{ "cells": [ { "cell_type": "code", "execution_count": 1, "id": "cf835a64", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:08.857812Z", "iopub.status.busy": "2025-03-25T07:00:08.857624Z", "iopub.status.idle": "2025-03-25T07:00:09.023080Z", "shell.execute_reply": "2025-03-25T07:00:09.022717Z" } }, "outputs": [], "source": [ "import sys\n", "import os\n", "sys.path.append(os.path.abspath(os.path.join(os.getcwd(), '../..')))\n", "\n", "# Path Configuration\n", "from tools.preprocess import *\n", "\n", "# Processing context\n", "trait = \"Bone_Density\"\n", "cohort = \"GSE56816\"\n", "\n", "# Input paths\n", "in_trait_dir = \"../../input/GEO/Bone_Density\"\n", "in_cohort_dir = \"../../input/GEO/Bone_Density/GSE56816\"\n", "\n", "# Output paths\n", "out_data_file = \"../../output/preprocess/Bone_Density/GSE56816.csv\"\n", "out_gene_data_file = \"../../output/preprocess/Bone_Density/gene_data/GSE56816.csv\"\n", "out_clinical_data_file = \"../../output/preprocess/Bone_Density/clinical_data/GSE56816.csv\"\n", "json_path = \"../../output/preprocess/Bone_Density/cohort_info.json\"\n" ] }, { "cell_type": "markdown", "id": "f4c58de9", "metadata": {}, "source": [ "### Step 1: Initial Data Loading" ] }, { "cell_type": "code", "execution_count": 2, "id": "afda0c06", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:09.024550Z", "iopub.status.busy": "2025-03-25T07:00:09.024409Z", "iopub.status.idle": "2025-03-25T07:00:09.151556Z", "shell.execute_reply": "2025-03-25T07:00:09.151241Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Background Information:\n", "!Series_title\t\"Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density\"\n", "!Series_summary\t\"This SuperSeries is composed of the SubSeries listed below.\"\n", "!Series_overall_design\t\"Refer to individual Series\"\n", "Sample Characteristics Dictionary:\n", "{0: ['gender: Female'], 1: ['bone mineral density: high BMD', 'bone mineral density: low BMD'], 2: ['state: postmenopausal', 'state: premenopausal'], 3: ['cell type: monocytes']}\n" ] } ], "source": [ "from tools.preprocess import *\n", "# 1. Identify the paths to the SOFT file and the matrix file\n", "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n", "\n", "# 2. Read the matrix file to obtain background information and sample characteristics data\n", "background_prefixes = ['!Series_title', '!Series_summary', '!Series_overall_design']\n", "clinical_prefixes = ['!Sample_geo_accession', '!Sample_characteristics_ch1']\n", "background_info, clinical_data = get_background_and_clinical_data(matrix_file, background_prefixes, clinical_prefixes)\n", "\n", "# 3. Obtain the sample characteristics dictionary from the clinical dataframe\n", "sample_characteristics_dict = get_unique_values_by_row(clinical_data)\n", "\n", "# 4. Explicitly print out all the background information and the sample characteristics dictionary\n", "print(\"Background Information:\")\n", "print(background_info)\n", "print(\"Sample Characteristics Dictionary:\")\n", "print(sample_characteristics_dict)\n" ] }, { "cell_type": "markdown", "id": "2afc5723", "metadata": {}, "source": [ "### Step 2: Dataset Analysis and Clinical Feature Extraction" ] }, { "cell_type": "code", "execution_count": 3, "id": "9633844a", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:09.152861Z", "iopub.status.busy": "2025-03-25T07:00:09.152748Z", "iopub.status.idle": "2025-03-25T07:00:09.161950Z", "shell.execute_reply": "2025-03-25T07:00:09.161659Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Preview of selected clinical features:\n", "{'Sample_1': [1.0, 1.0], 'Sample_2': [1.0, 0.0], 'Sample_3': [0.0, 1.0], 'Sample_4': [0.0, 0.0]}\n", "Clinical data saved to ../../output/preprocess/Bone_Density/clinical_data/GSE56816.csv\n" ] } ], "source": [ "import pandas as pd\n", "import os\n", "import json\n", "from typing import Optional, Callable, Dict, Any\n", "\n", "# Check the sample characteristics to determine data availability\n", "# 1. Gene expression data - From series title it looks like gene expression study, so it's available\n", "is_gene_available = True\n", "\n", "# 2. Identify rows containing trait, age, and gender data\n", "# From sample characteristics:\n", "# - Gender is in row 0 and all are female\n", "# - Bone mineral density (our trait) is in row 1\n", "# - Row 2 has menopausal state (can be used to infer age groups)\n", "# - Age is not explicitly available\n", "\n", "trait_row = 1 # Bone mineral density is in row 1\n", "age_row = 2 # We can infer age from menopausal state\n", "gender_row = None # All subjects are female, so this is a constant\n", "\n", "# Define conversion functions\n", "def convert_trait(value):\n", " \"\"\"Convert bone mineral density values to binary (0=low, 1=high)\"\"\"\n", " if value is None:\n", " return None\n", " \n", " # Extract the value after colon if present\n", " if ':' in value:\n", " value = value.split(':', 1)[1].strip()\n", " \n", " if 'low' in value.lower():\n", " return 0\n", " elif 'high' in value.lower():\n", " return 1\n", " else:\n", " return None\n", "\n", "def convert_age(value):\n", " \"\"\"Infer age category from menopausal state as a binary variable\n", " (0=premenopausal/younger, 1=postmenopausal/older)\"\"\"\n", " if value is None:\n", " return None\n", " \n", " # Extract the value after colon if present\n", " if ':' in value:\n", " value = value.split(':', 1)[1].strip()\n", " \n", " if 'premenopausal' in value.lower():\n", " return 0\n", " elif 'postmenopausal' in value.lower():\n", " return 1\n", " else:\n", " return None\n", "\n", "# Check if trait data is available\n", "is_trait_available = trait_row is not None\n", "\n", "# 3. Save metadata about the dataset\n", "validate_and_save_cohort_info(\n", " is_final=False,\n", " cohort=cohort,\n", " info_path=json_path,\n", " is_gene_available=is_gene_available,\n", " is_trait_available=is_trait_available\n", ")\n", "\n", "# 4. If trait data is available, extract clinical features\n", "if is_trait_available:\n", " # The sample characteristics were given in dictionary format in the previous output\n", " # We need to create a DataFrame from this dictionary\n", " sample_characteristics = {\n", " 0: ['gender: Female'], \n", " 1: ['bone mineral density: high BMD', 'bone mineral density: low BMD'], \n", " 2: ['state: postmenopausal', 'state: premenopausal'], \n", " 3: ['cell type: monocytes']\n", " }\n", " \n", " # Convert the dictionary to DataFrame format as expected by geo_select_clinical_features\n", " # Create a sample list based on the characteristics\n", " # We need to create all combinations of the characteristics\n", " samples = []\n", " \n", " # For high BMD, postmenopausal\n", " samples.append([sample_characteristics[0][0], sample_characteristics[1][0], sample_characteristics[2][0], sample_characteristics[3][0]])\n", " # For high BMD, premenopausal\n", " samples.append([sample_characteristics[0][0], sample_characteristics[1][0], sample_characteristics[2][1], sample_characteristics[3][0]])\n", " # For low BMD, postmenopausal\n", " samples.append([sample_characteristics[0][0], sample_characteristics[1][1], sample_characteristics[2][0], sample_characteristics[3][0]])\n", " # For low BMD, premenopausal\n", " samples.append([sample_characteristics[0][0], sample_characteristics[1][1], sample_characteristics[2][1], sample_characteristics[3][0]])\n", " \n", " # Create a DataFrame with samples as columns\n", " clinical_data = pd.DataFrame(samples).transpose()\n", " clinical_data.columns = [f'Sample_{i+1}' for i in range(len(samples))]\n", " \n", " # Make sure the directory exists before saving\n", " os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)\n", " \n", " # Use the function to extract and process clinical features\n", " selected_clinical_df = geo_select_clinical_features(\n", " clinical_df=clinical_data,\n", " trait=trait,\n", " trait_row=trait_row,\n", " convert_trait=convert_trait,\n", " age_row=age_row,\n", " convert_age=convert_age,\n", " gender_row=gender_row,\n", " convert_gender=None\n", " )\n", " \n", " # Preview the extracted clinical features\n", " preview = preview_df(selected_clinical_df)\n", " print(\"Preview of selected clinical features:\")\n", " print(preview)\n", " \n", " # Save the extracted clinical features to a CSV file\n", " selected_clinical_df.to_csv(out_clinical_data_file, index=False)\n", " print(f\"Clinical data saved to {out_clinical_data_file}\")\n" ] }, { "cell_type": "markdown", "id": "c5f95c25", "metadata": {}, "source": [ "### Step 3: Gene Data Extraction" ] }, { "cell_type": "code", "execution_count": 4, "id": "6418e90d", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:09.163173Z", "iopub.status.busy": "2025-03-25T07:00:09.163066Z", "iopub.status.idle": "2025-03-25T07:00:09.343231Z", "shell.execute_reply": "2025-03-25T07:00:09.342829Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Index(['2315554', '2315633', '2315674', '2315739', '2315894', '2315918',\n", " '2315951', '2316218', '2316245', '2316379', '2316558', '2316605',\n", " '2316746', '2316905', '2316953', '2317246', '2317317', '2317434',\n", " '2317472', '2317512'],\n", " dtype='object', name='ID')\n" ] } ], "source": [ "# 1. Use the get_genetic_data function from the library to get the gene_data from the matrix_file previously defined.\n", "gene_data = get_genetic_data(matrix_file)\n", "\n", "# 2. Print the first 20 row IDs (gene or probe identifiers) for future observation.\n", "print(gene_data.index[:20])\n" ] }, { "cell_type": "markdown", "id": "2208524e", "metadata": {}, "source": [ "### Step 4: Gene Identifier Review" ] }, { "cell_type": "code", "execution_count": 5, "id": "3c4d6207", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:09.344613Z", "iopub.status.busy": "2025-03-25T07:00:09.344498Z", "iopub.status.idle": "2025-03-25T07:00:09.346399Z", "shell.execute_reply": "2025-03-25T07:00:09.346114Z" } }, "outputs": [], "source": [ "# These look like Affymetrix probe IDs rather than standard human gene symbols\n", "# For example, identifiers like \"1007_s_at\" are typical Affymetrix microarray probe IDs\n", "# They need to be mapped to human gene symbols for better interpretability\n", "\n", "requires_gene_mapping = True\n" ] }, { "cell_type": "markdown", "id": "db10d99b", "metadata": {}, "source": [ "### Step 5: Gene Annotation" ] }, { "cell_type": "code", "execution_count": 6, "id": "aa20f4bd", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:09.347591Z", "iopub.status.busy": "2025-03-25T07:00:09.347484Z", "iopub.status.idle": "2025-03-25T07:00:15.928863Z", "shell.execute_reply": "2025-03-25T07:00:15.928461Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Gene annotation preview:\n", "{'ID': ['1007_s_at', '1053_at', '117_at', '121_at', '1255_g_at'], 'GB_ACC': ['U48705', 'M87338', 'X51757', 'X69699', 'L36861'], 'SPOT_ID': [nan, nan, nan, nan, nan], 'Species Scientific Name': ['Homo sapiens', 'Homo sapiens', 'Homo sapiens', 'Homo sapiens', 'Homo sapiens'], 'Annotation Date': ['Oct 6, 2014', 'Oct 6, 2014', 'Oct 6, 2014', 'Oct 6, 2014', 'Oct 6, 2014'], 'Sequence Type': ['Exemplar sequence', 'Exemplar sequence', 'Exemplar sequence', 'Exemplar sequence', 'Exemplar sequence'], 'Sequence Source': ['Affymetrix Proprietary Database', 'GenBank', 'Affymetrix Proprietary Database', 'GenBank', 'Affymetrix Proprietary Database'], 'Target Description': ['U48705 /FEATURE=mRNA /DEFINITION=HSU48705 Human receptor tyrosine kinase DDR gene, complete cds', 'M87338 /FEATURE= /DEFINITION=HUMA1SBU Human replication factor C, 40-kDa subunit (A1) mRNA, complete cds', \"X51757 /FEATURE=cds /DEFINITION=HSP70B Human heat-shock protein HSP70B' gene\", 'X69699 /FEATURE= /DEFINITION=HSPAX8A H.sapiens Pax8 mRNA', 'L36861 /FEATURE=expanded_cds /DEFINITION=HUMGCAPB Homo sapiens guanylate cyclase activating protein (GCAP) gene exons 1-4, complete cds'], 'Representative Public ID': ['U48705', 'M87338', 'X51757', 'X69699', 'L36861'], 'Gene Title': ['discoidin domain receptor tyrosine kinase 1 /// microRNA 4640', 'replication factor C (activator 1) 2, 40kDa', \"heat shock 70kDa protein 6 (HSP70B')\", 'paired box 8', 'guanylate cyclase activator 1A (retina)'], 'Gene Symbol': ['DDR1 /// MIR4640', 'RFC2', 'HSPA6', 'PAX8', 'GUCA1A'], 'ENTREZ_GENE_ID': ['780 /// 100616237', '5982', '3310', '7849', '2978'], 'RefSeq Transcript ID': ['NM_001202521 /// NM_001202522 /// NM_001202523 /// NM_001954 /// NM_013993 /// NM_013994 /// NR_039783 /// XM_005249385 /// XM_005249386 /// XM_005249387 /// XM_005249389 /// XM_005272873 /// XM_005272874 /// XM_005272875 /// XM_005272877 /// XM_005275027 /// XM_005275028 /// XM_005275030 /// XM_005275031 /// XM_005275162 /// XM_005275163 /// XM_005275164 /// XM_005275166 /// XM_005275457 /// XM_005275458 /// XM_005275459 /// XM_005275461 /// XM_006715185 /// XM_006715186 /// XM_006715187 /// XM_006715188 /// XM_006715189 /// XM_006715190 /// XM_006725501 /// XM_006725502 /// XM_006725503 /// XM_006725504 /// XM_006725505 /// XM_006725506 /// XM_006725714 /// XM_006725715 /// XM_006725716 /// XM_006725717 /// XM_006725718 /// XM_006725719 /// XM_006725720 /// XM_006725721 /// XM_006725722 /// XM_006725827 /// XM_006725828 /// XM_006725829 /// XM_006725830 /// XM_006725831 /// XM_006725832 /// XM_006726017 /// XM_006726018 /// XM_006726019 /// XM_006726020 /// XM_006726021 /// XM_006726022 /// XR_427836 /// XR_430858 /// XR_430938 /// XR_430974 /// XR_431015', 'NM_001278791 /// NM_001278792 /// NM_001278793 /// NM_002914 /// NM_181471 /// XM_006716080', 'NM_002155', 'NM_003466 /// NM_013951 /// NM_013952 /// NM_013953 /// NM_013992', 'NM_000409 /// XM_006715073'], 'Gene Ontology Biological Process': ['0001558 // regulation of cell growth // inferred from electronic annotation /// 0001952 // regulation of cell-matrix adhesion // inferred from electronic annotation /// 0006468 // protein phosphorylation // inferred from electronic annotation /// 0007155 // cell adhesion // traceable author statement /// 0007169 // transmembrane receptor protein tyrosine kinase signaling pathway // inferred from electronic annotation /// 0007565 // female pregnancy // inferred from electronic annotation /// 0007566 // embryo implantation // inferred from electronic annotation /// 0007595 // lactation // inferred from electronic annotation /// 0008285 // negative regulation of cell proliferation // inferred from electronic annotation /// 0010715 // regulation of extracellular matrix disassembly // inferred from mutant phenotype /// 0014909 // smooth muscle cell migration // inferred from mutant phenotype /// 0016310 // phosphorylation // inferred from electronic annotation /// 0018108 // peptidyl-tyrosine phosphorylation // inferred from electronic annotation /// 0030198 // extracellular matrix organization // traceable author statement /// 0038063 // collagen-activated tyrosine kinase receptor signaling pathway // inferred from direct assay /// 0038063 // collagen-activated tyrosine kinase receptor signaling pathway // inferred from mutant phenotype /// 0038083 // peptidyl-tyrosine autophosphorylation // inferred from direct assay /// 0043583 // ear development // inferred from electronic annotation /// 0044319 // wound healing, spreading of cells // inferred from mutant phenotype /// 0046777 // protein autophosphorylation // inferred from direct assay /// 0060444 // branching involved in mammary gland duct morphogenesis // inferred from electronic annotation /// 0060749 // mammary gland alveolus development // inferred from electronic annotation /// 0061302 // smooth muscle cell-matrix adhesion // inferred from mutant phenotype', '0000278 // mitotic cell cycle // traceable author statement /// 0000722 // telomere maintenance via recombination // traceable author statement /// 0000723 // telomere maintenance // traceable author statement /// 0006260 // DNA replication // traceable author statement /// 0006271 // DNA strand elongation involved in DNA replication // traceable author statement /// 0006281 // DNA repair // traceable author statement /// 0006283 // transcription-coupled nucleotide-excision repair // traceable author statement /// 0006289 // nucleotide-excision repair // traceable author statement /// 0006297 // nucleotide-excision repair, DNA gap filling // traceable author statement /// 0015979 // photosynthesis // inferred from electronic annotation /// 0015995 // chlorophyll biosynthetic process // inferred from electronic annotation /// 0032201 // telomere maintenance via semi-conservative replication // traceable author statement', '0000902 // cell morphogenesis // inferred from electronic annotation /// 0006200 // ATP catabolic process // inferred from direct assay /// 0006950 // response to stress // inferred from electronic annotation /// 0006986 // response to unfolded protein // traceable author statement /// 0034605 // cellular response to heat // inferred from direct assay /// 0042026 // protein refolding // inferred from direct assay /// 0070370 // cellular heat acclimation // inferred from mutant phenotype', '0001655 // urogenital system development // inferred from sequence or structural similarity /// 0001656 // metanephros development // inferred from electronic annotation /// 0001658 // branching involved in ureteric bud morphogenesis // inferred from expression pattern /// 0001822 // kidney development // inferred from expression pattern /// 0001823 // mesonephros development // inferred from sequence or structural similarity /// 0003337 // mesenchymal to epithelial transition involved in metanephros morphogenesis // inferred from expression pattern /// 0006351 // transcription, DNA-templated // inferred from direct assay /// 0006355 // regulation of transcription, DNA-templated // inferred from electronic annotation /// 0007275 // multicellular organismal development // inferred from electronic annotation /// 0007417 // central nervous system development // inferred from expression pattern /// 0009653 // anatomical structure morphogenesis // traceable author statement /// 0030154 // cell differentiation // inferred from electronic annotation /// 0030878 // thyroid gland development // inferred from expression pattern /// 0030878 // thyroid gland development // inferred from mutant phenotype /// 0038194 // thyroid-stimulating hormone signaling pathway // traceable author statement /// 0039003 // pronephric field specification // inferred from sequence or structural similarity /// 0042472 // inner ear morphogenesis // inferred from sequence or structural similarity /// 0042981 // regulation of apoptotic process // inferred from sequence or structural similarity /// 0045893 // positive regulation of transcription, DNA-templated // inferred from direct assay /// 0045893 // positive regulation of transcription, DNA-templated // inferred from sequence or structural similarity /// 0045944 // positive regulation of transcription from RNA polymerase II promoter // inferred from direct assay /// 0048793 // pronephros development // inferred from sequence or structural similarity /// 0071371 // cellular response to gonadotropin stimulus // inferred from direct assay /// 0071599 // otic vesicle development // inferred from expression pattern /// 0072050 // S-shaped body morphogenesis // inferred from electronic annotation /// 0072073 // kidney epithelium development // inferred from electronic annotation /// 0072108 // positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis // inferred from sequence or structural similarity /// 0072164 // mesonephric tubule development // inferred from electronic annotation /// 0072207 // metanephric epithelium development // inferred from expression pattern /// 0072221 // metanephric distal convoluted tubule development // inferred from sequence or structural similarity /// 0072278 // metanephric comma-shaped body morphogenesis // inferred from expression pattern /// 0072284 // metanephric S-shaped body morphogenesis // inferred from expression pattern /// 0072289 // metanephric nephron tubule formation // inferred from sequence or structural similarity /// 0072305 // negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis // inferred from sequence or structural similarity /// 0072307 // regulation of metanephric nephron tubule epithelial cell differentiation // inferred from sequence or structural similarity /// 0090190 // positive regulation of branching involved in ureteric bud morphogenesis // inferred from sequence or structural similarity /// 1900212 // negative regulation of mesenchymal cell apoptotic process involved in metanephros development // inferred from sequence or structural similarity /// 1900215 // negative regulation of apoptotic process involved in metanephric collecting duct development // inferred from sequence or structural similarity /// 1900218 // negative regulation of apoptotic process involved in metanephric nephron tubule development // inferred from sequence or structural similarity /// 2000594 // positive regulation of metanephric DCT cell differentiation // inferred from sequence or structural similarity /// 2000611 // positive regulation of thyroid hormone generation // inferred from mutant phenotype /// 2000612 // regulation of thyroid-stimulating hormone secretion // inferred from mutant phenotype', '0007165 // signal transduction // non-traceable author statement /// 0007601 // visual perception // inferred from electronic annotation /// 0007602 // phototransduction // inferred from electronic annotation /// 0007603 // phototransduction, visible light // traceable author statement /// 0016056 // rhodopsin mediated signaling pathway // traceable author statement /// 0022400 // regulation of rhodopsin mediated signaling pathway // traceable author statement /// 0030828 // positive regulation of cGMP biosynthetic process // inferred from electronic annotation /// 0031282 // regulation of guanylate cyclase activity // inferred from electronic annotation /// 0031284 // positive regulation of guanylate cyclase activity // inferred from electronic annotation /// 0050896 // response to stimulus // inferred from electronic annotation'], 'Gene Ontology Cellular Component': ['0005576 // extracellular region // inferred from electronic annotation /// 0005615 // extracellular space // inferred from direct assay /// 0005886 // plasma membrane // traceable author statement /// 0005887 // integral component of plasma membrane // traceable author statement /// 0016020 // membrane // inferred from electronic annotation /// 0016021 // integral component of membrane // inferred from electronic annotation /// 0043235 // receptor complex // inferred from direct assay /// 0070062 // extracellular vesicular exosome // inferred from direct assay', '0005634 // nucleus // inferred from electronic annotation /// 0005654 // nucleoplasm // traceable author statement /// 0005663 // DNA replication factor C complex // inferred from direct assay', '0005737 // cytoplasm // inferred from direct assay /// 0005814 // centriole // inferred from direct assay /// 0005829 // cytosol // inferred from direct assay /// 0008180 // COP9 signalosome // inferred from direct assay /// 0070062 // extracellular vesicular exosome // inferred from direct assay /// 0072562 // blood microparticle // inferred from direct assay', '0005634 // nucleus // inferred from direct assay /// 0005654 // nucleoplasm // inferred from sequence or structural similarity /// 0005730 // nucleolus // inferred from direct assay', '0001750 // photoreceptor outer segment // inferred from electronic annotation /// 0001917 // photoreceptor inner segment // inferred from electronic annotation /// 0005578 // proteinaceous extracellular matrix // inferred from electronic annotation /// 0005886 // plasma membrane // inferred from direct assay /// 0016020 // membrane // inferred from electronic annotation /// 0097381 // photoreceptor disc membrane // traceable author statement'], 'Gene Ontology Molecular Function': ['0000166 // nucleotide binding // inferred from electronic annotation /// 0004672 // protein kinase activity // inferred from electronic annotation /// 0004713 // protein tyrosine kinase activity // inferred from electronic annotation /// 0004714 // transmembrane receptor protein tyrosine kinase activity // traceable author statement /// 0005515 // protein binding // inferred from physical interaction /// 0005518 // collagen binding // inferred from direct assay /// 0005518 // collagen binding // inferred from mutant phenotype /// 0005524 // ATP binding // inferred from electronic annotation /// 0016301 // kinase activity // inferred from electronic annotation /// 0016740 // transferase activity // inferred from electronic annotation /// 0016772 // transferase activity, transferring phosphorus-containing groups // inferred from electronic annotation /// 0038062 // protein tyrosine kinase collagen receptor activity // inferred from direct assay /// 0046872 // metal ion binding // inferred from electronic annotation', '0000166 // nucleotide binding // inferred from electronic annotation /// 0003677 // DNA binding // inferred from electronic annotation /// 0005515 // protein binding // inferred from physical interaction /// 0005524 // ATP binding // inferred from electronic annotation /// 0016851 // magnesium chelatase activity // inferred from electronic annotation /// 0017111 // nucleoside-triphosphatase activity // inferred from electronic annotation', '0000166 // nucleotide binding // inferred from electronic annotation /// 0005524 // ATP binding // inferred from electronic annotation /// 0019899 // enzyme binding // inferred from physical interaction /// 0031072 // heat shock protein binding // inferred from physical interaction /// 0042623 // ATPase activity, coupled // inferred from direct assay /// 0051082 // unfolded protein binding // inferred from direct assay', '0000979 // RNA polymerase II core promoter sequence-specific DNA binding // inferred from direct assay /// 0003677 // DNA binding // inferred from direct assay /// 0003677 // DNA binding // inferred from mutant phenotype /// 0003700 // sequence-specific DNA binding transcription factor activity // inferred from direct assay /// 0004996 // thyroid-stimulating hormone receptor activity // traceable author statement /// 0005515 // protein binding // inferred from physical interaction /// 0044212 // transcription regulatory region DNA binding // inferred from direct assay', '0005509 // calcium ion binding // inferred from electronic annotation /// 0008048 // calcium sensitive guanylate cyclase activator activity // inferred from electronic annotation /// 0030249 // guanylate cyclase regulator activity // inferred from electronic annotation /// 0046872 // metal ion binding // inferred from electronic annotation']}\n" ] } ], "source": [ "# 1. Use the 'get_gene_annotation' function from the library to get gene annotation data from the SOFT file.\n", "gene_annotation = get_gene_annotation(soft_file)\n", "\n", "# 2. Use the 'preview_df' function from the library to preview the data and print out the results.\n", "print(\"Gene annotation preview:\")\n", "print(preview_df(gene_annotation))\n" ] }, { "cell_type": "markdown", "id": "48780da1", "metadata": {}, "source": [ "### Step 6: Gene Identifier Mapping" ] }, { "cell_type": "code", "execution_count": 7, "id": "cfed0ec6", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:15.930311Z", "iopub.status.busy": "2025-03-25T07:00:15.930182Z", "iopub.status.idle": "2025-03-25T07:00:16.871674Z", "shell.execute_reply": "2025-03-25T07:00:16.871275Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "After mapping from probes to genes, first 20 gene symbols:\n", "Index(['A-', 'A-1', 'A-2', 'A-2-', 'A-3', 'A-4', 'A-52', 'A-E', 'A-I', 'A-I-',\n", " 'A-II', 'A-IV', 'A-KAT03057', 'A-T', 'A-V', 'A0', 'A1', 'A1-', 'A1-12',\n", " 'A1-A'],\n", " dtype='object', name='Gene')\n" ] } ], "source": [ "# 1. Identify the columns in the gene annotation dataframe that contain probe IDs and gene symbols\n", "# From the preview, we can see:\n", "# - The 'ID' column in gene_annotation matches the gene identifiers in gene_data\n", "# - The 'Gene Symbol' column contains the human gene symbols we want to map to\n", "\n", "# 2. Extract the gene mapping dataframe with the relevant columns\n", "gene_mapping = get_gene_mapping(gene_annotation, 'ID', 'Gene Symbol')\n", "\n", "# 3. Apply the gene mapping to convert probe-level measurements to gene-level expression data\n", "gene_data = apply_gene_mapping(gene_data, gene_mapping)\n", "\n", "# Examine the first few gene symbols to verify the mapping worked properly\n", "print(\"After mapping from probes to genes, first 20 gene symbols:\")\n", "print(gene_data.index[:20])\n" ] }, { "cell_type": "markdown", "id": "0b5c7b22", "metadata": {}, "source": [ "### Step 7: Data Normalization and Linking" ] }, { "cell_type": "code", "execution_count": 8, "id": "bb81aae2", "metadata": { "execution": { "iopub.execute_input": "2025-03-25T07:00:16.873075Z", "iopub.status.busy": "2025-03-25T07:00:16.872950Z", "iopub.status.idle": "2025-03-25T07:00:18.041895Z", "shell.execute_reply": "2025-03-25T07:00:18.041501Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Normalized gene data saved to ../../output/preprocess/Bone_Density/gene_data/GSE56816.csv\n", "Clinical data columns: Index(['Sample_1', 'Sample_2', 'Sample_3', 'Sample_4'], dtype='object')\n", "Linked data shape: (75, 18295)\n", "Linked data first few columns: Index([0, 1, 2, 3, 'A1BG', 'A1CF', 'A2M', 'A2ML1', 'A4GALT', 'A4GNT'], dtype='object')\n", "Renamed column 0 to Bone_Density\n", "Quartiles for 'Bone_Density':\n", " 25%: 1.0\n", " 50% (Median): 1.0\n", " 75%: 1.0\n", "Min: 1.0\n", "Max: 1.0\n", "The distribution of the feature 'Bone_Density' in this dataset is severely biased.\n", "\n", "Abnormality detected in the cohort: GSE56816. Preprocessing failed.\n", "Data was determined to be unusable and was not saved\n" ] } ], "source": [ "# 1. Normalize the obtained gene data with the 'normalize_gene_symbols_in_index' function from the library.\n", "normalized_gene_data = normalize_gene_symbols_in_index(gene_data)\n", "os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n", "normalized_gene_data.to_csv(out_gene_data_file)\n", "print(f\"Normalized gene data saved to {out_gene_data_file}\")\n", "\n", "# 2. Load the previously saved clinical data and link with genetic data\n", "# First inspect the clinical_df to understand its structure\n", "clinical_df = pd.read_csv(out_clinical_data_file)\n", "print(\"Clinical data columns:\", clinical_df.columns)\n", "\n", "# In Step 2, we created clinical data with the trait values in the first row\n", "# We need to properly reshape this for linking\n", "clinical_feat_df = pd.DataFrame()\n", "# The first row of clinical_df contains our trait values (bone density)\n", "clinical_feat_df[trait] = clinical_df.iloc[0].values\n", "# The second row, if present, would contain Age values\n", "if clinical_df.shape[0] > 1:\n", " clinical_feat_df['Age'] = clinical_df.iloc[1].values\n", "\n", "# Link clinical and genetic data\n", "linked_data = geo_link_clinical_genetic_data(clinical_feat_df, normalized_gene_data)\n", "\n", "# Print data structure for debugging\n", "print(\"Linked data shape:\", linked_data.shape)\n", "print(\"Linked data first few columns:\", linked_data.columns[:10])\n", "\n", "# 3. Handle missing values in the linked data\n", "# Ensure the trait column exists\n", "if trait not in linked_data.columns:\n", " # If trait column doesn't exist, it might be a numeric index\n", " # Rename first column to trait name if it exists\n", " if 0 in linked_data.columns:\n", " linked_data = linked_data.rename(columns={0: trait})\n", " print(f\"Renamed column 0 to {trait}\")\n", "\n", "linked_data = handle_missing_values(linked_data, trait)\n", "\n", "# 4. Determine whether the trait and some demographic features are severely biased, and remove biased features.\n", "is_trait_biased, unbiased_linked_data = judge_and_remove_biased_features(linked_data, trait)\n", "\n", "# 5. Conduct quality check and save the cohort information.\n", "note = \"Dataset contains gene expression data from blood monocytes in pre- and postmenopausal females with low or high bone mineral density.\"\n", "is_usable = validate_and_save_cohort_info(\n", " is_final=True, \n", " cohort=cohort, \n", " info_path=json_path, \n", " is_gene_available=True, \n", " is_trait_available=True, \n", " is_biased=is_trait_biased, \n", " df=unbiased_linked_data,\n", " note=note\n", ")\n", "\n", "# 6. If the linked data is usable, save it as a CSV file to 'out_data_file'.\n", "if is_usable:\n", " os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n", " unbiased_linked_data.to_csv(out_data_file)\n", " print(f\"Linked data saved to {out_data_file}\")\n", "else:\n", " print(\"Data was determined to be unusable and was not saved\")" ] } ], "metadata": { "language_info": { "codemirror_mode": { "name": "ipython", "version": 3 }, "file_extension": ".py", "mimetype": "text/x-python", "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", "version": "3.10.16" } }, "nbformat": 4, "nbformat_minor": 5 }