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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Glucocorticoid_Sensitivity"
cohort = "GSE33649"

# Input paths
in_trait_dir = "../DATA/GEO/Glucocorticoid_Sensitivity"
in_cohort_dir = "../DATA/GEO/Glucocorticoid_Sensitivity/GSE33649"

# Output paths
out_data_file = "./output/preprocess/3/Glucocorticoid_Sensitivity/GSE33649.csv"
out_gene_data_file = "./output/preprocess/3/Glucocorticoid_Sensitivity/gene_data/GSE33649.csv"
out_clinical_data_file = "./output/preprocess/3/Glucocorticoid_Sensitivity/clinical_data/GSE33649.csv"
json_path = "./output/preprocess/3/Glucocorticoid_Sensitivity/cohort_info.json"

# Get relevant file paths
soft_file_path, matrix_file_path = geo_get_relevant_filepaths(in_cohort_dir)

# Extract background info and clinical data from the matrix file
background_info, clinical_data = get_background_and_clinical_data(matrix_file_path)

# Get dictionary of unique values per row in clinical data
unique_values_dict = get_unique_values_by_row(clinical_data)

# Print background info
print("Background Information:")
print("-" * 50)
print(background_info)
print("\n")

# Print clinical data unique values
print("Sample Characteristics:")
print("-" * 50)
for row, values in unique_values_dict.items():
    print(f"{row}:")
    print(f"  {values}")
    print()
# 1. Gene Expression Data Availability
# Yes, this dataset contains gene expression data as it studies transcriptome-wide response
is_gene_available = True

# 2. Variable Availability and Data Type Conversion
# 2.1 Data Availability
trait_row = 3  # LGS is recorded in row 3
age_row = 6    # Age is recorded in row 6
gender_row = 5  # Gender is recorded in row 5

# 2.2 Data Type Conversion Functions
def convert_trait(x: str) -> Optional[float]:
    """Convert lymphocyte GC sensitivity values to float"""
    try:
        # Extract numeric value after the colon
        value = x.split(': ')[1]
        return float(value)
    except:
        return None

def convert_age(x: str) -> Optional[float]:
    """Convert age values to float"""
    try:
        # Extract numeric value after the colon
        value = x.split(': ')[1]
        return float(value)
    except:
        return None

def convert_gender(x: str) -> Optional[int]:
    """Convert gender to binary (0=female, 1=male)"""
    try:
        value = x.split(': ')[1].lower()
        if value == 'female':
            return 0
        elif value == 'male':
            return 1
        return None
    except:
        return None

# 3. Save Metadata 
validate_and_save_cohort_info(is_final=False, 
                            cohort=cohort,
                            info_path=json_path,
                            is_gene_available=is_gene_available,
                            is_trait_available=(trait_row is not None))

# 4. Clinical Feature Extraction
if trait_row is not None:
    # Extract features using the library function
    clinical_features = geo_select_clinical_features(
        clinical_df=clinical_data,
        trait=trait,
        trait_row=trait_row,
        convert_trait=convert_trait,
        age_row=age_row,
        convert_age=convert_age,
        gender_row=gender_row,
        convert_gender=convert_gender
    )
    
    # Preview the extracted features
    print("Preview of extracted clinical features:")
    print(preview_df(clinical_features))
    
    # Save to CSV
    clinical_features.to_csv(out_clinical_data_file)
# Extract gene expression data
genetic_data = get_genetic_data(matrix_file_path)

# Print first 20 probe IDs
print("First 20 probe IDs:")
print(genetic_data.index[:20])
# These identifiers are ILMN_ Illumina probe IDs, not gene symbols
# They need to be mapped to human gene symbols for biological interpretation
requires_gene_mapping = True
# Extract gene annotation from SOFT file
gene_annotation = get_gene_annotation(soft_file_path)

# Preview column names and first few values
preview_dict = preview_df(gene_annotation)
print("Column names and preview values:")
for col, values in preview_dict.items():
    print(f"\n{col}:")
    print(values)
# 1. The 'ID' column in annotation matches probe IDs in expression data
# The 'Symbol' column contains gene symbols
prob_col = 'ID'
gene_col = 'Symbol'

# 2. Get mapping between probe IDs and gene symbols 
mapping_data = get_gene_mapping(gene_annotation, prob_col, gene_col)

# 3. Apply mapping to convert probe-level data to gene expression data
gene_data = apply_gene_mapping(genetic_data, mapping_data)

# Print first few gene symbols to verify mapping
print("\nFirst 20 gene symbols after mapping:")
print(gene_data.index[:20])
# 1. Normalize gene symbols and save normalized gene data
normalized_gene_data = normalize_gene_symbols_in_index(gene_data)
os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)
normalized_gene_data.to_csv(out_gene_data_file)

# Read the processed clinical data file 
clinical_df = pd.read_csv(out_clinical_data_file, index_col=0)

# Link clinical and genetic data using the normalized gene data
linked_data = geo_link_clinical_genetic_data(clinical_df, normalized_gene_data)

# Handle missing values systematically
linked_data = handle_missing_values(linked_data, trait)

# Detect bias in trait and demographic features, remove biased demographic features
is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)

# Validate data quality and save cohort info
note = "Gene expression data from glucocorticoid sensitivity study."
is_usable = validate_and_save_cohort_info(
    is_final=True,
    cohort=cohort,
    info_path=json_path,
    is_gene_available=True,
    is_trait_available=True,
    is_biased=is_biased,
    df=linked_data,
    note=note
)

# Save linked data if usable
if is_usable:
    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
    linked_data.to_csv(out_data_file)
else:
    print(f"Dataset {cohort} did not pass quality validation and will not be saved.")