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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Hypothyroidism"
cohort = "GSE224330"

# Input paths
in_trait_dir = "../DATA/GEO/Hypothyroidism"
in_cohort_dir = "../DATA/GEO/Hypothyroidism/GSE224330"

# Output paths
out_data_file = "./output/preprocess/3/Hypothyroidism/GSE224330.csv"
out_gene_data_file = "./output/preprocess/3/Hypothyroidism/gene_data/GSE224330.csv"
out_clinical_data_file = "./output/preprocess/3/Hypothyroidism/clinical_data/GSE224330.csv"
json_path = "./output/preprocess/3/Hypothyroidism/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)

# Get unique values for each clinical feature 
unique_values_dict = get_unique_values_by_row(clinical_data)

# Print background information
print("Background Information:")
print(background_info)
print("\nSample Characteristics:")
print(json.dumps(unique_values_dict, indent=2))
# Gene expression data availability
# Yes, this dataset contains gene expression data as indicated by series title and summary
is_gene_available = True

# Data availability and type conversion
# Trait data (Hypothyroidism) can be extracted from comorbidity field
trait_row = 3
def convert_trait(value):
    if pd.isna(value):
        return None
    value = value.split(': ')[1].lower()
    if 'hypothyroidism' in value:
        return 1
    elif 'none' in value:
        return 0
    return None

# Age data is in row 1
age_row = 1
def convert_age(value):
    if pd.isna(value):
        return None
    try:
        return int(value.split(': ')[1].rstrip('y'))
    except:
        return None

# Gender data is in row 2  
gender_row = 2
def convert_gender(value):
    if pd.isna(value):
        return None
    value = value.split(': ')[1].lower()
    if 'female' in value:
        return 0
    elif 'male' in value:
        return 1
    return None

# Save initial filtering results
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
)

# Extract clinical features since trait_row is available
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
preview_df(clinical_features)

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

# Print first 20 row IDs
print("First 20 row IDs:")
print(genetic_data.index[:20].tolist())
# These identifiers appear to be Agilent probe IDs, not human gene symbols
# The format A_19_P00xxxxxx is characteristic of Agilent microarray probes
# We will need to map these to proper gene symbols
requires_gene_mapping = True
# Extract gene annotation data from SOFT file
gene_metadata = get_gene_annotation(soft_file_path)

# Display information about the annotation data
print("Column names:")
print(gene_metadata.columns.tolist())

# Look at general data statistics
print("\nData shape:", gene_metadata.shape)

# Display non-NaN value counts for key gene identifier columns
print("\nNumber of non-NaN values in key columns:")
for col in ['GENE_SYMBOL', 'GENE_NAME']:
    print(f"{col}: {gene_metadata[col].notna().sum()}")

# Preview rows with actual gene information
print("\nPreview of rows with gene information:")
gene_rows = gene_metadata[gene_metadata['GENE_SYMBOL'].notna()].head()
print(json.dumps(preview_df(gene_rows), indent=2))
# Get mapping between probes and gene symbols
mapping_data = get_gene_mapping(gene_metadata, prob_col='ID', gene_col='GENE_SYMBOL')

# Convert probe-level data to gene-level data using the mapping
gene_data = apply_gene_mapping(genetic_data, mapping_data)

# Save gene expression data
gene_data.to_csv(out_gene_data_file)

# Print statistics about the mapping
print(f"Original probe number: {len(genetic_data)}")
print(f"Number of probes with gene mapping: {len(mapping_data)}")
print(f"Final number of genes: {len(gene_data)}")
# 1. Normalize gene symbols
genetic_data = normalize_gene_symbols_in_index(gene_data)
genetic_data.to_csv(out_gene_data_file)

# Get clinical features
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
)

# 2. Link clinical and genetic data
linked_data = geo_link_clinical_genetic_data(clinical_features, genetic_data)

# 3. Handle missing values
linked_data = handle_missing_values(linked_data, trait)

# 4. Judge whether features are biased and remove biased demographic features
is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)

# 5. Final validation and save metadata
note = "Dataset contains gene expression data from breast cancer patients, with clinical annotations including hypothyroidism status."
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
)

# 6. Save the linked data only if it's usable
if is_usable:
    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
    linked_data.to_csv(out_data_file)