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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Substance_Use_Disorder"
cohort = "GSE138297"

# Input paths
in_trait_dir = "../DATA/GEO/Substance_Use_Disorder"
in_cohort_dir = "../DATA/GEO/Substance_Use_Disorder/GSE138297"

# Output paths
out_data_file = "./output/preprocess/3/Substance_Use_Disorder/GSE138297.csv"
out_gene_data_file = "./output/preprocess/3/Substance_Use_Disorder/gene_data/GSE138297.csv"
out_clinical_data_file = "./output/preprocess/3/Substance_Use_Disorder/clinical_data/GSE138297.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)
# 1. Gene Expression Data Availability
# Based on background info, this is a microarray study of gene expression in colon biopsies
is_gene_available = True 

# 2.1 Data Availability
# Key identification:
# Trait - experimental condition (row 6) can be used to define case/control
trait_row = 6
# Age - age in years available (row 3)
age_row = 3  
# Gender - sex data available (row 1) 
gender_row = 1

# 2.2 Data Type Conversion Functions
def convert_trait(value):
    if not value or ':' not in value:
        return None
    condition = value.split(': ')[1].strip()
    # Autologous FMT (self) as control (0), Allogenic FMT (from donor) as case (1)
    if 'Autologous' in condition:
        return 0
    elif 'Allogenic' in condition:
        return 1
    return None

def convert_age(value):
    if not value or ':' not in value:
        return None
    try:
        return float(value.split(': ')[1])
    except:
        return None

def convert_gender(value):
    if not value or ':' not in value:
        return None
    try:
        # Data already coded as female=1, male=0
        # Need to reverse to match our convention (female=0, male=1)
        gender_val = int(value.split(': ')[1])
        return 1 - gender_val  # Reverse the coding
    except:
        return None

# 3. Save initial 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. Extract and save clinical features
if trait_row is not None:
    selected_clinical = 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 = preview_df(selected_clinical)
    print("Preview of selected clinical features:", preview)
    
    # Save clinical data
    selected_clinical.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])
# The IDs in the data (e.g. 16650001, 16650003 etc.) appear to be probe/array IDs 
# and not standard human gene symbols like BRCA1, TP53 etc.
# This indicates we need to map these IDs to their corresponding gene symbols
requires_gene_mapping = True
# Extract gene annotation from SOFT file 
gene_annotation = get_gene_annotation(soft_file_path)

# Preview annotation structure
preview = preview_df(gene_annotation)
print("Gene annotation preview:")
print(preview)
# 1. Identify the probe ID column and gene symbol column
# From the preview, 'ID' matches the gene expression data identifiers
# The gene symbols are in 'gene_assignment' column 

# 2. Get gene mapping dataframe
mapping_data = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='gene_assignment')

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

# 4. Normalize gene symbols 
gene_data = normalize_gene_symbols_in_index(gene_data)

# Preview results
print("Shape after mapping:", gene_data.shape)
print("\nFirst few genes and samples:")
print(gene_data.iloc[:5, :5])
# 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)