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{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "147aed01",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.548956Z",
     "iopub.status.busy": "2025-03-25T08:25:56.548720Z",
     "iopub.status.idle": "2025-03-25T08:25:56.716341Z",
     "shell.execute_reply": "2025-03-25T08:25:56.716010Z"
    }
   },
   "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 = \"Congestive_heart_failure\"\n",
    "cohort = \"GSE93101\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Congestive_heart_failure\"\n",
    "in_cohort_dir = \"../../input/GEO/Congestive_heart_failure/GSE93101\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Congestive_heart_failure/GSE93101.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Congestive_heart_failure/gene_data/GSE93101.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Congestive_heart_failure/clinical_data/GSE93101.csv\"\n",
    "json_path = \"../../output/preprocess/Congestive_heart_failure/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "6f2b768c",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "09762be8",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.717676Z",
     "iopub.status.busy": "2025-03-25T08:25:56.717543Z",
     "iopub.status.idle": "2025-03-25T08:25:56.804283Z",
     "shell.execute_reply": "2025-03-25T08:25:56.803993Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Background Information:\n",
      "!Series_title\t\"Molecular Prognosis of Cardiogenic Shock Patients under Extracorporeal Membrane Oxygenation\"\n",
      "!Series_summary\t\"Prognosis for cardiogenic shock patients under ECMO was our study goal. Success defined as survived more than 7 days after ECMO installation and failure died or had multiple organ failure in 7 days. Total 34 cases were enrolled, 17 success and 17 failure.\"\n",
      "!Series_summary\t\"Peripheral blood mononuclear cells collected at ECMO installation were used analyzed.\"\n",
      "!Series_overall_design\t\"Analysis of the cardiogenic shock patients at extracorporeal membrane oxygenation treatment by genome-wide expression and methylation. Transcriptomic profiling and DNA methylation between successful and failure groups were analyzed.\"\n",
      "!Series_overall_design\t\"This submission represents the transcriptome data.\"\n",
      "Sample Characteristics Dictionary:\n",
      "{0: ['course: Acute myocarditis', 'course: Acute myocardial infarction', 'course: Dilated cardiomyopathy, DCMP', 'course: Congestive heart failure', 'course: Dilated cardiomyopathy', 'course: Arrhythmia', 'course: Aortic dissection'], 1: ['age: 33.4', 'age: 51.2', 'age: 51.9', 'age: 47.8', 'age: 41.5', 'age: 67.3', 'age: 52.8', 'age: 16.1', 'age: 78.9', 'age: 53.2', 'age: 70.9', 'age: 59.9', 'age: 21.9', 'age: 45.2', 'age: 52.4', 'age: 32.3', 'age: 55.8', 'age: 47', 'age: 57.3', 'age: 31.7', 'age: 49.3', 'age: 66.1', 'age: 55.9', 'age: 49.1', 'age: 63', 'age: 21', 'age: 53.6', 'age: 50.1', 'age: 37.4', 'age: 71.5'], 2: ['gender: F', 'gender: M'], 3: ['outcome: Success', 'outcome: Failure', 'outcome: failure']}\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": "7add2ced",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "f8c921ed",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.805483Z",
     "iopub.status.busy": "2025-03-25T08:25:56.805381Z",
     "iopub.status.idle": "2025-03-25T08:25:56.815153Z",
     "shell.execute_reply": "2025-03-25T08:25:56.814866Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Preview of clinical features:\n",
      "{'GSM2443799': [0.0, 33.4, 0.0], 'GSM2443800': [0.0, 51.2, 1.0], 'GSM2443801': [0.0, 51.9, 0.0], 'GSM2443802': [0.0, 47.8, 1.0], 'GSM2443803': [0.0, 41.5, 0.0], 'GSM2443804': [0.0, 67.3, 1.0], 'GSM2443805': [0.0, 52.8, 1.0], 'GSM2443806': [0.0, 16.1, 1.0], 'GSM2443807': [0.0, 78.9, 1.0], 'GSM2443808': [0.0, 53.2, 1.0], 'GSM2443809': [0.0, 70.9, 1.0], 'GSM2443810': [0.0, 59.9, 1.0], 'GSM2443811': [0.0, 21.9, 0.0], 'GSM2443812': [1.0, 45.2, 0.0], 'GSM2443813': [0.0, 52.4, 1.0], 'GSM2443814': [0.0, 32.3, 1.0], 'GSM2443815': [0.0, 52.8, 1.0], 'GSM2443816': [0.0, 55.8, 1.0], 'GSM2443817': [0.0, 47.0, 1.0], 'GSM2443818': [0.0, 55.8, 1.0], 'GSM2443819': [0.0, 57.3, 0.0], 'GSM2443820': [0.0, 31.7, 0.0], 'GSM2443821': [0.0, 49.3, 1.0], 'GSM2443822': [1.0, 66.1, 1.0], 'GSM2443823': [0.0, 55.9, 1.0], 'GSM2443824': [0.0, 49.1, 0.0], 'GSM2443825': [0.0, 63.0, 1.0], 'GSM2443826': [0.0, 21.0, 1.0], 'GSM2443827': [0.0, 53.6, 1.0], 'GSM2443828': [0.0, 50.1, 0.0], 'GSM2443829': [0.0, 37.4, 1.0], 'GSM2443830': [0.0, 71.5, 0.0], 'GSM2443831': [1.0, 56.5, 1.0]}\n",
      "Clinical data saved to ../../output/preprocess/Congestive_heart_failure/clinical_data/GSE93101.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Gene Expression Data Availability\n",
    "# Based on the background information, this dataset contains transcriptome data\n",
    "# \"This submission represents the transcriptome data.\"\n",
    "is_gene_available = True\n",
    "\n",
    "# 2. Variable Availability and Data Type Conversion\n",
    "\n",
    "# 2.1 Data Availability\n",
    "\n",
    "# Trait: Congestive heart failure\n",
    "# Looking at the sample characteristics, key 0 contains \"course: Congestive heart failure\"\n",
    "# This suggests patients have different conditions, and we're interested in those with CHF\n",
    "trait_row = 0\n",
    "\n",
    "# Age: Available in key 1\n",
    "age_row = 1\n",
    "\n",
    "# Gender: Available in key 2\n",
    "gender_row = 2\n",
    "\n",
    "# 2.2 Data Type Conversion Functions\n",
    "\n",
    "def convert_trait(value):\n",
    "    \"\"\"Convert trait value to binary (0 or 1)\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        condition = value.split(\":\", 1)[1].strip()\n",
    "    else:\n",
    "        condition = value.strip()\n",
    "    \n",
    "    # Check if the condition is congestive heart failure (case insensitive)\n",
    "    if condition.lower() == \"congestive heart failure\":\n",
    "        return 1\n",
    "    else:\n",
    "        return 0\n",
    "\n",
    "def convert_age(value):\n",
    "    \"\"\"Convert age value to continuous (float)\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        age_str = value.split(\":\", 1)[1].strip()\n",
    "    else:\n",
    "        age_str = value.strip()\n",
    "    \n",
    "    try:\n",
    "        return float(age_str)\n",
    "    except (ValueError, TypeError):\n",
    "        return None\n",
    "\n",
    "def convert_gender(value):\n",
    "    \"\"\"Convert gender value to binary (0 for female, 1 for male)\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        gender = value.split(\":\", 1)[1].strip()\n",
    "    else:\n",
    "        gender = value.strip()\n",
    "    \n",
    "    if gender.upper() == \"F\":\n",
    "        return 0\n",
    "    elif gender.upper() == \"M\":\n",
    "        return 1\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "# Check if trait data is available (trait_row is not None)\n",
    "is_trait_available = trait_row is not None\n",
    "\n",
    "# Validate and save cohort info for initial filtering\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. Clinical Feature Extraction (if trait_row is not None)\n",
    "if trait_row is not None:\n",
    "    # Extract clinical features\n",
    "    clinical_features_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=convert_gender\n",
    "    )\n",
    "    \n",
    "    # Preview the extracted clinical features\n",
    "    preview = preview_df(clinical_features_df)\n",
    "    print(\"Preview of clinical features:\")\n",
    "    print(preview)\n",
    "    \n",
    "    # Save clinical data to CSV\n",
    "    os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)\n",
    "    clinical_features_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": "1fac0d62",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "1e627a09",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.816289Z",
     "iopub.status.busy": "2025-03-25T08:25:56.816191Z",
     "iopub.status.idle": "2025-03-25T08:25:56.940057Z",
     "shell.execute_reply": "2025-03-25T08:25:56.939619Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Matrix file found: ../../input/GEO/Congestive_heart_failure/GSE93101/GSE93101_series_matrix.txt.gz\n",
      "Gene data shape: (29363, 33)\n",
      "First 20 gene/probe identifiers:\n",
      "Index(['ILMN_1343291', 'ILMN_1651209', 'ILMN_1651228', 'ILMN_1651229',\n",
      "       'ILMN_1651235', 'ILMN_1651236', 'ILMN_1651237', 'ILMN_1651238',\n",
      "       'ILMN_1651254', 'ILMN_1651260', 'ILMN_1651262', 'ILMN_1651268',\n",
      "       'ILMN_1651278', 'ILMN_1651282', 'ILMN_1651285', 'ILMN_1651286',\n",
      "       'ILMN_1651292', 'ILMN_1651303', 'ILMN_1651309', 'ILMN_1651315'],\n",
      "      dtype='object', name='ID')\n"
     ]
    }
   ],
   "source": [
    "# 1. Get the SOFT and matrix file paths again \n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "print(f\"Matrix file found: {matrix_file}\")\n",
    "\n",
    "# 2. Use the get_genetic_data function from the library to get the gene_data\n",
    "try:\n",
    "    gene_data = get_genetic_data(matrix_file)\n",
    "    print(f\"Gene data shape: {gene_data.shape}\")\n",
    "    \n",
    "    # 3. Print the first 20 row IDs (gene or probe identifiers)\n",
    "    print(\"First 20 gene/probe identifiers:\")\n",
    "    print(gene_data.index[:20])\n",
    "except Exception as e:\n",
    "    print(f\"Error extracting gene data: {e}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "50eb9800",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "97245137",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.941465Z",
     "iopub.status.busy": "2025-03-25T08:25:56.941358Z",
     "iopub.status.idle": "2025-03-25T08:25:56.943231Z",
     "shell.execute_reply": "2025-03-25T08:25:56.942947Z"
    }
   },
   "outputs": [],
   "source": [
    "# The identifiers starting with \"ILMN_\" are Illumina probe IDs, not human gene symbols.\n",
    "# These are specific to Illumina microarray platforms and need to be mapped to standard gene symbols.\n",
    "# ILMN_ prefix indicates Illumina's proprietary probe identifiers from their microarray platforms.\n",
    "\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "49d4be7c",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "9dfc797f",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:25:56.944586Z",
     "iopub.status.busy": "2025-03-25T08:25:56.944487Z",
     "iopub.status.idle": "2025-03-25T08:26:07.851780Z",
     "shell.execute_reply": "2025-03-25T08:26:07.851336Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene annotation preview:\n",
      "Columns in gene annotation: ['ID', 'Transcript', 'Species', 'Source', 'Search_Key', 'ILMN_Gene', 'Source_Reference_ID', 'RefSeq_ID', 'Entrez_Gene_ID', 'GI', 'Accession', 'Symbol', 'Protein_Product', 'Array_Address_Id', 'Probe_Type', 'Probe_Start', 'SEQUENCE', 'Chromosome', 'Probe_Chr_Orientation', 'Probe_Coordinates', 'Cytoband', 'Definition', 'Ontology_Component', 'Ontology_Process', 'Ontology_Function', 'Synonyms', 'Obsolete_Probe_Id', 'GB_ACC']\n",
      "{'ID': ['ILMN_3166687', 'ILMN_3165566', 'ILMN_3164811', 'ILMN_3165363', 'ILMN_3166511'], 'Transcript': ['ILMN_333737', 'ILMN_333646', 'ILMN_333584', 'ILMN_333628', 'ILMN_333719'], 'Species': ['ILMN Controls', 'ILMN Controls', 'ILMN Controls', 'ILMN Controls', 'ILMN Controls'], 'Source': ['ILMN_Controls', 'ILMN_Controls', 'ILMN_Controls', 'ILMN_Controls', 'ILMN_Controls'], 'Search_Key': ['ERCC-00162', 'ERCC-00071', 'ERCC-00009', 'ERCC-00053', 'ERCC-00144'], 'ILMN_Gene': ['ERCC-00162', 'ERCC-00071', 'ERCC-00009', 'ERCC-00053', 'ERCC-00144'], 'Source_Reference_ID': ['ERCC-00162', 'ERCC-00071', 'ERCC-00009', 'ERCC-00053', 'ERCC-00144'], 'RefSeq_ID': [nan, nan, nan, nan, nan], 'Entrez_Gene_ID': [nan, nan, nan, nan, nan], 'GI': [nan, nan, nan, nan, nan], 'Accession': ['DQ516750', 'DQ883654', 'DQ668364', 'DQ516785', 'DQ854995'], 'Symbol': ['ERCC-00162', 'ERCC-00071', 'ERCC-00009', 'ERCC-00053', 'ERCC-00144'], 'Protein_Product': [nan, nan, nan, nan, nan], 'Array_Address_Id': [5270161.0, 4260594.0, 7610424.0, 5260356.0, 2030196.0], 'Probe_Type': ['S', 'S', 'S', 'S', 'S'], 'Probe_Start': [12.0, 224.0, 868.0, 873.0, 130.0], 'SEQUENCE': ['CCCATGTGTCCAATTCTGAATATCTTTCCAGCTAAGTGCTTCTGCCCACC', 'GGATTAACTGCTGTGGTGTGTCATACTCGGCTACCTCCTGGTTTGGCGTC', 'GACCACGCCTTGTAATCGTATGACACGCGCTTGACACGACTGAATCCAGC', 'CTGCAATGCCATTAACAACCTTAGCACGGTATTTCCAGTAGCTGGTGAGC', 'CGTGCAGACAGGGATCGTAAGGCGATCCAGCCGGTATACCTTAGTCACAT'], 'Chromosome': [nan, nan, nan, nan, nan], 'Probe_Chr_Orientation': [nan, nan, nan, nan, nan], 'Probe_Coordinates': [nan, nan, nan, nan, nan], 'Cytoband': [nan, nan, nan, nan, nan], 'Definition': ['Methanocaldococcus jannaschii spike-in control MJ-500-33 genomic sequence', 'Synthetic construct clone NISTag13 external RNA control sequence', 'Synthetic construct clone TagJ microarray control', 'Methanocaldococcus jannaschii spike-in control MJ-1000-68 genomic sequence', 'Synthetic construct clone AG006.1100 external RNA control sequence'], 'Ontology_Component': [nan, nan, nan, nan, nan], 'Ontology_Process': [nan, nan, nan, nan, nan], 'Ontology_Function': [nan, nan, nan, nan, nan], 'Synonyms': [nan, nan, nan, nan, nan], 'Obsolete_Probe_Id': [nan, nan, nan, nan, nan], 'GB_ACC': ['DQ516750', 'DQ883654', 'DQ668364', 'DQ516785', 'DQ854995']}\n",
      "\n",
      "Analyzing SPOT_ID.1 column for gene symbols:\n",
      "\n",
      "Gene data ID prefix: ILMN\n",
      "Column 'ID' contains values matching gene data ID pattern\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Column 'Transcript' contains values matching gene data ID pattern\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Column 'Species' contains values matching gene data ID pattern\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Column 'Source' contains values matching gene data ID pattern\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Checking for columns containing transcript or gene related terms:\n",
      "Column 'Transcript' may contain gene-related information\n",
      "Sample values: ['ILMN_333737', 'ILMN_333646', 'ILMN_333584']\n",
      "Column 'ILMN_Gene' may contain gene-related information\n",
      "Sample values: ['ERCC-00162', 'ERCC-00071', 'ERCC-00009']\n",
      "Column 'Entrez_Gene_ID' may contain gene-related information\n",
      "Sample values: [nan, nan, nan]\n",
      "Column 'Symbol' may contain gene-related information\n",
      "Sample values: ['ERCC-00162', 'ERCC-00071', 'ERCC-00009']\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. Analyze the gene annotation dataframe to identify which columns contain the gene identifiers and gene symbols\n",
    "print(\"\\nGene annotation preview:\")\n",
    "print(f\"Columns in gene annotation: {gene_annotation.columns.tolist()}\")\n",
    "print(preview_df(gene_annotation, n=5))\n",
    "\n",
    "# Check for gene information in the SPOT_ID.1 column which appears to contain gene names\n",
    "print(\"\\nAnalyzing SPOT_ID.1 column for gene symbols:\")\n",
    "if 'SPOT_ID.1' in gene_annotation.columns:\n",
    "    # Extract a few sample values\n",
    "    sample_values = gene_annotation['SPOT_ID.1'].head(3).tolist()\n",
    "    for i, value in enumerate(sample_values):\n",
    "        print(f\"Sample {i+1} excerpt: {value[:200]}...\")  # Print first 200 chars\n",
    "        # Test the extract_human_gene_symbols function on these values\n",
    "        symbols = extract_human_gene_symbols(value)\n",
    "        print(f\"  Extracted gene symbols: {symbols}\")\n",
    "\n",
    "# Try to find the probe IDs in the gene annotation\n",
    "gene_data_id_prefix = gene_data.index[0].split('_')[0]  # Get prefix of first gene ID\n",
    "print(f\"\\nGene data ID prefix: {gene_data_id_prefix}\")\n",
    "\n",
    "# Look for columns that might match the gene data IDs\n",
    "for col in gene_annotation.columns:\n",
    "    if gene_annotation[col].astype(str).str.contains(gene_data_id_prefix).any():\n",
    "        print(f\"Column '{col}' contains values matching gene data ID pattern\")\n",
    "\n",
    "# Check if there's any column that might contain transcript or gene IDs\n",
    "print(\"\\nChecking for columns containing transcript or gene related terms:\")\n",
    "for col in gene_annotation.columns:\n",
    "    if any(term in col.upper() for term in ['GENE', 'TRANSCRIPT', 'SYMBOL', 'NAME', 'DESCRIPTION']):\n",
    "        print(f\"Column '{col}' may contain gene-related information\")\n",
    "        # Show sample values\n",
    "        print(f\"Sample values: {gene_annotation[col].head(3).tolist()}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "57195f28",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "4fd8c11e",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:26:07.853300Z",
     "iopub.status.busy": "2025-03-25T08:26:07.853179Z",
     "iopub.status.idle": "2025-03-25T08:26:08.030849Z",
     "shell.execute_reply": "2025-03-25T08:26:08.030477Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene mapping preview:\n",
      "Gene mapping shape: (29377, 2)\n",
      "{'ID': ['ILMN_3166687', 'ILMN_3165566', 'ILMN_3164811', 'ILMN_3165363', 'ILMN_3166511'], 'Gene': ['ERCC-00162', 'ERCC-00071', 'ERCC-00009', 'ERCC-00053', 'ERCC-00144']}\n",
      "\n",
      "Gene expression data after mapping:\n",
      "Shape: (20206, 33)\n",
      "First 5 gene symbols: ['A1BG', 'A1CF', 'A26C3', 'A2BP1', 'A2LD1']\n",
      "Number of unique gene symbols: 20206\n",
      "Common genes found: ['TP53', 'BRCA1', 'EGFR', 'TNF', 'IL6']\n"
     ]
    }
   ],
   "source": [
    "# 1. Based on the preview, we can see that:\n",
    "# - 'ID' column in the gene annotation contains the same ILMN_ identifiers used in gene expression data\n",
    "# - 'Symbol' column contains gene symbols we need to map to\n",
    "\n",
    "# 2. Get gene mapping dataframe using the function from the library\n",
    "gene_mapping = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='Symbol')\n",
    "\n",
    "# Examine the mapping to verify it has the expected format\n",
    "print(\"\\nGene mapping preview:\")\n",
    "print(f\"Gene mapping shape: {gene_mapping.shape}\")\n",
    "print(preview_df(gene_mapping, n=5))\n",
    "\n",
    "# 3. Apply gene mapping to convert probe-level expression to gene-level expression\n",
    "gene_data = apply_gene_mapping(gene_data, gene_mapping)\n",
    "\n",
    "# Preview the resulting gene expression data\n",
    "print(\"\\nGene expression data after mapping:\")\n",
    "print(f\"Shape: {gene_data.shape}\")\n",
    "print(f\"First 5 gene symbols: {gene_data.index[:5].tolist()}\")\n",
    "\n",
    "# Examine number of unique gene symbols\n",
    "print(f\"Number of unique gene symbols: {len(gene_data.index.unique())}\")\n",
    "\n",
    "# Check if standard gene symbols are present by looking for common genes\n",
    "common_genes = [\"TP53\", \"BRCA1\", \"EGFR\", \"TNF\", \"IL6\"]\n",
    "found_genes = [gene for gene in common_genes if gene in gene_data.index]\n",
    "print(f\"Common genes found: {found_genes}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "a23bc703",
   "metadata": {},
   "source": [
    "### Step 7: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "24420a29",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:26:08.032641Z",
     "iopub.status.busy": "2025-03-25T08:26:08.032528Z",
     "iopub.status.idle": "2025-03-25T08:26:14.377772Z",
     "shell.execute_reply": "2025-03-25T08:26:14.377224Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene data shape before normalization: (20206, 33)\n",
      "Gene data shape after normalization: (19445, 33)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalized gene expression data saved to ../../output/preprocess/Congestive_heart_failure/gene_data/GSE93101.csv\n",
      "Original clinical data preview:\n",
      "         !Sample_geo_accession                 GSM2443799  \\\n",
      "0  !Sample_characteristics_ch1  course: Acute myocarditis   \n",
      "1  !Sample_characteristics_ch1                  age: 33.4   \n",
      "2  !Sample_characteristics_ch1                  gender: F   \n",
      "3  !Sample_characteristics_ch1           outcome: Success   \n",
      "\n",
      "                  GSM2443800                 GSM2443801  \\\n",
      "0  course: Acute myocarditis  course: Acute myocarditis   \n",
      "1                  age: 51.2                  age: 51.9   \n",
      "2                  gender: M                  gender: F   \n",
      "3           outcome: Success           outcome: Failure   \n",
      "\n",
      "                            GSM2443802                 GSM2443803  \\\n",
      "0  course: Acute myocardial infarction  course: Acute myocarditis   \n",
      "1                            age: 47.8                  age: 41.5   \n",
      "2                            gender: M                  gender: F   \n",
      "3                     outcome: Success           outcome: Failure   \n",
      "\n",
      "                            GSM2443804                           GSM2443805  \\\n",
      "0  course: Acute myocardial infarction  course: Acute myocardial infarction   \n",
      "1                            age: 67.3                            age: 52.8   \n",
      "2                            gender: M                            gender: M   \n",
      "3                     outcome: Failure                     outcome: Success   \n",
      "\n",
      "                             GSM2443806                           GSM2443807  \\\n",
      "0  course: Dilated cardiomyopathy, DCMP  course: Acute myocardial infarction   \n",
      "1                             age: 16.1                            age: 78.9   \n",
      "2                             gender: M                            gender: M   \n",
      "3                      outcome: Failure                     outcome: Failure   \n",
      "\n",
      "   ...                        GSM2443822                 GSM2443823  \\\n",
      "0  ...  course: Congestive heart failure  course: Aortic dissection   \n",
      "1  ...                         age: 66.1                  age: 55.9   \n",
      "2  ...                         gender: M                  gender: M   \n",
      "3  ...                  outcome: Success           outcome: Failure   \n",
      "\n",
      "                             GSM2443824                           GSM2443825  \\\n",
      "0  course: Dilated cardiomyopathy, DCMP  course: Acute myocardial infarction   \n",
      "1                             age: 49.1                              age: 63   \n",
      "2                             gender: F                            gender: M   \n",
      "3                      outcome: Failure                     outcome: Failure   \n",
      "\n",
      "                             GSM2443826                           GSM2443827  \\\n",
      "0  course: Dilated cardiomyopathy, DCMP  course: Acute myocardial infarction   \n",
      "1                               age: 21                            age: 53.6   \n",
      "2                             gender: M                            gender: M   \n",
      "3                      outcome: Failure                     outcome: Success   \n",
      "\n",
      "                            GSM2443828                           GSM2443829  \\\n",
      "0  course: Acute myocardial infarction  course: Acute myocardial infarction   \n",
      "1                            age: 50.1                            age: 37.4   \n",
      "2                            gender: F                            gender: M   \n",
      "3                     outcome: Success                     outcome: Failure   \n",
      "\n",
      "                  GSM2443830                        GSM2443831  \n",
      "0  course: Acute myocarditis  course: Congestive heart failure  \n",
      "1                  age: 71.5                         age: 56.5  \n",
      "2                  gender: F                         gender: M  \n",
      "3           outcome: Success                  outcome: Success  \n",
      "\n",
      "[4 rows x 34 columns]\n",
      "Selected clinical data shape: (3, 33)\n",
      "Clinical data preview:\n",
      "                          GSM2443799  GSM2443800  GSM2443801  GSM2443802  \\\n",
      "Congestive_heart_failure         0.0         0.0         0.0         0.0   \n",
      "Age                             33.4        51.2        51.9        47.8   \n",
      "Gender                           0.0         1.0         0.0         1.0   \n",
      "\n",
      "                          GSM2443803  GSM2443804  GSM2443805  GSM2443806  \\\n",
      "Congestive_heart_failure         0.0         0.0         0.0         0.0   \n",
      "Age                             41.5        67.3        52.8        16.1   \n",
      "Gender                           0.0         1.0         1.0         1.0   \n",
      "\n",
      "                          GSM2443807  GSM2443808  ...  GSM2443822  GSM2443823  \\\n",
      "Congestive_heart_failure         0.0         0.0  ...         1.0         0.0   \n",
      "Age                             78.9        53.2  ...        66.1        55.9   \n",
      "Gender                           1.0         1.0  ...         1.0         1.0   \n",
      "\n",
      "                          GSM2443824  GSM2443825  GSM2443826  GSM2443827  \\\n",
      "Congestive_heart_failure         0.0         0.0         0.0         0.0   \n",
      "Age                             49.1        63.0        21.0        53.6   \n",
      "Gender                           0.0         1.0         1.0         1.0   \n",
      "\n",
      "                          GSM2443828  GSM2443829  GSM2443830  GSM2443831  \n",
      "Congestive_heart_failure         0.0         0.0         0.0         1.0  \n",
      "Age                             50.1        37.4        71.5        56.5  \n",
      "Gender                           0.0         1.0         0.0         1.0  \n",
      "\n",
      "[3 rows x 33 columns]\n",
      "Linked data shape before processing: (33, 19448)\n",
      "Linked data preview (first 5 rows, 5 columns):\n",
      "            Congestive_heart_failure   Age  Gender        A1BG     A1BG-AS1\n",
      "GSM2443799                       0.0  33.4     0.0  129.442547  1330.542639\n",
      "GSM2443800                       0.0  51.2     1.0  142.061233  2177.610030\n",
      "GSM2443801                       0.0  51.9     0.0  103.958331  1130.866630\n",
      "GSM2443802                       0.0  47.8     1.0  137.556161  1116.450458\n",
      "GSM2443803                       0.0  41.5     0.0  111.260768  1112.964973\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Data shape after handling missing values: (33, 19448)\n",
      "For the feature 'Congestive_heart_failure', the least common label is '1.0' with 3 occurrences. This represents 9.09% of the dataset.\n",
      "Quartiles for 'Age':\n",
      "  25%: 45.2\n",
      "  50% (Median): 52.4\n",
      "  75%: 56.5\n",
      "Min: 16.1\n",
      "Max: 78.9\n",
      "For the feature 'Gender', the least common label is '0.0' with 10 occurrences. This represents 30.30% of the dataset.\n",
      "Dataset is not usable for analysis. No linked data file saved.\n"
     ]
    }
   ],
   "source": [
    "# 1. Normalize gene symbols in the gene expression data\n",
    "# Use normalize_gene_symbols_in_index to standardize gene symbols\n",
    "normalized_gene_data = normalize_gene_symbols_in_index(gene_data)\n",
    "print(f\"Gene data shape before normalization: {gene_data.shape}\")\n",
    "print(f\"Gene data shape after normalization: {normalized_gene_data.shape}\")\n",
    "\n",
    "# Save the normalized gene data to file\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 expression data saved to {out_gene_data_file}\")\n",
    "\n",
    "# Load the actual clinical data from the matrix file that was previously obtained in Step 1\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "background_info, clinical_data = get_background_and_clinical_data(matrix_file)\n",
    "\n",
    "# Get preview of clinical data to understand its structure\n",
    "print(\"Original clinical data preview:\")\n",
    "print(clinical_data.head())\n",
    "\n",
    "# 2. If we have trait data available, proceed with linking\n",
    "if trait_row is not None:\n",
    "    # Extract clinical features using the original clinical data\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=convert_gender\n",
    "    )\n",
    "\n",
    "    print(f\"Selected clinical data shape: {selected_clinical_df.shape}\")\n",
    "    print(\"Clinical data preview:\")\n",
    "    print(selected_clinical_df.head())\n",
    "\n",
    "    # Link the clinical and genetic data\n",
    "    linked_data = geo_link_clinical_genetic_data(selected_clinical_df, normalized_gene_data)\n",
    "    print(f\"Linked data shape before processing: {linked_data.shape}\")\n",
    "    print(\"Linked data preview (first 5 rows, 5 columns):\")\n",
    "    print(linked_data.iloc[:5, :5] if not linked_data.empty else \"Empty dataframe\")\n",
    "\n",
    "    # 3. Handle missing values\n",
    "    try:\n",
    "        linked_data = handle_missing_values(linked_data, trait)\n",
    "        print(f\"Data shape after handling missing values: {linked_data.shape}\")\n",
    "    except Exception as e:\n",
    "        print(f\"Error handling missing values: {e}\")\n",
    "        linked_data = pd.DataFrame()  # Create empty dataframe if error occurs\n",
    "\n",
    "    # 4. Check for bias in features\n",
    "    if not linked_data.empty and linked_data.shape[0] > 0:\n",
    "        # Check if trait is biased\n",
    "        trait_type = 'binary' if len(linked_data[trait].unique()) <= 2 else 'continuous'\n",
    "        if trait_type == \"binary\":\n",
    "            is_biased = judge_binary_variable_biased(linked_data, trait)\n",
    "        else:\n",
    "            is_biased = judge_continuous_variable_biased(linked_data, trait)\n",
    "            \n",
    "        # Remove biased demographic features\n",
    "        if \"Age\" in linked_data.columns:\n",
    "            age_biased = judge_continuous_variable_biased(linked_data, 'Age')\n",
    "            if age_biased:\n",
    "                linked_data = linked_data.drop(columns='Age')\n",
    "                \n",
    "        if \"Gender\" in linked_data.columns:\n",
    "            gender_biased = judge_binary_variable_biased(linked_data, 'Gender')\n",
    "            if gender_biased:\n",
    "                linked_data = linked_data.drop(columns='Gender')\n",
    "    else:\n",
    "        is_biased = True\n",
    "        print(\"Cannot check for bias as dataframe is empty or has no rows after missing value handling\")\n",
    "\n",
    "    # 5. Validate and save cohort information\n",
    "    note = \"\"\n",
    "    if linked_data.empty or linked_data.shape[0] == 0:\n",
    "        note = \"Dataset contains gene expression data related to atrial fibrillation after cardiac surgery, but linking clinical and genetic data failed, possibly due to mismatched sample IDs.\"\n",
    "    else:\n",
    "        note = \"Dataset contains gene expression data for atrial fibrillation after cardiac surgery, which is relevant to arrhythmia research.\"\n",
    "    \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_biased,\n",
    "        df=linked_data,\n",
    "        note=note\n",
    "    )\n",
    "\n",
    "    # 6. Save the linked data if usable\n",
    "    if is_usable:\n",
    "        os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n",
    "        linked_data.to_csv(out_data_file)\n",
    "        print(f\"Linked data saved to {out_data_file}\")\n",
    "    else:\n",
    "        print(\"Dataset is not usable for analysis. No linked data file saved.\")\n",
    "else:\n",
    "    # If no trait data available, validate with trait_available=False\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=False,\n",
    "        is_biased=True,  # Set to True since we can't use data without trait\n",
    "        df=pd.DataFrame(),  # Empty DataFrame\n",
    "        note=\"Dataset contains gene expression data but lacks proper clinical trait information for arrhythmia analysis.\"\n",
    "    )\n",
    "    \n",
    "    print(\"Dataset is not usable for arrhythmia analysis due to lack of clinical trait data. No linked data file saved.\")"
   ]
  }
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