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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Adrenocortical_Cancer"
cohort = "GSE68606"

# Input paths
in_trait_dir = "../DATA/GEO/Adrenocortical_Cancer"
in_cohort_dir = "../DATA/GEO/Adrenocortical_Cancer/GSE68606"

# Output paths
out_data_file = "./output/preprocess/3/Adrenocortical_Cancer/GSE68606.csv"
out_gene_data_file = "./output/preprocess/3/Adrenocortical_Cancer/gene_data/GSE68606.csv"
out_clinical_data_file = "./output/preprocess/3/Adrenocortical_Cancer/clinical_data/GSE68606.csv"
json_path = "./output/preprocess/3/Adrenocortical_Cancer/cohort_info.json"

# Get file paths
soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)

# Extract background info and clinical data 
background_info, clinical_data = get_background_and_clinical_data(matrix_file)

# Get unique values per clinical feature
sample_characteristics = get_unique_values_by_row(clinical_data)

# Print background info
print("Dataset Background Information:")
print(f"{background_info}\n")

# Print sample characteristics
print("Sample Characteristics:")
for feature, values in sample_characteristics.items():
    print(f"Feature: {feature}")
    print(f"Values: {values}\n")
# 1. Gene Expression Data Availability
# Based on background info mentioning "gene expression analysis" and "Affymetrix Human Genome U133A arrays"
is_gene_available = True

# 2. Variable Availability and Data Type Conversion
# 2.1 Data Availability
# Trait (Adrenal Cortical Adenoma) in both disease state (1) and histology (7) 
trait_row = 1
# Age available in row 6
age_row = 6  
# Gender/Sex available in row 5
gender_row = 5

# 2.2 Data Type Conversion Functions
def convert_trait(x):
    # Extract value after colon and strip whitespace
    if ':' in str(x):
        value = str(x).split(':')[1].strip()
        # Binary: 1 if Adrenal Cortical Adenoma, 0 for others
        return 1 if 'Adrenal Cortical Adenoma' in value else 0
    return None

def convert_age(x):
    # Extract value after colon and strip whitespace
    if ':' in str(x):
        value = str(x).split(':')[1].strip()
        # Convert to float if numeric, otherwise None
        try:
            if value != '--':
                return float(value)
        except:
            pass
    return None

def convert_gender(x):
    # Extract value after colon and strip whitespace
    if ':' in str(x):
        value = str(x).split(':')[1].strip()
        # Convert to binary: 0 for female, 1 for male
        if value.lower() == 'female':
            return 0
        elif value.lower() == 'male':
            return 1
    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:
    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 = preview_df(clinical_features)
    print("Preview of clinical features:", preview)
    
    # Save to CSV
    os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)
    clinical_features.to_csv(out_clinical_data_file)
# Extract gene expression data from matrix file
gene_data = get_genetic_data(matrix_file)

# Print first 20 row IDs and shape of data to help debug
print("Shape of gene expression data:", gene_data.shape)
print("\nFirst few rows of data:")
print(gene_data.head())
print("\nFirst 20 gene/probe identifiers:")
print(gene_data.index[:20])

# Inspect a snippet of raw file to verify identifier format
import gzip
with gzip.open(matrix_file, 'rt', encoding='utf-8') as f:
    lines = []
    for i, line in enumerate(f):
        if "!series_matrix_table_begin" in line:
            # Get the next 5 lines after the marker
            for _ in range(5):
                lines.append(next(f).strip())
            break
print("\nFirst few lines after matrix marker in raw file:")
for line in lines:
    print(line)
# Observe IDs like '1007_s_at' which are Affymetrix probe IDs, not human gene symbols
# These need to be mapped to official gene symbols
requires_gene_mapping = True
# Get file paths using library function
soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)

# Extract gene annotation from SOFT file and get meaningful data 
gene_annotation = get_gene_annotation(soft_file)

# Preview gene annotation data
print("Gene annotation shape:", gene_annotation.shape)
print("\nGene annotation preview:")
print(preview_df(gene_annotation))

print("\nNumber of non-null values in each column:")
print(gene_annotation.count())

# Print example rows showing the mapping information columns
print("\nSample mapping columns ('ID' and 'Gene Symbol'):")
print("\nFirst 5 rows:")
print(gene_annotation[['ID', 'Gene Symbol']].head().to_string())

print("\nNote: Gene mapping will use:")
print("'ID' column: Probe identifiers") 
print("'Gene Symbol' column: Contains gene symbol information")
# Extract probe ID and gene symbol mapping
mapping_data = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='Gene Symbol')

# Convert probe data to gene expression by applying mapping
gene_data = apply_gene_mapping(gene_data, mapping_data)

# Save the gene expression data
os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)
gene_data.to_csv(out_gene_data_file)

# Print preview of mapped gene data
print("Gene expression data shape after mapping:", gene_data.shape)
print("\nPreview of gene expression data:")
print(preview_df(gene_data))
# 1. Load clinical data and save normalized gene data
selected_clinical = pd.read_csv(out_clinical_data_file, index_col=0)
gene_data.index = gene_data.index.str.replace('-mRNA', '')
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)

# 2. Link clinical and genetic data
linked_data = geo_link_clinical_genetic_data(selected_clinical, gene_data)

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

# 4. Check for biased features and remove them if needed 
is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)

# 5. Validate and save cohort info
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="Study examining gene expression changes in adipose tissue under different protein diets during energy restriction"
)

# 6. 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)