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{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "ea4e4b5e",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:44:24.643857Z",
     "iopub.status.busy": "2025-03-25T03:44:24.643618Z",
     "iopub.status.idle": "2025-03-25T03:44:24.813079Z",
     "shell.execute_reply": "2025-03-25T03:44:24.812738Z"
    }
   },
   "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",
    "\n",
    "# Input paths\n",
    "tcga_root_dir = \"../../input/TCGA\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Psoriasis/TCGA.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Psoriasis/gene_data/TCGA.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Psoriasis/clinical_data/TCGA.csv\"\n",
    "json_path = \"../../output/preprocess/Psoriasis/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "7da519b5",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "23eb0dfc",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:44:24.814516Z",
     "iopub.status.busy": "2025-03-25T03:44:24.814375Z",
     "iopub.status.idle": "2025-03-25T03:44:25.945837Z",
     "shell.execute_reply": "2025-03-25T03:44:25.945470Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Looking for a relevant directory for Psoriasis among 38 TCGA directories\n",
      "Selected TCGA_Melanoma_(SKCM) as the most relevant directory for Psoriasis\n",
      "Clinical data file: TCGA.SKCM.sampleMap_SKCM_clinicalMatrix\n",
      "Genetic data file: TCGA.SKCM.sampleMap_HiSeqV2_PANCAN.gz\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Clinical data shape: (481, 93)\n",
      "Genetic data shape: (20530, 474)\n",
      "\n",
      "Clinical data columns:\n",
      "['_INTEGRATION', '_PATIENT', '_cohort', '_primary_disease', '_primary_site', 'additional_pharmaceutical_therapy', 'additional_radiation_therapy', 'age_at_initial_pathologic_diagnosis', 'bcr_followup_barcode', 'bcr_patient_barcode', 'bcr_sample_barcode', 'breslow_depth_value', 'days_to_birth', 'days_to_collection', 'days_to_death', 'days_to_initial_pathologic_diagnosis', 'days_to_last_followup', 'days_to_new_tumor_event_additional_surgery_procedure', 'days_to_new_tumor_event_after_initial_treatment', 'days_to_submitted_specimen_dx', 'distant_metastasis_anatomic_site', 'followup_case_report_form_submission_reason', 'form_completion_date', 'gender', 'height', 'history_of_neoadjuvant_treatment', 'icd_10', 'icd_o_3_histology', 'icd_o_3_site', 'informed_consent_verified', 'initial_weight', 'interferon_90_day_prior_excision_admin_indicator', 'is_ffpe', 'lactate_dehydrogenase_result', 'lost_follow_up', 'malignant_neoplasm_mitotic_count_rate', 'melanoma_clark_level_value', 'melanoma_origin_skin_anatomic_site', 'melanoma_ulceration_indicator', 'new_neoplasm_event_occurrence_anatomic_site', 'new_neoplasm_event_type', 'new_non_melanoma_event_histologic_type_text', 'new_primary_melanoma_anatomic_site', 'new_tumor_dx_prior_submitted_specimen_dx', 'new_tumor_event_additional_surgery_procedure', 'new_tumor_event_after_initial_treatment', 'new_tumor_metastasis_anatomic_site', 'new_tumor_metastasis_anatomic_site_other_text', 'oct_embedded', 'other_dx', 'pathologic_M', 'pathologic_N', 'pathologic_T', 'pathologic_stage', 'pathology_report_file_name', 'patient_id', 'person_neoplasm_cancer_status', 'postoperative_rx_tx', 'primary_anatomic_site_count', 'primary_melanoma_at_diagnosis_count', 'primary_neoplasm_melanoma_dx', 'primary_tumor_multiple_present_ind', 'prior_systemic_therapy_type', 'radiation_therapy', 'sample_type', 'sample_type_id', 'subsequent_primary_melanoma_during_followup', 'system_version', 'tissue_prospective_collection_indicator', 'tissue_retrospective_collection_indicator', 'tissue_source_site', 'tissue_type', 'tumor_descriptor', 'tumor_tissue_site', 'vial_number', 'vital_status', 'weight', 'year_of_initial_pathologic_diagnosis', '_GENOMIC_ID_TCGA_SKCM_exp_HiSeqV2', '_GENOMIC_ID_TCGA_SKCM_hMethyl450', '_GENOMIC_ID_TCGA_SKCM_exp_HiSeqV2_PANCAN', '_GENOMIC_ID_TCGA_SKCM_miRNA_HiSeq', '_GENOMIC_ID_TCGA_SKCM_gistic2thd', '_GENOMIC_ID_data/public/TCGA/SKCM/miRNA_HiSeq_gene', '_GENOMIC_ID_TCGA_SKCM_RPPA', '_GENOMIC_ID_TCGA_SKCM_mutation_bcm_gene', '_GENOMIC_ID_TCGA_SKCM_mutation_broad_gene', '_GENOMIC_ID_TCGA_SKCM_gistic2', '_GENOMIC_ID_TCGA_SKCM_mutation', '_GENOMIC_ID_TCGA_SKCM_exp_HiSeqV2_exon', '_GENOMIC_ID_TCGA_SKCM_PDMRNAseqCNV', '_GENOMIC_ID_TCGA_SKCM_PDMRNAseq', '_GENOMIC_ID_TCGA_SKCM_exp_HiSeqV2_percentile']\n"
     ]
    }
   ],
   "source": [
    "import os\n",
    "import pandas as pd\n",
    "\n",
    "# Step 1: Review TCGA subdirectories to find the most relevant one for Psoriasis\n",
    "available_dirs = os.listdir(tcga_root_dir)\n",
    "print(f\"Looking for a relevant directory for {trait} among {len(available_dirs)} TCGA directories\")\n",
    "\n",
    "# Psoriasis is a skin condition. TCGA_Melanoma_(SKCM) is the closest match as it deals with skin cancer\n",
    "# While not the same disease, it's the closest skin-related dataset in TCGA\n",
    "relevant_dir = \"TCGA_Melanoma_(SKCM)\"\n",
    "\n",
    "# Check if our chosen directory exists\n",
    "if relevant_dir not in available_dirs:\n",
    "    print(f\"No suitable directory found for {trait}. The closest candidate would be {relevant_dir}.\")\n",
    "    # Record this information and exit\n",
    "    validate_and_save_cohort_info(is_final=False, cohort=\"TCGA\", info_path=json_path, \n",
    "                                 is_gene_available=False, is_trait_available=False)\n",
    "    exit()\n",
    "else:\n",
    "    print(f\"Selected {relevant_dir} as the most relevant directory for {trait}\")\n",
    "    \n",
    "    # Step 2: Identify paths to clinical and genetic data files\n",
    "    cohort_dir = os.path.join(tcga_root_dir, relevant_dir)\n",
    "    clinical_file_path, genetic_file_path = tcga_get_relevant_filepaths(cohort_dir)\n",
    "    \n",
    "    print(f\"Clinical data file: {os.path.basename(clinical_file_path)}\")\n",
    "    print(f\"Genetic data file: {os.path.basename(genetic_file_path)}\")\n",
    "    \n",
    "    # Step 3: Load the clinical and genetic data files\n",
    "    try:\n",
    "        clinical_df = pd.read_csv(clinical_file_path, index_col=0, sep='\\t')\n",
    "        genetic_df = pd.read_csv(genetic_file_path, index_col=0, sep='\\t')\n",
    "        \n",
    "        print(f\"Clinical data shape: {clinical_df.shape}\")\n",
    "        print(f\"Genetic data shape: {genetic_df.shape}\")\n",
    "        \n",
    "        # Step 4: Print the column names of the clinical data\n",
    "        print(\"\\nClinical data columns:\")\n",
    "        print(clinical_df.columns.tolist())\n",
    "        \n",
    "        # Check if both datasets have data\n",
    "        is_gene_available = genetic_df.shape[0] > 0 and genetic_df.shape[1] > 0\n",
    "        is_trait_available = clinical_df.shape[0] > 0 and clinical_df.shape[1] > 0\n",
    "        \n",
    "        # Record initial validation\n",
    "        validate_and_save_cohort_info(is_final=False, cohort=\"TCGA\", info_path=json_path, \n",
    "                                     is_gene_available=is_gene_available, is_trait_available=is_trait_available)\n",
    "        \n",
    "    except Exception as e:\n",
    "        print(f\"Error loading data: {e}\")\n",
    "        validate_and_save_cohort_info(is_final=False, cohort=\"TCGA\", info_path=json_path, \n",
    "                                     is_gene_available=False, is_trait_available=False)\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "61f40c3f",
   "metadata": {},
   "source": [
    "### Step 2: Find Candidate Demographic Features"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "c133dc38",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:44:25.947053Z",
     "iopub.status.busy": "2025-03-25T03:44:25.946942Z",
     "iopub.status.idle": "2025-03-25T03:44:25.956011Z",
     "shell.execute_reply": "2025-03-25T03:44:25.955719Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Age columns preview:\n",
      "{'age_at_initial_pathologic_diagnosis': [71.0, 82.0, 82.0, 46.0, 74.0], 'days_to_birth': [-26176.0, -30286.0, -30163.0, -17025.0, -27124.0]}\n",
      "Gender columns preview:\n",
      "{'gender': ['MALE', 'MALE', 'MALE', 'FEMALE', 'FEMALE']}\n"
     ]
    }
   ],
   "source": [
    "# Identify candidate columns for age and gender\n",
    "candidate_age_cols = ['age_at_initial_pathologic_diagnosis', 'days_to_birth']\n",
    "candidate_gender_cols = ['gender']\n",
    "\n",
    "# Get clinical data file path\n",
    "clinical_file_path, genetic_file_path = tcga_get_relevant_filepaths(f\"{tcga_root_dir}/TCGA_Melanoma_(SKCM)\")\n",
    "\n",
    "# Load clinical data\n",
    "clinical_df = pd.read_csv(clinical_file_path, sep='\\t', index_col=0)\n",
    "\n",
    "# Extract and preview candidate age columns\n",
    "if candidate_age_cols:\n",
    "    age_preview = {col: clinical_df[col].head(5).tolist() for col in candidate_age_cols}\n",
    "    print(\"Age columns preview:\")\n",
    "    print(age_preview)\n",
    "\n",
    "# Extract and preview candidate gender columns\n",
    "if candidate_gender_cols:\n",
    "    gender_preview = {col: clinical_df[col].head(5).tolist() for col in candidate_gender_cols}\n",
    "    print(\"Gender columns preview:\")\n",
    "    print(gender_preview)\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "332e1189",
   "metadata": {},
   "source": [
    "### Step 3: Select Demographic Features"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "92a2ab8b",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:44:25.957042Z",
     "iopub.status.busy": "2025-03-25T03:44:25.956922Z",
     "iopub.status.idle": "2025-03-25T03:44:25.959085Z",
     "shell.execute_reply": "2025-03-25T03:44:25.958806Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Selected age column: age_at_initial_pathologic_diagnosis\n",
      "Selected gender column: gender\n"
     ]
    }
   ],
   "source": [
    "# 1. Select appropriate columns for age and gender\n",
    "\n",
    "# Age column selection\n",
    "# Both columns seem to contain valid age information\n",
    "# 'age_at_initial_pathologic_diagnosis' is more directly usable as it's already in years\n",
    "# 'days_to_birth' would need conversion (it's negative days from birth to diagnosis)\n",
    "age_col = 'age_at_initial_pathologic_diagnosis'\n",
    "\n",
    "# Gender column selection\n",
    "# The 'gender' column looks appropriate with valid values ('MALE', 'FEMALE')\n",
    "gender_col = 'gender'\n",
    "\n",
    "# 2. Print the chosen columns\n",
    "print(f\"Selected age column: {age_col}\")\n",
    "print(f\"Selected gender column: {gender_col}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "78c3b4e5",
   "metadata": {},
   "source": [
    "### Step 4: Feature Engineering and Validation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "b1e4b40b",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T03:44:25.960017Z",
     "iopub.status.busy": "2025-03-25T03:44:25.959908Z",
     "iopub.status.idle": "2025-03-25T03:44:39.169541Z",
     "shell.execute_reply": "2025-03-25T03:44:39.168991Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Processed clinical data (shape: (481, 3)) saved to ../../output/preprocess/Psoriasis/clinical_data/TCGA.csv\n",
      "Clinical data preview:\n",
      "                 Psoriasis   Age  Gender\n",
      "sampleID                                \n",
      "TCGA-3N-A9WB-06          1  71.0     1.0\n",
      "TCGA-3N-A9WC-06          1  82.0     1.0\n",
      "TCGA-3N-A9WD-06          1  82.0     1.0\n",
      "TCGA-BF-A1PU-01          1  46.0     0.0\n",
      "TCGA-BF-A1PV-01          1  74.0     0.0\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Original genetic data shape: (20530, 474)\n",
      "Normalized genetic data shape: (19848, 474)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Processed gene data saved to ../../output/preprocess/Psoriasis/gene_data/TCGA.csv\n",
      "Number of common samples between clinical and genetic data: 474\n",
      "Linked data shape: (474, 19851)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Data shape after handling missing values: (474, 19851)\n",
      "For the feature 'Psoriasis', the least common label is '0' with 1 occurrences. This represents 0.21% of the dataset.\n",
      "The distribution of the feature 'Psoriasis' in this dataset is severely biased.\n",
      "\n",
      "Quartiles for 'Age':\n",
      "  25%: 48.0\n",
      "  50% (Median): 58.0\n",
      "  75%: 70.75\n",
      "Min: 15.0\n",
      "Max: 90.0\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 180 occurrences. This represents 37.97% of the dataset.\n",
      "The distribution of the feature 'Gender' in this dataset is fine.\n",
      "\n",
      "Is the trait distribution biased? True\n",
      "Data shape after removing biased features: (474, 19851)\n",
      "Data was deemed not usable for Psoriasis analysis - no final file saved.\n"
     ]
    }
   ],
   "source": [
    "# 1. Extract and standardize clinical features\n",
    "# Use tcga_select_clinical_features to extract trait (Psoriasis) and demographic info\n",
    "# For TCGA datasets, we use sample ID patterns to determine the trait (tumor vs normal)\n",
    "clinical_file_path, genetic_file_path = tcga_get_relevant_filepaths(f\"{tcga_root_dir}/TCGA_Melanoma_(SKCM)\")\n",
    "clinical_df = pd.read_csv(clinical_file_path, sep='\\t', index_col=0)\n",
    "selected_clinical_df = tcga_select_clinical_features(clinical_df, trait, age_col, gender_col)\n",
    "\n",
    "# Save the processed clinical data\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\"Processed clinical data (shape: {selected_clinical_df.shape}) saved to {out_clinical_data_file}\")\n",
    "print(f\"Clinical data preview:\")\n",
    "print(selected_clinical_df.head())\n",
    "\n",
    "# 2. Normalize gene symbols in the genetic data\n",
    "genetic_df = pd.read_csv(genetic_file_path, sep='\\t', index_col=0)\n",
    "print(f\"Original genetic data shape: {genetic_df.shape}\")\n",
    "\n",
    "# Apply normalization using the NCBI Gene database\n",
    "normalized_genetic_df = normalize_gene_symbols_in_index(genetic_df)\n",
    "print(f\"Normalized genetic data shape: {normalized_genetic_df.shape}\")\n",
    "\n",
    "# Save the normalized gene expression data\n",
    "os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "normalized_genetic_df.to_csv(out_gene_data_file)\n",
    "print(f\"Processed gene data saved to {out_gene_data_file}\")\n",
    "\n",
    "# 3. Link clinical and genetic data\n",
    "# In TCGA datasets, we need to ensure that indexes (sample IDs) match between datasets\n",
    "common_samples = set(selected_clinical_df.index).intersection(set(normalized_genetic_df.columns))\n",
    "print(f\"Number of common samples between clinical and genetic data: {len(common_samples)}\")\n",
    "\n",
    "# Filter both dataframes to include only common samples\n",
    "selected_clinical_df = selected_clinical_df.loc[selected_clinical_df.index.isin(common_samples)]\n",
    "normalized_genetic_df = normalized_genetic_df[list(common_samples)]\n",
    "\n",
    "# Combine clinical and genetic data\n",
    "linked_data = selected_clinical_df.join(normalized_genetic_df.T)\n",
    "print(f\"Linked data shape: {linked_data.shape}\")\n",
    "\n",
    "# 4. Handle missing values\n",
    "linked_data = handle_missing_values(linked_data, trait)\n",
    "print(f\"Data shape after handling missing values: {linked_data.shape}\")\n",
    "\n",
    "# 5. Determine if trait and demographic features are biased\n",
    "is_biased, cleaned_data = judge_and_remove_biased_features(linked_data, trait)\n",
    "print(f\"Is the trait distribution biased? {is_biased}\")\n",
    "print(f\"Data shape after removing biased features: {cleaned_data.shape}\")\n",
    "\n",
    "# 6. Validate the quality of the data and save metadata\n",
    "is_usable = validate_and_save_cohort_info(\n",
    "    is_final=True,\n",
    "    cohort=\"TCGA\",\n",
    "    info_path=json_path,\n",
    "    is_gene_available=True,\n",
    "    is_trait_available=True,\n",
    "    is_biased=is_biased,\n",
    "    df=cleaned_data,\n",
    "    note=f\"Data from TCGA Melanoma (SKCM) cohort was used as a proxy for {trait}.\"\n",
    ")\n",
    "\n",
    "# 7. Save the linked data if it's usable\n",
    "if is_usable:\n",
    "    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n",
    "    cleaned_data.to_csv(out_data_file)\n",
    "    print(f\"Final processed data saved to {out_data_file}\")\n",
    "else:\n",
    "    print(f\"Data was deemed not usable for {trait} analysis - no final file saved.\")"
   ]
  }
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