capture the complexity of interference phenomena lends further support to its viability in dealing with transport problems of undulatory nature.
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paper_title: Extracting Crystal Chemistry from Amorphous Carbon Structures

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Carbon allotropes have been explored intensively by ab initio crystal structure prediction, but such methods are limited by the large computational cost of the underlying density functional theory (DFT). Here we show that a novel class of machine-learning-based interatomic potentials can be used for random structure searching and readily predicts several hitherto unknown carbon allotropes. Remarkably, our model draws structural information from liquid and amorphous carbon exclusively, and so does not have any prior knowledge of crystalline phases: it therefore demonstrates true transferability, which is a crucial prerequisite for applications in chemistry. The method is orders of magnitude faster than DFT and can, in principle, be coupled with any algorithm for structure prediction. Machine-learning models therefore seem promising to enable large-scale structure searches in the future.
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paper_title: Big Data meets Quantum Chemistry Approximations: The $\Delta$-Machine Learning Approach

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Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k constitutional isomers of C$_7$H$_{10}$O$_2$ we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semi-empirical quantum chemistry and machine learning models trained on 1 and 10\% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.
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paper_title: Structure-based Sampling and Self-correcting Machine Learning for Accurate Calculations of Potential Energy Surfaces and Vibrational Levels

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We present an efficient approach for generating highly accurate molecular potential energy surfaces (PESs) using self-correcting, kernel ridge regression (KRR) based machine learning (ML). We introduce structure-based sampling to automatically assign nuclear configurations from a pre-defined grid to the training and prediction sets, respectively. Accurate high-level ab initio energies are required only for the points in the training set, while the energies for the remaining points are provided by the ML model with negligible computational cost. The proposed sampling procedure is shown to be superior to random sampling and also eliminates the need for training several ML models. Self-correcting machine learning has been implemented such that each additional layer corrects errors from the previous layer. The performance of our approach is demonstrated in a case study on a published high-level ab initio PES of methyl chloride with 44 819 points. The ML model is trained on sets of different sizes and then used to predict the energies for tens of thousands of nuclear configurations within seconds. The resulting datasets are utilized in variational calculations of the vibrational energy levels of CH3Cl. By using both structure-based sampling and self-correction, the size of the training set can be kept small (e.g., 10% of the points) without any significant loss of accuracy. In ab initio rovibrational spectroscopy, it is thus possible to reduce the number of computationally costly electronic structure calculations through structure-based sampling and self-correcting KRR-based machine learning by up to 90%.
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paper_title: Site of Metabolism Prediction Based on ab initio Derived Atom Representations

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Machine learning models for site of metabolism (SoM) prediction offer the ability to identify metabolic soft spots in low-molecular-weight drug molecules at low computational cost and enable data-based reactivity prediction. SoM prediction is an atom classification problem. Successful construction of machine learning models requires atom representations that capture the reactivity-determining features of a potential reaction site. We have developed a descriptor scheme that characterizes an atom's steric and electronic environment and its relative location in the molecular structure. The partial charge distributions were obtained from fast quantum mechanical calculations. We successfully trained machine learning classifiers on curated cytochrome P450 metabolism data. The models based on the new atom descriptors showed sustained accuracy for retrospective analyses of metabolism optimization campaigns and lead optimization projects from Bayer Pharmaceuticals. The results obtained demonstrate the practicality of quantum-chemistry-supported machine learning models for hit-to-lead optimization.
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paper_title: A Novel Approach for Predicting P-glycoprotein (ABCB1) Inhibition Using Molecular Interaction Fields

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P-glycoprotein (Pgp or ABCB1) is an ABC transporter protein involved in intestinal absorption, drug metabolism, and brain penetration, and its inhibition can seriously alter a drug's bioavailability and safety. In addition, inhibitors of Pgp can be used to overcome multidrug resistance. Given this dual purpose, reliable in silico procedures to predict Pgp inhibition are of great interest. A large and accurate literature collection yielded more than 1200 structures; a model was then constructed using various molecular interaction field-based technologies, considering pharmacophoric features and those physicochemical properties related to membrane partitioning. High accuracy was demonstrated internally with two different validation sets and, moreover, using a number of molecules, for which Pgp inhibition was not experimentally available but was evaluated in-house. All of the validations confirmed the robustness of the model and its suitability to help medicinal chemists in drug discovery. The information de...
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paper_title: Classification of Cytochrome P450 Inhibitors and Noninhibitors Using Combined Classifiers

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Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP) inhibition is an important consideration, especially, during the research phase of drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP isoform. In this study, inhibitor predicting models were developed for five major CYP isoforms, namely 1A2, 2C9, 2C19, 2D6, and 3A4, using a combined classifier algorithm on a large data set containing more than 24,700 unique compounds, extracted from PubChem. The combined classifiers algorithm is an ensemble of different independent machine learning classifiers including support vector machine, C4.5 decision tree, k-nearest neighbor, and naïve Bayes, fused by a back-propagation artificial neural network (BP-ANN). All developed models were validated by 5-fold cross-validation and a diverse validation set composed of about 9000 diverse unique compounds. The range of the area under the receiver operating characteristic curve (AUC) for the validation sets was 0.764 to 0.815 for CYP1A2, 0.837 to 0.861 for CYP2C9, 0.793 to 0.842 for CYP2C19, 0.839 to 0.886 for CYP2D6, and 0.754 to 0.790 for CYP3A4, respectively, using the new developed combined classifiers. The overall performance of the combined classifiers fused by BP-ANN was superior to that of three classic fusion techniques (Mean, Maximum, and Multiply). The chemical spaces of data sets were explored by multidimensional scaling plots, and the use of applicability domain improved the prediction accuracies of models. In addition, some representative substructure fragments differentiating CYP inhibitors and noninhibitors were characterized by the substructure fragment analysis. These classification models are applicable for virtual screening of the five major CYP isoforms inhibitors or can be used as simple filters of potential chemicals in drug discovery.
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paper_title: In silico prediction of Tetrahymena pyriformis toxicity for diverse industrial chemicals with substructure pattern recognition and machine learning methods

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There is an increasing need for the rapid safety assessment of chemicals by both industries and regulatory agencies throughout the world. In silico techniques are practical alternatives in the environmental hazard assessment. It is especially true to address the persistence, bioaccumulative and toxicity potentials of organic chemicals. Tetrahymena pyriformis toxicity is often used as a toxic endpoint. In this study, 1571 diverse unique chemicals were collected from the literature and composed of the largest diverse data set for T. pyriformis toxicity. Classification predictive models of T. pyriformis toxicity were developed by substructure pattern recognition and different machine learning methods, including support vector machine (SVM), C4.5 decision tree, k-nearest neighbors and random forest. The results of a 5-fold cross-validation showed that the SVM method performed better than other algorithms. The overall predictive accuracies of the SVM classification model with radial basis functions kernel was 92.2% for the 5-fold cross-validation and 92.6% for the external validation set, respectively. Furthermore, several representative substructure patterns for characterizing T. pyriformis toxicity were also identified via the information gain analysis methods.
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paper_title: Insights into Molecular Basis of Cytochrome P450 Inhibitory Promiscuity of Compounds

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Cytochrome P450 inhibitory promiscuity of a drug has potential effects on the occurrence of clinical drug-drug interactions. Understanding how a molecular property is related to the P450 inhibitory promiscuity could help to avoid such adverse effects. In this study, an entropy-based index was defined to quantify the P450 inhibitory promiscuity of a compound based on a comprehensive data set, containing more than 11,500 drug-like compounds with inhibition against five major P450 isoforms, 1A2, 2C9, 2C19, 2D6, and 3A4. The results indicated that the P450 inhibitory promiscuity of a compound would have a moderate correlation with molecular aromaticity, a minor correlation with molecular lipophilicity, and no relations with molecular complexity, hydrogen bonding ability, and TopoPSA. We also applied an index to quantify the susceptibilities of different P450 isoforms to inhibition based on the same data set. The results showed that there was a surprising level of P450 inhibitory promiscuity even for substrate specific P450, susceptibility to inhibition follows the rank-order: 1A2 > 2C19 > 3A4 > 2C9 > 2D6. There was essentially no correlation between P450 inhibitory potency and specificity and minor negative trade-offs between P450 inhibitory promiscuity and catalytic promiscuity. In addition, classification models were built to predict the P450 inhibitory promiscuity of new chemicals using support vector machine algorithm with different fingerprints. The area under the receiver operating characteristic curve of the best model was about 0.9, evaluated by 5-fold cross-validation. These findings would be helpful for understanding the mechanism of P450 inhibitory promiscuity and improving the P450 inhibitory selectivity of new chemicals in drug discovery.
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paper_title: Estimation of ADME Properties with Substructure Pattern Recognition

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Over the past decade, absorption, distribution, metabolism, and excretion (ADME) property evaluation has become one of the most important issues in the process of drug discovery and development. Since in vivo and in vitro evaluations are costly and laborious, in silico techniques had been widely used to estimate ADME properties of chemical compounds. Traditional prediction methods usually try to build a functional relationship between a set of molecular descriptors and a given ADME property. Although traditional methods have been successfully used in many cases, the accuracy and efficiency of molecular descriptors must be concerned. Herein, we report a new classification method based on substructure pattern recognition, in which each molecule is represented as a substructure pattern fingerprint based on a predefined substructure dictionary, and then a support vector machine (SVM) algorithm is applied to build the prediction model. Therefore, a direct connection between substructures and molecular properti...
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paper_title: Enriching Complex Networks with Word Embeddings for Detecting Mild Cognitive Impairment from Speech Transcripts

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Mild Cognitive Impairment (MCI) is a mental disorder difficult to diagnose. Linguistic features, mainly from parsers, have been used to detect MCI, but this is not suitable for large-scale assessments. MCI disfluencies produce non-grammatical speech that requires manual or high precision automatic correction of transcripts. In this paper, we modeled transcripts into complex networks and enriched them with word embedding (CNE) to better represent short texts produced in neuropsychological assessments. The network measurements were applied with well-known classifiers to automatically identify MCI in transcripts, in a binary classification task. A comparison was made with the performance of traditional approaches using Bag of Words (BoW) and linguistic features for three datasets: DementiaBank in English, and Cinderella and Arizona-Battery in Portuguese. Overall, CNE provided higher accuracy than using only complex networks, while Support Vector Machine was superior to other classifiers. CNE provided the highest accuracies for DementiaBank and Cinderella, but BoW was more efficient for the Arizona-Battery dataset probably owing to its short narratives. The approach using linguistic features yielded higher accuracy if the transcriptions of the Cinderella dataset were manually revised. Taken together, the results indicate that complex networks enriched with embedding is promising for detecting MCI in large-scale assessments
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paper_title: admetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET Properties

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Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/development of drugs, pesticides, food additives, consumer products, and industrial chemicals. This information is especially useful when to conduct environmental and human hazard assessment. The most critical rate limiting step in the chemical safety assessment workflow is the availability of high quality data. This paper describes an ADMET structure–activity relationship database, abbreviated as admetSAR. It is an open source, text and structure searchable, and continually updated database that collects, curates, and manages available ADMET-associated properties data from the published literature. In admetSAR, over 210 000 ADMET annotated data points for more than 96 000 unique compounds with 45 kinds of ADMET-associated properties, proteins, species, or organisms have been carefully curated from a large number of diverse literatures. The database provides a user-friendly interface to query a...
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paper_title: Learning from the Harvard Clean Energy Project: The Use of Neural Networks to Accelerate Materials Discovery

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Here, the employment of multilayer perceptrons, a type of artificial neural network, is proposed as part of a computational funneling procedure for high-throughput organic materials design. Through the use of state of the art algorithms and a large amount of data extracted from the Harvard Clean Energy Project, it is demonstrated that these methods allow a great reduction in the fraction of the screening library that is actually calculated. Neural networks can reproduce the results of quantum-chemical calculations with a large level of accuracy. The proposed approach allows to carry out large-scale molecular screening projects with less computational time. This, in turn, allows for the exploration of increasingly large and diverse libraries.
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paper_title: 3D-QSAR in drug design--a review.

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Quantitative structure-activity relationships (QSAR) have been applied for decades in the development of relationships between physicochemical properties of chemical substances and their biological activities to obtain a reliable statistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the formalism is that the difference in structural properties is responsible for the variations in biological activities of the compounds. In the classical QSAR studies, affinities of ligands to their binding sites, inhibition constants, rate constants, and other biological end points, with atomic, group or molecular properties such as lipophilicity, polarizability, electronic and steric properties (Hansch analysis) or with certain structural features (Free-Wilson analysis) have been correlated. However such an approach has only a limited utility for designing a new molecule due to the lack of consideration of the 3D structure of the molecules. 3D-QSAR has emerged as a natural extension to the classical Hansch and Free-Wilson approaches, which exploits the three-dimensional properties of the ligands to predict their biological activities using robust chemometric techniques such as PLS, G/PLS, ANN etc. It has served as a valuable predictive tool in the design of pharmaceuticals and agrochemicals. Although the trial and error factor involved in the development of a new drug cannot be ignored completely, QSAR certainly decreases the number of compounds to be synthesized by facilitating the selection of the most promising candidates. Several success stories of QSAR have attracted the medicinal chemists to investigate the relationships of structural properties with biological activity. This review seeks to provide a bird's eye view of the different 3D-QSAR approaches employed within the current drug discovery community to construct predictive structure-activity relationships and also discusses the limitations that are fundamental to these approaches, as well as those that might be overcome with the improved strategies. The components involved in building a useful 3D-QSAR model are discussed, including the validation techniques available for this purpose.
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paper_title: DRAGON SOFTWARE: AN EASY APPROACH TO MOLECULAR DESCRIPTOR CALCULATIONS

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Due to the relevance that molecular descriptors are constantly gaining in several scientific fields, software for the calculation of molecular descriptors have become very important tools for the scientists. In this paper, the main characteristics of DRAGON software for the calculation of molecular descriptors are shortly illustrated.
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paper_title: Principles of QSAR models validation: internal and external

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The recent REACH Policy of the European Union has led to scientists and regulators to focus their attention on establishing general validation principles for QSAR models in the context of chemical regulation (previously known as the Setubal, nowadays, the OECD principles). This paper gives a brief analysis of some principles: unambiguous algorithm, Applicability Domain (AD), and statistical validation. Some concerns related to QSAR algorithm reproducibility and an example of a fast check of the applicability domain for MLR models are presented. Common myths and misconceptions related to popular techniques for verifying internal predictivity, particularly for MLR models (for instance crossvalidation, bootstrap), are commented on and compared with commonly used statistical techniques for external validation. The differences in the two validating approaches are highlighted, and evidence is presented that only models that have been validated externally, after their internal validation, can be considered reliable and applicable for both external prediction and regulatory purposes. (“Validation is one of those words...that is constantly used and seldom defined” as stated by A. R. Feinstein in the book Multivariate Analysis: An Introduction, Yale University Press, New Haven, 1996).
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paper_title: Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB).

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Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project.
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paper_title: Macromolecular target prediction by self-organizing feature maps.

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INTRODUCTION ::: Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.
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paper_title: Sparse Neural Network Models of Antimicrobial Peptide-Activity Relationships.

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We present an adaptive neural network model for chemical data classification. The method uses an evolutionary algorithm for optimizing the network structure by seeking sparsely connected architectures. The number of hidden layers, the number of neurons in each layer and their connectivity are free variables of the system. We used the method for predicting antimicrobial peptide activity from the amino acid sequence. Visualization of the evolved sparse network structures suggested a high charge density and a low aggregation potential in solution as beneficial for antimicrobial activity. However, different training data sets and peptide representations resulted in greatly varying network structures. Overall, the sparse network models turned out to be less accurate than fully-connected networks. In a prospective application, we synthesized and tested 10 de novo generated peptides that were predicted to either possess antimicrobial activity, or to be inactive. Two of the predicted antibacterial peptides showed cosiderable bacteriostatic effects against both Staphylococcus aureus and Escherichia coli. None of the predicted inactive peptides possessed antibacterial properties. Molecular dynamics simulations of selected peptide structures in water and TFE suggest a pronounced peptide helicity in a hydrophobic environment. The results of this study underscore the applicability of neural networks for guiding the computer-assisted design of new peptides with desired properties.
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paper_title: Antimicrobial activity predictors benchmarking analysis using shuffled and designed synthetic peptides.

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The antimicrobial activity prediction tools aim to help the novel antimicrobial peptides (AMP) sequences discovery, utilizing machine learning methods. Such approaches have gained increasing importance in the generation of novel synthetic peptides by means of rational design techniques. This study focused on predictive ability of such approaches to determine the antimicrobial sequence activities, which were previously characterized at the protein level by in vitro studies. Using four web servers and one standalone software, we evaluated 78 sequences generated by the so-called linguistic model, being 40 designed and 38 shuffled sequences, with ∼60 and ∼25% of identity to AMPs, respectively. The ab initio molecular modelling of such sequences indicated that the structure does not affect the predictions, as both sets present similar structures. Overall, the systems failed on predicting shuffled versions of designed peptides, as they are identical in AMPs composition, which implies in accuracies below 30%. The prediction accuracy is negatively affected by the low specificity of all systems here evaluated, as they, on the other hand, reached 100% of sensitivity. Our results suggest that complementary approaches with high specificity, not necessarily high accuracy, should be developed to be used together with the current systems, overcoming their limitations.
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paper_title: Quantum-Chemical Descriptors in QSAR/QSPR Studies

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Quantitative structure-activity and structureproperty relationship (QSAR/QSPR) studies are unquestionably of great importance in modern chemistry and biochemistry. The concept of QSAR/QSPR is to transform searches for compounds with desired properties using chemical intuition and experience into a mathematically quantified and computerized form. Once a correlation between structure and activity/property is found, any number of compounds, including those not yet synthesized, can be readily screened on the computer in order to select structures with the properties desired. It is then possible to select the most promising compounds to synthesize and test in the laboratory. Thus, the QSAR/QSPR approach conserves resources and accelerates the process of development of new molecules for use as drugs, materials, additives, or for any other purpose. While it is not easy to find successful structureactivity/property correlations, the recent exponential growth in the number of papers dealing with QSAR/ QSPR studies clearly demonstrates the rapid progress in this area. To obtain a significant correlation, it is crucial that appropriate descriptors be employed, whether they are theoretical, empirical, or derived from readily available experimental characteristics of the structures. Many descriptors reflect simple molecular properties and thus can provide insight into the physicochemical nature of the activity/ property under consideration. Recent progress in computational hardware and the development of efficient algorithms has assisted the routine development of molecular quantummechanical calculations. New semiempirical methods supply realistic quantum-chemical molecular quantities in a relatively short computational time frame. Quantum chemical calculations are thus an attractive source of new molecular descriptors, which can, in principle, express all of the electronic and geometric properties of molecules and their interactions. Indeed, many recent QSAR/QSPR studies have employed quantum chemical descriptors alone or in combination with conventional descriptors. Quantum chemistry provides a more accurate and detailed description of electronic effects than empirical methods.1 Quantum chemical methods can be applied to quantitative structure-activity relationships by direct derivation of electronic descriptors from the molecular wave function. In many cases it has been established that errors due to the approximate nature of quantum-chemical methods and the neglect of the solvation effects are largely transferable within structurally related series; thus, relative values of calculated descriptors can be meaningful even though their absolute values are not directly applicable.2 Moreover, electronic descriptors derived from the molecular wave function can be also partitioned on the basis of atoms or groups, allowing the description of various molecular regions separately. Most work employing quantum chemical descriptors has been carried out in the field of QSAR rather than QSPR, i.e. the descriptors have been correlated with biological activities such as enzyme inhibition activity, hallucinogenic activity, etc.3-6 In part this has been because, historically, the search for quantitative relationships with chemical structure started with the development of theoretical drug design methods. Quantum-chemical descriptors have also been reported to correlate the reactivity of organic compounds, octanol/water partition coefficients, chromatographic retention indices, and various physical properties of molecules.7-11 The present article reviews applications of quantum chemical descriptors in the development of QSAR/QSPR dealing with the chemical, physical, biochemical, and pharmacological properties of compounds.
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paper_title: Using random forest and decision tree models for a new vehicle prediction approach in computational toxicology

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Drug vehicles are chemical carriers that provide beneficial aid to the drugs they bear. Taking advantage of their favourable properties can potentially allow the safer use of drugs that are considered highly toxic. A means for vehicle selection without experimental trial would therefore be of benefit in saving time and money for the industry. Although machine learning is increasingly used in predictive toxicology, to our knowledge there is no reported work in using machine learning techniques to model drug-vehicle relationships for vehicle selection to minimise toxicity. In this paper we demonstrate the use of data mining and machine learning techniques to process, extract and build models based on classifiers (decision trees and random forests) that allow us to predict which vehicle would be most suited to reduce a drug's toxicity. Using data acquired from the National Institute of Health's (NIH) Developmental Therapeutics Program (DTP) we propose a methodology using an area under a curve (AUC) approach that allows us to distinguish which vehicle provides the best toxicity profile for a drug and build classification models based on this knowledge. Our results show that we can achieve prediction accuracies of 80 % using random forest models whilst the decision tree models produce accuracies in the 70 % region. We consider our methodology widely applicable within the scientific domain and beyond for comprehensively building classification models for the comparison of functional relationships between two variables.
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paper_title: AtomNet: A Deep Convolutional Neural Network for Bioactivity Prediction in Structure-based Drug Discovery

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Deep convolutional neural networks comprise a subclass of deep neural networks (DNN) with a constrained architecture that leverages the spatial and temporal structure of the domain they model. Convolutional networks achieve the best predictive performance in areas such as speech and image recognition by hierarchically composing simple local features into complex models. Although DNNs have been used in drug discovery for QSAR and ligand-based bioactivity predictions, none of these models have benefited from this powerful convolutional architecture. This paper introduces AtomNet, the first structure-based, deep convolutional neural network designed to predict the bioactivity of small molecules for drug discovery applications. We demonstrate how to apply the convolutional concepts of feature locality and hierarchical composition to the modeling of bioactivity and chemical interactions. In further contrast to existing DNN techniques, we show that AtomNet's application of local convolutional filters to structural target information successfully predicts new active molecules for targets with no previously known modulators. Finally, we show that AtomNet outperforms previous docking approaches on a diverse set of benchmarks by a large margin, achieving an AUC greater than 0.9 on 57.8% of the targets in the DUDE benchmark.
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paper_title: Deep Learning in Drug Discovery

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Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks.
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paper_title: Best Practices for QSAR Model Development, Validation, and Exploitation.

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After nearly five decades "in the making", QSAR modeling has established itself as one of the major computational molecular modeling methodologies. As any mature research discipline, QSAR modeling can be characterized by a collection of well defined protocols and procedures that enable the expert application of the method for exploring and exploiting ever growing collections of biologically active chemical compounds. This review examines most critical QSAR modeling routines that we regard as best practices in the field. We discuss these procedures in the context of integrative predictive QSAR modeling workflow that is focused on achieving models of the highest statistical rigor and external predictive power. Specific elements of the workflow consist of data preparation including chemical structure (and when possible, associated biological data) curation, outlier detection, dataset balancing, and model validation. We especially emphasize procedures used to validate models, both internally and externally, as well as the need to define model applicability domains that should be used when models are employed for the prediction of external compounds or compound libraries. Finally, we present several examples of successful applications of QSAR models for virtual screening to identify experimentally confirmed hits.
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paper_title: Deep Learning for Drug-Induced Liver Injury

paper_content:

Drug-induced liver injury (DILI) has been the single most frequent cause of safety-related drug marketing withdrawals for the past 50 years. Recently, deep learning (DL) has been successfully applied in many fields due to its exceptional and automatic learning ability. In this study, DILI prediction models were developed using DL architectures, and the best model trained on 475 drugs predicted an external validation set of 198 drugs with an accuracy of 86.9%, sensitivity of 82.5%, specificity of 92.9%, and area under the curve of 0.955, which is better than the performance of previously described DILI prediction models. Furthermore, with deep analysis, we also identified important molecular features that are related to DILI. Such DL models could improve the prediction of DILI risk in humans. The DL DILI prediction models are freely available at http://www.repharma.cn/DILIserver/DILI_home.php.
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paper_title: Low-dimensional carbon based sensors and sensing network for wearable health and environmental monitoring

paper_content:

With the advent of the era of big data and Internet of Things, wearable electronics are becoming more imperative than ever before, which prompts the continuous and fruitful research on wearable sensors and sensing network for health and environmental monitoring. This article presents an in-depth overview and review of this fertile area, focusing on sensors and sensing networks for strain, pressure, surface bio-potential, gas and temperature, which are made from low-dimensional carbon nano-materials and their composites. It covers materials, device structures, fabrication, performance and applications. It’s evident that the appropriate and deliberate selection of low-dimensional carbon materials, matrix and substrate materials, and their interactions, as well as effective structural designs, are essential for highly sensitive and stable performance. Finally, the current status of industrial application is presented, possible hindrances for the adaptation of the technology are discussed, and future directions of development are indicated.
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paper_title: Information Visualization and Feature Selection Methods Applied to Detect Gliadin in Gluten-Containing Foodstuff with a Microfluidic Electronic Tongue

paper_content:

The fast growth of celiac disease diagnosis has sparked the production of gluten-free food and the search for reliable methods to detect gluten in foodstuff. In this paper, we report on a microfluidic electronic tongue (e-tongue) capable of detecting trace amounts of gliadin, a protein of gluten, down to 0.005 mg kg–1 in ethanol solutions, and distinguishing between gluten-free and gluten-containing foodstuff. In some cases, it is even possible to determine whether gluten-free foodstuff has been contaminated with gliadin. That was made possible with an e-tongue comprising four sensing units, three of which made of layer-by-layer (LbL) films of semiconducting polymers deposited onto gold interdigitated electrodes placed inside microchannels. Impedance spectroscopy was employed as the principle of detection, and the electrical capacitance data collected with the e-tongue were treated with information visualization techniques with feature selection for optimizing performance. The sensing units are disposable...
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paper_title: HEALTHCARE PREDICTIVE MODELS BASED ON BIG DATA FUSION FROM BIOMEDICAL SENSORS

paper_content:

The paper presents a method for analyzing data from sensors and developing the predictive models based on learning methods. There are some methods, described on scientific literature, such as statistical methods (linear regression, logistic regression, and Bayesian models), advanced methods based on machine learning and data mining (decision trees and artificial neural networks) and survival models. All of these methods are intended to discover the correlation and covariance between biomedical parameters. ::: This paper presents the decision tree method for predictive health modeling based on machine learning and data mining. Based on this method used can be developed a decision support system for healthcare. Machine learning is used in healthcare predictive modeling for learning to recognize complex patterns within big data received from biomedical sensors. ::: The sensors data fusion refers to the usage of the sensors wireless network and data fusion on the same level (for similar sensors - e. g. temperature sensors) and on different levels (different sensors category - pulse, breath, temperature, moisture sensors) for developing the decision systems. ::: Big data concept is familiar for medical sciences (genomics, biomedical research) and also for physical sciences (meteorology, physics and chemistry), financial institutions (banking and capital markets) and government (defense). ::: For predictive models in clinical analysis is important to establish the time steps discretization of occurrence of a particular event (critical state required continuous monitoring) for observe the impact of the correlated values for biomedical parameters. These aspects presented are useful for healthcare learning about correlation between diseases and biomedical parameters.
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paper_title: Detection of glucose and triglycerides using information visualization methods to process impedance spectroscopy data

paper_content:

Abstract In this paper we discuss the detection of glucose and triglycerides using information visualization methods to process impedance spectroscopy data. The sensing units contained either lipase or glucose oxidase immobilized in layer-by-layer (LbL) films deposited onto interdigitated electrodes. The optimization consisted in identifying which part of the electrical response and combination of sensing units yielded the best distinguishing ability. It is shown that complete separation can be obtained for a range of concentrations of glucose and triglyceride when the interactive document map (IDMAP) technique is used to project the data into a two-dimensional plot. Most importantly, the optimization procedure can be extended to other types of biosensors, thus increasing the versatility of analysis provided by tailored molecular architectures exploited with various detection principles.
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paper_title: Random subspace method for analysing coffee with electronic tongue

paper_content:

Electronic tongue (ET) systems based on nanostructured films and impedance spectroscopy have been successful in detecting trace amounts of impurities in water and distinguishing similar complex liquids, such as different wines and coffees. There is now the challenge to correlate the electrical response from an ET to taste as assessed by human experts. Employed is a hybrid regression approach based on the random subspace method and principal components analysis to predict the global quality of coffees. A high correlation between predicted scores and those assigned by expert tasters was obtained, which is represented by a Pearson coefficient of 0.964.
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paper_title: Carbon Nanotube Matrix for Highly Sensitive Biosensors To Detect Pancreatic Cancer Biomarker CA19-9

paper_content:

Biosensors fabricated with nanomaterials promise faster, cheaper, and more efficient alternatives to traditional, often bulky devices for early cancer diagnosis. In this study, we fabricated a thin film sensing unit on interdigitated gold electrodes combining polyethyleneimine and carbon nanotubes in a layer by layer fashion, onto which antibodies anti-CA19-9 were adsorbed with a supporting layer of N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide solution. By use of impedance spectroscopy, the pancreatic cancer biomarker CA19-9 was detected in a buffer with limit of detection of 0.35 U/mL. This high sensitivity allowed for distinction between samples of blood serum from patients with distinct probabilities to develop pancreatic cancer. The selectivity of the biosensor was confirmed in subsidiary experiments with HT-29 and SW-620 cell lines and possible interferents, e.g., p53 protein, ascorbic acid, and glucose, where significant changes in capacitance could only be measured with HT...
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paper_title: Nanomaterials for Diagnosis: Challenges and Applications in Smart Devices Based on Molecular Recognition

paper_content:

Clinical diagnosis has always been dependent on the efficient immobilization of biomolecules in solid matrices with preserved activity, but significant developments have taken place in recent years with the increasing control of molecular architecture in organized films. Of particular importance is the synergy achieved with distinct materials such as nanoparticles, antibodies, enzymes, and other nanostructures, forming structures organized on the nanoscale. In this review, emphasis will be placed on nanomaterials for biosensing based on molecular recognition, where the recognition element may be an enzyme, DNA, RNA, catalytic antibody, aptamer, and labeled biomolecule. All of these elements may be assembled in nanostructured films, whose layer-by-layer nature is essential for combining different properties in the same device. Sensing can be done with a number of optical, electrical, and electrochemical methods, which may also rely on nanostructures for enhanced performance, as is the case of reporting nan...
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paper_title: Discrimination of Brazilian propolis according to the seasoning using chemometrics and machine learning based on UV-Vis scanning data

paper_content:

Summary Propolis is a chemically complex biomass produced by honeybees (Apis mellifera) from plant resins added of salivary enzymes, beeswax, and pollen. The biological activities described for propolis were also identified for donor plant’s resin, but a big challenge for the standardization of the chemical composition and biological effects of propolis remains on a better understanding of the influence of seasonality on the chemical constituents of that raw material. Since propolis quality depends, among other variables, on the local flora which is strongly influenced by (a)biotic factors over the seasons, to unravel the harvest season effect on the propolis chemical profile is an issue of recognized importance. For that, fast, cheap, and robust analytical techniques seem to be the best choice for large scale quality control processes in the most demanding markets, e.g., human health applications. For that, UV-Visible (UV-Vis) scanning spectrophotometry of hydroalcoholic extracts (HE) of seventy-three propolis samples, collected over the seasons in 2014 (summer, spring, autumn, and winter) and 2015 (summer and autumn) in Southern Brazil was adopted. Further machine learning and chemometrics techniques were applied to the UV-Vis dataset aiming to gain insights as to the seasonality effect on the claimed chemical heterogeneity of propolis samples determined by changes in the flora of the geographic region under study. Descriptive and classification models were built following a chemometric approach, i.e. principal component analysis (PCA) and hierarchical clustering analysis (HCA) supported by scripts written in the R language. The UV-Vis profiles associated with chemometric analysis allowed identifying a typical pattern in propolis samples collected in the summer. Importantly, the discrimination based on PCA could be improved by using the dataset of the fingerprint region of phenolic compounds ( λ= 280-400 ηm), suggesting that besides the biological activities of those secondary metabolites, they also play a relevant role for the discrimination and classification of that complex matrix through bioinformatics tools. Finally, a series of machine learning approaches, e.g., partial least square-discriminant analysis (PLS-DA), k-Nearest Neighbors (kNN), and Decision Trees showed to be complementary to PCA and HCA, allowing to obtain relevant information as to the sample discrimination.
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paper_title: Efficient android electronic nose design for recognition and perception of fruit odors using Kernel Extreme Learning Machines

paper_content:

Abstract This study presents a novel android electronic nose construction using Kernel Extreme Learning Machines (KELMs). The construction consists of two parts. In the first part, an android electronic nose with fast and accurate detection and low cost are designed using Metal Oxide Semiconductor (MOS) gas sensors. In the second part, the KELMs are implemented to get the electronic nose to achieve fast and high accuracy recognition. The proposed algorithm is designed to recognize the odor of six fruits. Fruits at two concentration levels are placed to the sample chamber of the electronic nose to ensure the features invariant with the concentration. Odor samples in the form of time series are collected and preprocessed. This is a newly introduced simple feature extraction step that does not use any dimension reduction method. The obtained salient features are imported to the inputs of the KELMs. Additionally, K-Nearest Neighbor (K-NN) classifiers, the Support Vector Machines (SVMs), Least-Squares Support Vector Machines (LSSVMs), and Extreme Learning Machines (ELMs) are used for comparison. According to the comparative results for the proposed experimental setup, the KELMs produced good odor recognition performance in terms of the high test accuracy and fast response. In addition, odor concentration level was visualized on an android platform.
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paper_title: Odor Recognition in Multiple E-Nose Systems With Cross-Domain Discriminative Subspace Learning

paper_content:

In this paper, we propose an odor recognition framework for multiple electronic noses (E-noses), machine olfaction odor perception systems. Straight to the point, the proposed transferring odor recognition model is called cross-domain discriminative subspace learning (CDSL). General odor recognition problems with E-nose are single domain oriented, that is, recognition algorithms are often modeled and tested on the same one domain data set (i.e., from only one E-nose system). Different from that, we focus on a more realistic scenario: the recognition model is trained on a prepared source domain data set from a master E-nose system ${A}$ , but tested on another target domain data set from a slave system ${B}$ or ${C}$ with the same type of the master system ${A}$ . The internal device parameter variance between master and slave systems often results in data distribution discrepancy between source domain and target domain, such that single-domain-based odor recognition model may not be adapted to another domain. Therefore, we propose domain-adaptation-based odor recognition for addressing the realistic recognition scenario across systems. Specifically, the proposed CDSL method consists of three merits: 1) an intraclass scatter minimization- and an interclass scatter maximization-based discriminative subspace learning is solved on source domain; 2) a data fidelity and preservation constraint of the subspace is imposed on target domain without distortion; and 3) a minipatch feature weighted domain distance is minimized for closely connecting the source and target domains. Experiments and comparisons on odor recognition tasks in multiple E-noses demonstrate the efficiency of the proposed method.
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paper_title: Wearable Chemical Sensors: Present Challenges and Future Prospects

paper_content:

Wearable sensors have received considerable interest over the past decade owing to their tremendous promise for monitoring the wearers’ health, fitness, and their surroundings. However, only limited attention has been directed at developing wearable chemical sensors that offer more comprehensive information about a wearer’s well-being. The development of wearable chemical sensors faces multiple challenges on various fronts. This perspective reviews key challenges and technological gaps impeding the successful realization of effective wearable chemical sensor systems, related to materials, power, analytical procedure, communication, data acquisition, processing, and security. Size, rigidity, and operational requirements of present chemical sensors are incompatible with wearable technology. Sensor stability and on-body sensor surface regeneration constitute key analytical challenges. Similarly, present wearable power sources are incapable of meeting the requirements for wearable electronics owing to their l...
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paper_title: Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

paper_content:

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.
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paper_title: Simulating 2368 temperate lakes reveals weak coherence in stratification phenology

paper_content:

Changes in water temperatures resulting from climate warming can alter the structure and function of aquatic ecosystems. Lake-specific physical characteristics may play a role in mediating individual lake responses to climate. Past mechanistic studies of lake–climate interactions have simulated generic lake classes at large spatial scales or performed detailed analyses of small numbers of real lakes. Understanding the diversity of lake responses to climate change across landscapes requires a hybrid approach that couples site-specific lake characteristics with broad-scale environmental drivers. This study provides a substantial advancement in lake ecosystem modeling by combining open-source tools with freely available continental-scale data to mechanistically model daily temperatures for 2368 Wisconsin lakes over three decades (1979–2011). The model accurately predicted observed surface layer temperatures (RMSE: 1.74°C) and the presence/absence of stratification (81.1% agreement). Among-lake coherence was strong for surface temperatures and weak for the timing of stratification, suggesting individual lake characteristics mediate some – but not all – ecologically relevant lake responses to climate.
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paper_title: Large-scale modeled contemporary and future water temperature estimates for 10774 Midwestern U.S. Lakes

paper_content:

Climate change has already influenced lake temperatures globally, but understanding future change is challenging. The response of lakes to changing climate drivers is complex due to the nature of lake-atmosphere coupling, ice cover, and stratification. To better understand the diversity of lake responses to climate change and give managers insight on individual lakes, we modelled daily water temperature profiles for 10,774 lakes in Michigan, Minnesota, and Wisconsin for contemporary (1979–2015) and future (2020–2040 and 2080–2100) time periods with climate models based on the Representative Concentration Pathway 8.5, the worst-case emission scenario. In addition to lake-specific daily simulated temperatures, we derived commonly used, ecologically relevant annual metrics of thermal conditions for each lake. We include all supporting lake-specific model parameters, meteorological drivers, and archived code for the model and derived metric calculations. This unique dataset offers landscape-level insight into the impact of climate change on lakes. Machine-accessible metadata file describing the reported data (ISA-Tab format)
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paper_title: Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

paper_content:

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.
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paper_title: Understanding Neural Networks Through Deep Visualization

paper_content:

Recent years have produced great advances in training large, deep neural networks (DNNs), including notable successes in training convolutional neural networks (convnets) to recognize natural images. However, our understanding of how these models work, especially what computations they perform at intermediate layers, has lagged behind. Progress in the field will be further accelerated by the development of better tools for visualizing and interpreting neural nets. We introduce two such tools here. The first is a tool that visualizes the activations produced on each layer of a trained convnet as it processes an image or video (e.g. a live webcam stream). We have found that looking at live activations that change in response to user input helps build valuable intuitions about how convnets work. The second tool enables visualizing features at each layer of a DNN via regularized optimization in image space. Because previous versions of this idea produced less recognizable images, here we introduce several new regularization methods that combine to produce qualitatively clearer, more interpretable visualizations. Both tools are open source and work on a pre-trained convnet with minimal setup.
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paper_title: Clinical chemistry in higher dimensions: Machine-learning and enhanced prediction from routine clinical chemistry data.

paper_content:

Big Data is having an impact on many areas of research, not the least of which is biomedical science. In this review paper, big data and machine learning are defined in terms accessible to the clinical chemistry community. Seven myths associated with machine learning and big data are then presented, with the aim of managing expectation of machine learning amongst clinical chemists. The myths are illustrated with four examples investigating the relationship between biomarkers in liver function tests, enhanced laboratory prediction of hepatitis virus infection, the relationship between bilirubin and white cell count, and the relationship between red cell distribution width and laboratory prediction of anaemia.
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Title: A survey on Big Data and Machine Learning for Chemistry

Section 1: Introduction
Description 1: This section will introduce the ongoing revolution with artificial intelligence, particularly focusing on machine learning and big data in the context of chemistry, and laying out its potential impacts on the field.

Section 2: Machine learning (ML)
Description 2: This section will explore the standard approaches in machine learning, highlighting how ML algorithms operate, their requirements, and their applications in chemistry.

Section 3: An overview of Deep Learning
Description 3: This section will provide an overview of deep learning techniques, their recent advancements, and their applications in handling complex problems within chemistry.

Section 4: The flow path towards data-based scientific discovery in chemistry
Description 4: This section will describe the standard flow path from data production to outcome applications of machine learning in chemistry, including steps like data pre-processing, training, and application of learned models.

Section 5: Materials Discovery
Description 5: This section will discuss the computational tools and methodologies used to discover new materials and evaluate their properties, highlighting big data and ML applications in this area.

Section 6: Large Databases and Initiatives
Description 6: This section will review major initiatives and databases that support big data and machine learning applications in chemistry and materials science, emphasizing collaborative platforms and their importance.

Section 7: Identification of compounds with genetic algorithms
Description 7: This section will explain the use of bio-inspired computation, particularly genetic algorithms, for optimizing and discovering chemical compounds.

Section 8: Synthesis prediction using ML
Description 8: This section will discuss machine learning approaches for predicting the synthesis of new compounds in organic chemistry.

Section 9: Quantum chemistry
Description 9: This section will focus on the high computational costs of quantum chemistry and how machine learning is being employed to supplement and enhance quantum mechanical calculations.

Section 10: Computer-aided Drug Design
Description 10: This section will provide insights into the use of computational methods, including quantum chemistry properties and high-throughput analysis, to design new drugs.

Section 11: Sensors and Biosensors for Intelligent Systems and Internet of Things
Description 11: This section will discuss the role of chemical sensors and biosensors in the Internet of Things (IoT) and intelligent systems, highlighting their importance in providing data for big data and ML applications.

Section 12: Current Limitations and Future Outlook
Description 12: This section will identify the current limitations and challenges in the field, offering a critical analysis and discussing potential future advancements in the use of big data and machine learning in chemistry.