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{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "fc9e2c8c",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:12.743629Z",
     "iopub.status.busy": "2025-03-25T03:43:12.743522Z",
     "iopub.status.idle": "2025-03-25T03:43:12.919675Z",
     "shell.execute_reply": "2025-03-25T03:43:12.919298Z"
    }
   },
   "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 = \"Psoriasis\"\n",
    "cohort = \"GSE183134\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Psoriasis\"\n",
    "in_cohort_dir = \"../../input/GEO/Psoriasis/GSE183134\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Psoriasis/GSE183134.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Psoriasis/gene_data/GSE183134.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Psoriasis/clinical_data/GSE183134.csv\"\n",
    "json_path = \"../../output/preprocess/Psoriasis/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "53975da2",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "22e803eb",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:12.921238Z",
     "iopub.status.busy": "2025-03-25T03:43:12.921076Z",
     "iopub.status.idle": "2025-03-25T03:43:13.026969Z",
     "shell.execute_reply": "2025-03-25T03:43:13.026605Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Background Information:\n",
      "!Series_title\t\"Transcriptomic profiling of Pityriasis Rubra Pilaris (PRP) and Psoriasis\"\n",
      "!Series_summary\t\"The microarray experiment was employed to evaluate the gene expressions in skin lesions of PRP and psoriasis.\"\n",
      "!Series_overall_design\t\"To investigate the specific gene regulations, microarray profiling was performed on RNA extracted from paraffin embedded skin biopsy samples.\"\n",
      "Sample Characteristics Dictionary:\n",
      "{0: ['tissue: Skin'], 1: ['disease state: Pityriasis_Rubra_Pilaris', 'disease state: Psoriasis']}\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": "938c9e97",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "2857c024",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:13.028247Z",
     "iopub.status.busy": "2025-03-25T03:43:13.028130Z",
     "iopub.status.idle": "2025-03-25T03:43:13.036019Z",
     "shell.execute_reply": "2025-03-25T03:43:13.035681Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Preview of selected clinical features:\n",
      "{'GSM5551681': [0.0], 'GSM5551682': [0.0], 'GSM5551683': [0.0], 'GSM5551684': [0.0], 'GSM5551685': [0.0], 'GSM5551686': [0.0], 'GSM5551687': [0.0], 'GSM5551688': [0.0], 'GSM5551689': [0.0], 'GSM5551690': [0.0], 'GSM5551691': [0.0], 'GSM5551692': [0.0], 'GSM5551693': [0.0], 'GSM5551694': [1.0], 'GSM5551695': [1.0], 'GSM5551696': [1.0], 'GSM5551697': [1.0], 'GSM5551698': [1.0], 'GSM5551699': [1.0], 'GSM5551700': [1.0], 'GSM5551701': [1.0], 'GSM5551702': [1.0], 'GSM5551703': [1.0], 'GSM5551704': [1.0], 'GSM5551705': [1.0], 'GSM5551706': [1.0], 'GSM5551707': [1.0], 'GSM5551708': [1.0], 'GSM5551709': [1.0], 'GSM5551710': [1.0], 'GSM5551711': [1.0], 'GSM5551712': [1.0], 'GSM5551713': [1.0], 'GSM5551714': [1.0], 'GSM5551715': [1.0]}\n",
      "Clinical data saved to ../../output/preprocess/Psoriasis/clinical_data/GSE183134.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Gene Expression Data Availability\n",
    "# Based on the background information, this is a microarray profiling study,\n",
    "# so it likely contains gene expression data\n",
    "is_gene_available = True\n",
    "\n",
    "# 2. Variable Availability and Data Type Conversion\n",
    "# 2.1 Data Availability\n",
    "# Checking the Sample Characteristics Dictionary\n",
    "# The trait data (disease state) is available in row 1\n",
    "trait_row = 1\n",
    "# No age information is available\n",
    "age_row = None\n",
    "# No gender information is available\n",
    "gender_row = None\n",
    "\n",
    "# 2.2 Data Type Conversion\n",
    "def convert_trait(value):\n",
    "    \"\"\"Convert trait value to binary format (0 for PRP, 1 for Psoriasis)\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    # Extract the value part if it contains a colon\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    # Convert to binary (1 for Psoriasis, 0 for PRP)\n",
    "    if \"psoriasis\" in value.lower():\n",
    "        return 1\n",
    "    elif \"pityriasis_rubra_pilaris\" in value.lower() or \"prp\" in value.lower():\n",
    "        return 0\n",
    "    return None\n",
    "\n",
    "def convert_age(value):\n",
    "    \"\"\"Convert age value to numeric format\"\"\"\n",
    "    # Not needed as age data is not available\n",
    "    return None\n",
    "\n",
    "def convert_gender(value):\n",
    "    \"\"\"Convert gender value to binary format (0 for female, 1 for male)\"\"\"\n",
    "    # Not needed as gender data is not available\n",
    "    return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "# Determine if trait data is available\n",
    "is_trait_available = trait_row is not None\n",
    "# Initial validation\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 data is available, extract clinical features\n",
    "if trait_row is not None:\n",
    "    # Assuming clinical_data is already defined from previous step\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",
    "    # Preview the dataframe\n",
    "    preview = preview_df(selected_clinical_df)\n",
    "    print(\"Preview of selected clinical features:\")\n",
    "    print(preview)\n",
    "    \n",
    "    # Save to CSV\n",
    "    selected_clinical_df.to_csv(out_clinical_data_file)\n",
    "    print(f\"Clinical data saved to {out_clinical_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "1a54da4e",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "ec02a445",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:13.037267Z",
     "iopub.status.busy": "2025-03-25T03:43:13.037125Z",
     "iopub.status.idle": "2025-03-25T03:43:13.169686Z",
     "shell.execute_reply": "2025-03-25T03:43:13.169350Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "First 20 gene/probe identifiers:\n",
      "Index(['1-Dec', '1-Sep', '10-Mar', '10-Sep', '11-Mar', '11-Sep', '12-Sep',\n",
      "       '14-Sep', '15-Sep', '2-Sep', '3-Mar', '3-Sep', '4-Mar', '4-Sep',\n",
      "       '5-Mar', '6-Mar', '6-Sep', '7-Mar', '7-Sep', '8-Mar'],\n",
      "      dtype='object', name='ID')\n",
      "\n",
      "Gene data dimensions: 29405 genes × 35 samples\n"
     ]
    }
   ],
   "source": [
    "# 1. Re-identify the SOFT and matrix files to ensure we have the correct paths\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. Extract the gene expression data from the matrix file\n",
    "gene_data = get_genetic_data(matrix_file)\n",
    "\n",
    "# 3. Print the first 20 row IDs (gene or probe identifiers)\n",
    "print(\"\\nFirst 20 gene/probe identifiers:\")\n",
    "print(gene_data.index[:20])\n",
    "\n",
    "# 4. Print the dimensions of the gene expression data\n",
    "print(f\"\\nGene data dimensions: {gene_data.shape[0]} genes × {gene_data.shape[1]} samples\")\n",
    "\n",
    "# Note: we keep is_gene_available as True since we successfully extracted gene expression data\n",
    "is_gene_available = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "0bdb63da",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "24473946",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:13.170896Z",
     "iopub.status.busy": "2025-03-25T03:43:13.170781Z",
     "iopub.status.idle": "2025-03-25T03:43:13.172692Z",
     "shell.execute_reply": "2025-03-25T03:43:13.172412Z"
    }
   },
   "outputs": [],
   "source": [
    "# Examine the gene identifiers in the dataset\n",
    "# The identifiers appear to be non-standard gene symbols (e.g., \"1-Dec\", \"1-Sep\", \"10-Mar\")\n",
    "# These are likely probe identifiers or some other format that requires mapping to standard gene symbols\n",
    "\n",
    "# Based on biomedical knowledge, standard human gene symbols would follow HGNC nomenclature\n",
    "# Examples of standard gene symbols: BRCA1, TP53, TNF, IL6, etc.\n",
    "# The identifiers seen here (like \"1-Dec\", \"3-Mar\") don't conform to standard gene symbol conventions\n",
    "\n",
    "# These identifiers need to be mapped to standard gene symbols for proper analysis\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "c775aeb6",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "8366578d",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:13.173764Z",
     "iopub.status.busy": "2025-03-25T03:43:13.173660Z",
     "iopub.status.idle": "2025-03-25T03:43:14.332202Z",
     "shell.execute_reply": "2025-03-25T03:43:14.331807Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Preview of SOFT file content:\n",
      "^DATABASE = GeoMiame\n",
      "!Database_name = Gene Expression Omnibus (GEO)\n",
      "!Database_institute = NCBI NLM NIH\n",
      "!Database_web_link = http://www.ncbi.nlm.nih.gov/geo\n",
      "!Database_email = [email protected]\n",
      "^SERIES = GSE183134\n",
      "!Series_title = Transcriptomic profiling of Pityriasis Rubra Pilaris (PRP) and Psoriasis\n",
      "!Series_geo_accession = GSE183134\n",
      "!Series_status = Public on Sep 30 2021\n",
      "!Series_submission_date = Aug 31 2021\n",
      "!Series_last_update_date = Jan 17 2022\n",
      "!Series_pubmed_id = 34491907\n",
      "!Series_summary = The microarray experiment was employed to evaluate the gene expressions in skin lesions of PRP and psoriasis.\n",
      "!Series_overall_design = To investigate the specific gene regulations, microarray profiling was performed on RNA extracted from paraffin embedded skin biopsy samples.\n",
      "!Series_type = Expression profiling by array\n",
      "!Series_contributor = Johann,E,Gudjonsson\n",
      "!Series_contributor = Lam,C,Tsoi\n",
      "!Series_sample_id = GSM5551681\n",
      "!Series_sample_id = GSM5551682\n",
      "!Series_sample_id = GSM5551683\n",
      "!Series_sample_id = GSM5551684\n",
      "...\n",
      "\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene annotation dataframe using default method:\n",
      "Shape: (1058615, 2)\n",
      "Columns: ['ID', 'SPOT_ID']\n",
      "          ID    SPOT_ID\n",
      "0    DDX11L1    DDX11L1\n",
      "1  MIR1302-2  MIR1302-2\n",
      "2      OR4F5      OR4F5\n",
      "\n",
      "Searching for platform annotation section in SOFT file...\n",
      "^PLATFORM = GPL30572\n",
      "!platform_table_begin\n",
      "ID\tSPOT_ID\n",
      "DDX11L1\tDDX11L1\n",
      "MIR1302-2\tMIR1302-2\n",
      "OR4F5\tOR4F5\n",
      "LOC100132287\tLOC100132287\n",
      "LOC105379690\tLOC105379690\n",
      "OR4F29\tOR4F29\n",
      "LOC105378947\tLOC105378947\n",
      "LOC105378580\tLOC105378580\n",
      "LOC100287934\tLOC100287934\n"
     ]
    }
   ],
   "source": [
    "# 1. First get the file paths using geo_get_relevant_filepaths function\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. Inspect the SOFT file structure to understand the annotation format\n",
    "# Read the first few lines of the SOFT file to examine its structure\n",
    "import gzip\n",
    "print(\"Preview of SOFT file content:\")\n",
    "with gzip.open(soft_file, 'rt') as f:\n",
    "    for i, line in enumerate(f):\n",
    "        print(line.strip())\n",
    "        if i >= 20:  # Print first 20 lines to understand structure\n",
    "            break\n",
    "print(\"...\\n\")\n",
    "\n",
    "# 3. Try different approaches to extract gene annotation data\n",
    "# First, let's try the default method to see what's actually in the file\n",
    "gene_annotation = get_gene_annotation(soft_file)\n",
    "print(\"Gene annotation dataframe using default method:\")\n",
    "print(f\"Shape: {gene_annotation.shape}\")\n",
    "print(f\"Columns: {gene_annotation.columns.tolist()}\")\n",
    "print(gene_annotation.head(3))\n",
    "\n",
    "# 4. Check if there's another section in the file that might contain the mapping\n",
    "# Look for platform annotation information in the SOFT file\n",
    "print(\"\\nSearching for platform annotation section in SOFT file...\")\n",
    "with gzip.open(soft_file, 'rt') as f:\n",
    "    platform_lines = []\n",
    "    capture = False\n",
    "    for i, line in enumerate(f):\n",
    "        if \"^PLATFORM\" in line:\n",
    "            capture = True\n",
    "            platform_lines.append(line.strip())\n",
    "        elif capture and line.startswith(\"!platform_table_begin\"):\n",
    "            platform_lines.append(line.strip())\n",
    "            for j in range(10):  # Capture the next 10 lines to understand the table structure\n",
    "                try:\n",
    "                    platform_line = next(f).strip()\n",
    "                    platform_lines.append(platform_line)\n",
    "                except StopIteration:\n",
    "                    break\n",
    "            break\n",
    "    \n",
    "    print(\"\\n\".join(platform_lines))\n",
    "\n",
    "# Maintain gene availability status as True based on previous steps\n",
    "is_gene_available = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "4513f69c",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "b726b7ef",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:14.333515Z",
     "iopub.status.busy": "2025-03-25T03:43:14.333386Z",
     "iopub.status.idle": "2025-03-25T03:43:16.373895Z",
     "shell.execute_reply": "2025-03-25T03:43:16.373428Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Platform annotation columns: ['ID', 'SPOT_ID']\n",
      "First few rows of platform annotation:\n",
      "             ID       SPOT_ID\n",
      "0       DDX11L1       DDX11L1\n",
      "1     MIR1302-2     MIR1302-2\n",
      "2         OR4F5         OR4F5\n",
      "3  LOC100132287  LOC100132287\n",
      "4  LOC105379690  LOC105379690\n",
      "Number of matching IDs between expression data and gene_annotation['ID']: 29405\n",
      "Mapping dataframe shape: (1058580, 2)\n",
      "             ID          Gene\n",
      "0       DDX11L1       DDX11L1\n",
      "1     MIR1302-2     MIR1302-2\n",
      "2         OR4F5         OR4F5\n",
      "3  LOC100132287  LOC100132287\n",
      "4  LOC105379690  LOC105379690\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Mapped gene expression data shape: (22785, 35)\n",
      "First few gene symbols: ['A1BG', 'A1BG-AS1', 'A1CF', 'A2M', 'A2M-AS1']\n"
     ]
    }
   ],
   "source": [
    "# 1. Examine both gene identifiers and annotation to determine mapping columns\n",
    "# From previous steps, we can see:\n",
    "# - The gene expression data has identifiers like \"1-Dec\", \"1-Sep\", \"10-Mar\" as index\n",
    "# - The gene annotation data shows columns \"ID\" and \"SPOT_ID\"\n",
    "\n",
    "# Since the gene annotation DataFrame doesn't seem to contain our probe identifiers directly,\n",
    "# we need to extract more detailed annotation from the SOFT file\n",
    "\n",
    "# Let's specifically look for the platform annotation that contains our probe IDs\n",
    "with gzip.open(soft_file, 'rt') as f:\n",
    "    platform_lines = []\n",
    "    capture = False\n",
    "    for line in f:\n",
    "        if \"!platform_table_begin\" in line:\n",
    "            capture = True\n",
    "            continue\n",
    "        elif \"!platform_table_end\" in line:\n",
    "            capture = False\n",
    "            break\n",
    "        elif capture:\n",
    "            platform_lines.append(line.strip())\n",
    "\n",
    "# Create a DataFrame from the platform lines if we found data\n",
    "if platform_lines:\n",
    "    import io\n",
    "    platform_df = pd.read_csv(io.StringIO('\\n'.join(platform_lines)), sep='\\t')\n",
    "    print(f\"Platform annotation columns: {platform_df.columns.tolist()}\")\n",
    "    print(f\"First few rows of platform annotation:\")\n",
    "    print(platform_df.head())\n",
    "else:\n",
    "    # If we couldn't find proper annotation, create a mapping from the gene expression data\n",
    "    # and annotation we already have\n",
    "    print(\"Could not find detailed probe-to-gene mapping in platform annotation.\")\n",
    "    # We'll proceed with the gene annotation we already extracted\n",
    "\n",
    "# 2. Get mapping between gene identifiers and gene symbols\n",
    "# Based on the output from previous steps, both ID and SPOT_ID columns in gene_annotation\n",
    "# appear to contain gene symbols. Let's check if either matches our expression data index\n",
    "\n",
    "# First, check if any IDs in gene_annotation match the expression data index\n",
    "matching_ids = len(set(gene_data.index) & set(gene_annotation['ID']))\n",
    "print(f\"Number of matching IDs between expression data and gene_annotation['ID']: {matching_ids}\")\n",
    "\n",
    "# If we didn't find matches, the gene identifiers might be in a different format\n",
    "# Let's try to extract mapping from additional annotation or metadata\n",
    "if matching_ids == 0:\n",
    "    print(\"No direct matches found. Creating alternative mapping...\")\n",
    "    \n",
    "    # For this dataset, it appears that the gene identifiers are non-standard, \n",
    "    # but the annotation provides standard gene symbols\n",
    "    # We'll create a simple 1:1 mapping using the annotation we have\n",
    "    \n",
    "    # Create a mapping dataframe where both probe ID and gene symbol are the same\n",
    "    # Since our gene identifiers don't seem to map directly to standard annotations,\n",
    "    # we'll use them as-is and treat them as approximations of gene symbols\n",
    "    mapping_df = pd.DataFrame({\n",
    "        'ID': gene_data.index,\n",
    "        'Gene': gene_data.index\n",
    "    })\n",
    "    \n",
    "    print(\"Created mapping with gene identifiers as gene symbols.\")\n",
    "    print(f\"Mapping dataframe shape: {mapping_df.shape}\")\n",
    "    print(mapping_df.head())\n",
    "else:\n",
    "    # If we found matching IDs, use them for mapping\n",
    "    mapping_df = gene_annotation[['ID', 'SPOT_ID']].rename(columns={'SPOT_ID': 'Gene'})\n",
    "    mapping_df = mapping_df[mapping_df['ID'].isin(gene_data.index)]\n",
    "    print(f\"Mapping dataframe shape: {mapping_df.shape}\")\n",
    "    print(mapping_df.head())\n",
    "\n",
    "# 3. Apply the gene mapping to convert probe-level measurements to gene-level expression\n",
    "gene_data_mapped = apply_gene_mapping(gene_data, mapping_df)\n",
    "print(f\"Mapped gene expression data shape: {gene_data_mapped.shape}\")\n",
    "print(f\"First few gene symbols: {list(gene_data_mapped.index[:5])}\")\n",
    "\n",
    "# Update gene_data to use the mapped values\n",
    "gene_data = gene_data_mapped\n",
    "\n",
    "# Maintain gene availability status\n",
    "is_gene_available = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "eeafc1a6",
   "metadata": {},
   "source": [
    "### Step 7: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "99be8255",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:43:16.375375Z",
     "iopub.status.busy": "2025-03-25T03:43:16.375261Z",
     "iopub.status.idle": "2025-03-25T03:43:27.729245Z",
     "shell.execute_reply": "2025-03-25T03:43:27.728882Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalizing gene symbols...\n",
      "Gene data shape after normalization: 22464 genes × 35 samples\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalized gene expression data saved to ../../output/preprocess/Psoriasis/gene_data/GSE183134.csv\n",
      "Extracting clinical features from the original source...\n",
      "Extracted clinical features preview:\n",
      "{'GSM5551681': [0.0], 'GSM5551682': [0.0], 'GSM5551683': [0.0], 'GSM5551684': [0.0], 'GSM5551685': [0.0], 'GSM5551686': [0.0], 'GSM5551687': [0.0], 'GSM5551688': [0.0], 'GSM5551689': [0.0], 'GSM5551690': [0.0], 'GSM5551691': [0.0], 'GSM5551692': [0.0], 'GSM5551693': [0.0], 'GSM5551694': [1.0], 'GSM5551695': [1.0], 'GSM5551696': [1.0], 'GSM5551697': [1.0], 'GSM5551698': [1.0], 'GSM5551699': [1.0], 'GSM5551700': [1.0], 'GSM5551701': [1.0], 'GSM5551702': [1.0], 'GSM5551703': [1.0], 'GSM5551704': [1.0], 'GSM5551705': [1.0], 'GSM5551706': [1.0], 'GSM5551707': [1.0], 'GSM5551708': [1.0], 'GSM5551709': [1.0], 'GSM5551710': [1.0], 'GSM5551711': [1.0], 'GSM5551712': [1.0], 'GSM5551713': [1.0], 'GSM5551714': [1.0], 'GSM5551715': [1.0]}\n",
      "Clinical data shape: (1, 35)\n",
      "Clinical features saved to ../../output/preprocess/Psoriasis/clinical_data/GSE183134.csv\n",
      "Linking clinical and genetic data...\n",
      "Linked data shape: (35, 22465)\n",
      "Handling missing values...\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Data shape after handling missing values: (35, 22465)\n",
      "\n",
      "Checking for bias in feature variables:\n",
      "For the feature 'Psoriasis', the least common label is '0.0' with 13 occurrences. This represents 37.14% of the dataset.\n",
      "The distribution of the feature 'Psoriasis' in this dataset is fine.\n",
      "\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Linked data saved to ../../output/preprocess/Psoriasis/GSE183134.csv\n",
      "Final dataset shape: (35, 22465)\n"
     ]
    }
   ],
   "source": [
    "# 1. Check if gene data is available after mapping\n",
    "if gene_data.shape[0] == 0:\n",
    "    print(\"Error: Gene expression matrix is empty after mapping.\")\n",
    "    # Mark the dataset as not usable due to lack of gene expression data\n",
    "    is_usable = validate_and_save_cohort_info(\n",
    "        is_final=True,\n",
    "        cohort=cohort,\n",
    "        info_path=json_path,\n",
    "        is_gene_available=False,  # No usable gene data\n",
    "        is_trait_available=True,\n",
    "        is_biased=True,\n",
    "        df=pd.DataFrame(),\n",
    "        note=\"Failed to map probe IDs to gene symbols. The annotation format may not be compatible with the extraction methods.\"\n",
    "    )\n",
    "    print(\"Dataset deemed not usable due to lack of gene expression data.\")\n",
    "else:\n",
    "    # Only proceed with normalization if we have gene data\n",
    "    print(\"Normalizing gene symbols...\")\n",
    "    gene_data_normalized = normalize_gene_symbols_in_index(gene_data)\n",
    "    print(f\"Gene data shape after normalization: {gene_data_normalized.shape[0]} genes × {gene_data_normalized.shape[1]} samples\")\n",
    "\n",
    "    # Save the normalized gene data\n",
    "    os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "    gene_data_normalized.to_csv(out_gene_data_file)\n",
    "    print(f\"Normalized gene expression data saved to {out_gene_data_file}\")\n",
    "    \n",
    "    # Extract clinical features from the original data source\n",
    "    print(\"Extracting clinical features from the original source...\")\n",
    "    # Get background information and clinical data again\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",
    "    # Extract 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=convert_gender\n",
    "    )\n",
    "    \n",
    "    print(\"Extracted clinical features preview:\")\n",
    "    print(preview_df(selected_clinical_df))\n",
    "    print(f\"Clinical data shape: {selected_clinical_df.shape}\")\n",
    "    \n",
    "    # Save the extracted clinical features\n",
    "    os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)\n",
    "    selected_clinical_df.to_csv(out_clinical_data_file)\n",
    "    print(f\"Clinical features saved to {out_clinical_data_file}\")\n",
    "    \n",
    "    # Link clinical and genetic data\n",
    "    print(\"Linking clinical and genetic data...\")\n",
    "    linked_data = geo_link_clinical_genetic_data(selected_clinical_df, gene_data_normalized)\n",
    "    print(f\"Linked data shape: {linked_data.shape}\")\n",
    "    \n",
    "    # Check if the linked data has adequate data\n",
    "    if linked_data.shape[0] == 0 or linked_data.shape[1] <= 4:  # 4 is an arbitrary small number\n",
    "        print(\"Error: Linked data has insufficient samples or features.\")\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=True,\n",
    "            df=linked_data,\n",
    "            note=\"Failed to properly link gene expression data with clinical features.\"\n",
    "        )\n",
    "        print(\"Dataset deemed not usable due to linking failure.\")\n",
    "    else:\n",
    "        # Handle missing values systematically\n",
    "        print(\"Handling missing values...\")\n",
    "        linked_data_clean = handle_missing_values(linked_data, trait_col=trait)\n",
    "        print(f\"Data shape after handling missing values: {linked_data_clean.shape}\")\n",
    "        \n",
    "        # Check if there are still samples after missing value handling\n",
    "        if linked_data_clean.shape[0] == 0:\n",
    "            print(\"Error: No samples remain after handling missing values.\")\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=True,\n",
    "                df=pd.DataFrame(),\n",
    "                note=\"All samples were removed during missing value handling.\"\n",
    "            )\n",
    "            print(\"Dataset deemed not usable as all samples were filtered out.\")\n",
    "        else:\n",
    "            # Check if the dataset is biased\n",
    "            print(\"\\nChecking for bias in feature variables:\")\n",
    "            is_biased, linked_data_final = judge_and_remove_biased_features(linked_data_clean, trait)\n",
    "            \n",
    "            # Conduct final quality validation\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_final,\n",
    "                note=\"Dataset contains gene expression data for Crohn's Disease patients, examining response to Infliximab treatment.\"\n",
    "            )\n",
    "            \n",
    "            # Save linked data if usable\n",
    "            if is_usable:\n",
    "                os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n",
    "                linked_data_final.to_csv(out_data_file)\n",
    "                print(f\"Linked data saved to {out_data_file}\")\n",
    "                print(f\"Final dataset shape: {linked_data_final.shape}\")\n",
    "            else:\n",
    "                print(\"Dataset deemed not usable for trait association studies, linked data not saved.\")"
   ]
  }
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