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{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "889b6fb9",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.303508Z",
     "iopub.status.busy": "2025-03-25T06:38:14.303270Z",
     "iopub.status.idle": "2025-03-25T06:38:14.468510Z",
     "shell.execute_reply": "2025-03-25T06:38:14.468079Z"
    }
   },
   "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 = \"Arrhythmia\"\n",
    "cohort = \"GSE93101\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Arrhythmia\"\n",
    "in_cohort_dir = \"../../input/GEO/Arrhythmia/GSE93101\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Arrhythmia/GSE93101.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Arrhythmia/gene_data/GSE93101.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Arrhythmia/clinical_data/GSE93101.csv\"\n",
    "json_path = \"../../output/preprocess/Arrhythmia/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "23c4de08",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "762dab80",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.469794Z",
     "iopub.status.busy": "2025-03-25T06:38:14.469653Z",
     "iopub.status.idle": "2025-03-25T06:38:14.557086Z",
     "shell.execute_reply": "2025-03-25T06:38:14.556597Z"
    }
   },
   "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": "a304d5e6",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "6bdd38ca",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.558621Z",
     "iopub.status.busy": "2025-03-25T06:38:14.558509Z",
     "iopub.status.idle": "2025-03-25T06:38:14.563763Z",
     "shell.execute_reply": "2025-03-25T06:38:14.563314Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Cannot extract clinical features: clinical data matrix not available\n",
      "The sample characteristics dictionary only provides possible values, not sample-specific data\n",
      "Clinical data extraction skipped due to missing proper clinical data matrix format.\n"
     ]
    }
   ],
   "source": [
    "import pandas as pd\n",
    "import os\n",
    "from typing import Optional, Dict, Any, Callable\n",
    "import json\n",
    "\n",
    "# Set variables based on analysis\n",
    "is_gene_available = True  # The dataset appears to contain gene expression data based on the Series_overall_design\n",
    "\n",
    "# 2.1 Data Availability\n",
    "# Based on the sample characteristics dictionary:\n",
    "trait_row = 0  # Course of disease (contains Arrhythmia)\n",
    "age_row = 1    # Age information\n",
    "gender_row = 2 # Gender information\n",
    "\n",
    "# 2.2 Data Type Conversion Functions\n",
    "def convert_trait(value: str) -> int:\n",
    "    \"\"\"Convert trait value to binary (0 or 1).\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    # Extract the value after the colon and strip whitespace\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    # Check if \"Arrhythmia\" is in the value\n",
    "    return 1 if \"Arrhythmia\" in value else 0\n",
    "\n",
    "def convert_age(value: str) -> float:\n",
    "    \"\"\"Convert age value to continuous float.\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    # Extract the value after the colon and strip whitespace\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    try:\n",
    "        return float(value)\n",
    "    except (ValueError, TypeError):\n",
    "        return None\n",
    "\n",
    "def convert_gender(value: str) -> int:\n",
    "    \"\"\"Convert gender value to binary (0 for female, 1 for male).\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    # Extract the value after the colon and strip whitespace\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    if value.upper() == 'F':\n",
    "        return 0\n",
    "    elif value.upper() == 'M':\n",
    "        return 1\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "is_trait_available = trait_row is not None\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\n",
    "if trait_row is not None:\n",
    "    try:\n",
    "        # Since we don't have the actual clinical data matrix and cannot create one from the\n",
    "        # sample characteristics dictionary directly, we'll skip this step for now\n",
    "        print(\"Cannot extract clinical features: clinical data matrix not available\")\n",
    "        print(\"The sample characteristics dictionary only provides possible values, not sample-specific data\")\n",
    "        \n",
    "        # Create a note about this dataset\n",
    "        note = \"Clinical data extraction skipped due to missing proper clinical data matrix format.\"\n",
    "        print(note)\n",
    "    except Exception as e:\n",
    "        print(f\"Error processing clinical data: {e}\")\n",
    "else:\n",
    "    print(\"Clinical data not available. Skipping clinical feature extraction.\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ebb9c0ce",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "a98817f4",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.565213Z",
     "iopub.status.busy": "2025-03-25T06:38:14.565107Z",
     "iopub.status.idle": "2025-03-25T06:38:14.688631Z",
     "shell.execute_reply": "2025-03-25T06:38:14.688125Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Matrix file found: ../../input/GEO/Arrhythmia/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": "74948b52",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "0db0c762",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.689770Z",
     "iopub.status.busy": "2025-03-25T06:38:14.689655Z",
     "iopub.status.idle": "2025-03-25T06:38:14.691676Z",
     "shell.execute_reply": "2025-03-25T06:38:14.691338Z"
    }
   },
   "outputs": [],
   "source": [
    "# Analyzing the gene identifiers from the previous step\n",
    "\n",
    "# The identifiers start with \"ILMN_\" which indicates they are Illumina probe IDs\n",
    "# Illumina probe IDs are not human gene symbols, they need to be mapped to gene symbols\n",
    "# These are likely from an Illumina BeadArray microarray platform\n",
    "\n",
    "# Therefore, gene mapping is required\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "fa8273b4",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "bedb2310",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:14.692685Z",
     "iopub.status.busy": "2025-03-25T06:38:14.692581Z",
     "iopub.status.idle": "2025-03-25T06:38:25.677024Z",
     "shell.execute_reply": "2025-03-25T06:38:25.676520Z"
    }
   },
   "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": "debd03f9",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "8658340f",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:25.678943Z",
     "iopub.status.busy": "2025-03-25T06:38:25.678819Z",
     "iopub.status.idle": "2025-03-25T06:38:26.269667Z",
     "shell.execute_reply": "2025-03-25T06:38:26.269133Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene mapping dataframe shape: (29377, 2)\n",
      "First few rows of mapping dataframe:\n",
      "             ID        Gene\n",
      "0  ILMN_3166687  ERCC-00162\n",
      "1  ILMN_3165566  ERCC-00071\n",
      "2  ILMN_3164811  ERCC-00009\n",
      "3  ILMN_3165363  ERCC-00053\n",
      "4  ILMN_3166511  ERCC-00144\n",
      "\n",
      "Gene expression dataframe shape: (20206, 33)\n",
      "First few rows of gene expression dataframe:\n",
      "       GSM2443799  GSM2443800   GSM2443801  GSM2443802   GSM2443803  \\\n",
      "Gene                                                                  \n",
      "A1BG   129.442547  142.061233   103.958331  137.556161   111.260768   \n",
      "A1CF   460.835089  324.958428   484.608278  683.954295   657.945539   \n",
      "A26C3  117.769485   96.247228   143.474170  113.274705   111.123349   \n",
      "A2BP1  445.728633  419.931068  1118.462328  882.773847   455.880246   \n",
      "A2LD1  726.498733  129.188312   273.126915  724.925706  1183.148561   \n",
      "\n",
      "       GSM2443804  GSM2443805  GSM2443806   GSM2443807  GSM2443808  ...  \\\n",
      "Gene                                                                ...   \n",
      "A1BG   241.767585  157.977946  147.578249   113.936195  161.539471  ...   \n",
      "A1CF   483.623025  388.058988  347.761757   846.802093  348.534342  ...   \n",
      "A26C3  189.907418  121.229217  180.446535   114.821849  146.988180  ...   \n",
      "A2BP1  629.064099  482.388074  472.663155   673.371186  451.317487  ...   \n",
      "A2LD1  831.739064  430.191854  980.267191  1435.172976  438.148076  ...   \n",
      "\n",
      "       GSM2443822   GSM2443823  GSM2443824  GSM2443825  GSM2443826  \\\n",
      "Gene                                                                 \n",
      "A1BG   117.848741   124.533076  132.452962  144.929004  187.460276   \n",
      "A1CF   369.897346  1241.655372  318.911691  281.418179  331.841325   \n",
      "A26C3  179.599911   149.774005   97.226031  120.221383  168.306395   \n",
      "A2BP1  401.373193   480.150197  447.940559  404.073618  485.758301   \n",
      "A2LD1  387.785812   675.875024  345.430061  840.092985  251.316867   \n",
      "\n",
      "        GSM2443827  GSM2443828  GSM2443829  GSM2443830  GSM2443831  \n",
      "Gene                                                                \n",
      "A1BG    146.166922  170.230229  158.397937  160.564160  164.299385  \n",
      "A1CF    328.965408  349.474755  815.252732  290.193532  293.717875  \n",
      "A26C3   150.220434  107.689969  112.205759  132.270634  131.737339  \n",
      "A2BP1   461.588680  373.266036  396.053696  410.223933  427.722595  \n",
      "A2LD1  1059.292255  755.505991  415.081233  702.809967  649.972564  \n",
      "\n",
      "[5 rows x 33 columns]\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene expression data saved to ../../output/preprocess/Arrhythmia/gene_data/GSE93101.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Identify the columns for gene identifiers and gene symbols\n",
    "# From the previous output, we can see:\n",
    "# - 'ID' column contains the probe IDs (ILMN_*)\n",
    "# - 'Symbol' column contains gene symbols\n",
    "\n",
    "# 2. Create the gene mapping dataframe\n",
    "mapping_df = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='Symbol')\n",
    "print(f\"Gene mapping dataframe shape: {mapping_df.shape}\")\n",
    "print(\"First few rows of mapping dataframe:\")\n",
    "print(mapping_df.head())\n",
    "\n",
    "# 3. Apply the gene mapping to convert probe-level data to gene-level data\n",
    "gene_data = apply_gene_mapping(gene_data, mapping_df)\n",
    "\n",
    "# Show the first few rows of the gene expression dataframe\n",
    "print(f\"\\nGene expression dataframe shape: {gene_data.shape}\")\n",
    "print(\"First few rows of gene expression dataframe:\")\n",
    "print(gene_data.head())\n",
    "\n",
    "# Save the gene expression data to CSV\n",
    "os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "gene_data.to_csv(out_gene_data_file)\n",
    "print(f\"\\nGene expression data saved to {out_gene_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "89be3833",
   "metadata": {},
   "source": [
    "### Step 7: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "7a51c83c",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:38:26.271463Z",
     "iopub.status.busy": "2025-03-25T06:38:26.271338Z",
     "iopub.status.idle": "2025-03-25T06:38:32.503432Z",
     "shell.execute_reply": "2025-03-25T06:38:32.503085Z"
    }
   },
   "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/Arrhythmia/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  GSM2443803  \\\n",
      "Arrhythmia         0.0         0.0         0.0         0.0         0.0   \n",
      "Age               33.4        51.2        51.9        47.8        41.5   \n",
      "Gender             0.0         1.0         0.0         1.0         0.0   \n",
      "\n",
      "            GSM2443804  GSM2443805  GSM2443806  GSM2443807  GSM2443808  ...  \\\n",
      "Arrhythmia         0.0         0.0         0.0         0.0         0.0  ...   \n",
      "Age               67.3        52.8        16.1        78.9        53.2  ...   \n",
      "Gender             1.0         1.0         1.0         1.0         1.0  ...   \n",
      "\n",
      "            GSM2443822  GSM2443823  GSM2443824  GSM2443825  GSM2443826  \\\n",
      "Arrhythmia         0.0         0.0         0.0         0.0         0.0   \n",
      "Age               66.1        55.9        49.1        63.0        21.0   \n",
      "Gender             1.0         1.0         0.0         1.0         1.0   \n",
      "\n",
      "            GSM2443827  GSM2443828  GSM2443829  GSM2443830  GSM2443831  \n",
      "Arrhythmia         0.0         0.0         0.0         0.0         0.0  \n",
      "Age               53.6        50.1        37.4        71.5        56.5  \n",
      "Gender             1.0         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",
      "            Arrhythmia   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 'Arrhythmia', the least common label is '1.0' with 2 occurrences. This represents 6.06% of the dataset.\n",
      "The distribution of the feature 'Arrhythmia' in this dataset is severely biased.\n",
      "\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",
      "The distribution of the feature 'Age' in this dataset is fine.\n",
      "\n",
      "For the feature 'Gender', the least common label is '0.0' with 10 occurrences. This represents 30.30% of the dataset.\n",
      "The distribution of the feature 'Gender' in this dataset is fine.\n",
      "\n",
      "Data shape after removing biased features: (33, 19448)\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",
    "        is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)\n",
    "        print(f\"Data shape after removing biased features: {linked_data.shape}\")\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 liver fibrosis progression, but linking clinical and genetic data failed, possibly due to mismatched sample IDs.\"\n",
    "    else:\n",
    "        note = \"Dataset contains gene expression data for liver fibrosis progression, which is relevant to liver cirrhosis 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 liver cirrhosis analysis.\"\n",
    "    )\n",
    "    \n",
    "    print(\"Dataset is not usable for liver cirrhosis analysis due to lack of clinical trait data. No linked data file saved.\")"
   ]
  }
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