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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Substance_Use_Disorder"
cohort = "GSE161999"

# Input paths
in_trait_dir = "../DATA/GEO/Substance_Use_Disorder"
in_cohort_dir = "../DATA/GEO/Substance_Use_Disorder/GSE161999"

# Output paths
out_data_file = "./output/preprocess/3/Substance_Use_Disorder/GSE161999.csv"
out_gene_data_file = "./output/preprocess/3/Substance_Use_Disorder/gene_data/GSE161999.csv"
out_clinical_data_file = "./output/preprocess/3/Substance_Use_Disorder/clinical_data/GSE161999.csv"
json_path = "./output/preprocess/3/Substance_Use_Disorder/cohort_info.json"

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

# Get background info and clinical data
background_info, clinical_data = get_background_and_clinical_data(matrix_file_path)
print("Background Information:")
print(background_info)
print("\nSample Characteristics:")

# Get dictionary of unique values per row 
unique_values_dict = get_unique_values_by_row(clinical_data)
for row, values in unique_values_dict.items():
    print(f"\n{row}:")
    print(values)
# Gene expression data is available
is_gene_available = True  

# Key identification from sample characteristics
trait_row = 1  # 'diagnosis' field
age_row = 2    # 'age' field
gender_row = 3 # 'Sex' field

def convert_trait(value: str) -> int:
    """Convert diagnosis to binary: Control=0, Alcohol=1"""
    if not value or ':' not in value:
        return None
    val = value.split(':')[1].strip().lower()
    if val == 'control':
        return 0
    elif val == 'alcohol':
        return 1
    return None

def convert_age(value: str) -> float:
    """Convert age to continuous value"""
    if not value or ':' not in value:
        return None
    try:
        return float(value.split(':')[1].strip())
    except:
        return None

def convert_gender(value: str) -> int:
    """Convert gender to binary: Female=0, Male=1"""
    if not value or ':' not in value:
        return None
    val = value.split(':')[1].strip().lower()
    if val == 'female':
        return 0
    elif val == 'male':
        return 1
    return None

# Initial validation and saving metadata
is_trait_available = trait_row is not None
validate_and_save_cohort_info(is_final=False, 
                            cohort=cohort,
                            info_path=json_path,
                            is_gene_available=is_gene_available,
                            is_trait_available=is_trait_available)

# Extract clinical features since trait_row is not None
clinical_features = geo_select_clinical_features(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 clinical features
print("Preview of clinical features:")
print(preview_df(clinical_features))

# Save clinical features
clinical_features.to_csv(out_clinical_data_file)
# Get gene expression data from matrix file
genetic_data = get_genetic_data(matrix_file_path)

# Examine data structure
print("Data structure and head:")
print(genetic_data.head())

print("\nShape:", genetic_data.shape)

print("\nFirst 20 row IDs (gene/probe identifiers):")
print(list(genetic_data.index)[:20])

# Get a few column names to verify sample IDs
print("\nFirst 5 column names:")
print(list(genetic_data.columns)[:5])
# Looking at the identifiers like '1007_s_at', '1053_at', these are Affymetrix probe IDs,
# not standard human gene symbols. They need to be mapped to gene symbols.

requires_gene_mapping = True
# Extract gene annotation data
gene_annotation = get_gene_annotation(soft_file_path)

# Preview column names and values from annotation dataframe
print("Gene annotation DataFrame preview:")
print(preview_df(gene_annotation))
# The 'ID' column in gene annotation contains probe IDs that match the indices in genetic_data
# The 'Gene Symbol' column contains the corresponding gene symbols
mapping_data = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='Gene Symbol')

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

# Preview the resulting gene expression data
print("\nPreview of mapped gene expression data:")
print(gene_data.head())
print("\nShape after mapping:", gene_data.shape)
# 1. Normalize gene symbols in gene expression data
gene_data = normalize_gene_symbols_in_index(gene_data)
os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)
gene_data.to_csv(out_gene_data_file)
print("\nGene data shape (normalized gene-level):", gene_data.shape) 

# Load clinical data previously processed
selected_clinical_df = pd.read_csv(out_clinical_data_file, index_col=0)
print("\nClinical data shape:", selected_clinical_df.shape)

# 2. Link clinical and genetic data using normalized gene-level data
linked_data = geo_link_clinical_genetic_data(selected_clinical_df, gene_data)
print("\nLinked data shape:", linked_data.shape)

# 3. Handle missing values systematically  
if trait in linked_data.columns:
    linked_data = handle_missing_values(linked_data, trait)

    # 4. Check for bias in trait and demographic features
    trait_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)

    # 5. Final validation and information saving
    note = "Data was successfully preprocessed from probe-level to gene-level expression using gene symbol normalization with NCBI Gene database."
    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=trait_biased,
        df=linked_data,
        note=note
    )

    # 6. Save linked data only if usable and not biased
    if is_usable and not trait_biased:
        os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
        linked_data.to_csv(out_data_file)