# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Pheochromocytoma_and_Paraganglioma"
cohort = "GSE19422"

# Input paths
in_trait_dir = "../DATA/GEO/Pheochromocytoma_and_Paraganglioma"
in_cohort_dir = "../DATA/GEO/Pheochromocytoma_and_Paraganglioma/GSE19422"

# Output paths
out_data_file = "./output/preprocess/3/Pheochromocytoma_and_Paraganglioma/GSE19422.csv"
out_gene_data_file = "./output/preprocess/3/Pheochromocytoma_and_Paraganglioma/gene_data/GSE19422.csv"
out_clinical_data_file = "./output/preprocess/3/Pheochromocytoma_and_Paraganglioma/clinical_data/GSE19422.csv"
json_path = "./output/preprocess/3/Pheochromocytoma_and_Paraganglioma/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 the background info mentioning "Gene expression profiling" and "cDNA microarray",
# this dataset contains gene expression data
is_gene_available = True 

# 2.1 Row identifiers for clinical features
# tissue type indicates tumor/normal status (trait)
trait_row = 0  

# Age and gender are not available in sample characteristics
age_row = None
gender_row = None

# 2.2 Data type conversion functions
def convert_trait(value):
    """Convert tissue type to binary: 1 for tumor (PCC/PGL), 0 for normal"""
    if not value or ':' not in value:
        return None
    value = value.split(':')[1].strip().lower()
    if 'normal' in value:
        return 0
    elif 'tumor' in value or 'pcc' in value or 'pgl' in value:
        return 1
    return None

convert_age = None
convert_gender = None

# 3. Save metadata about data availability
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 clinical features since trait data 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
print("Preview of clinical features:")
print(preview_df(clinical_features))

# Save clinical data
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])
# Based on the gene identifiers which start with "A_23_P", these are Agilent microarray probe IDs, not gene symbols
# They need to be mapped to human gene symbols for analysis
requires_gene_mapping = True
# Extract gene annotation data
gene_annotation = get_gene_annotation(soft_file_path)

# Display column names and preview data
print("Column names:")
print(gene_annotation.columns)

print("\nPreview of gene annotation data:")
print(preview_df(gene_annotation))
# Get gene mapping data
# 'ID' in gene annotation matches probe IDs in expression data
# 'GENE_SYMBOL' contains the target gene symbols
mapping_data = get_gene_mapping(gene_annotation, 'ID', 'GENE_SYMBOL')

# Convert probe measurements to gene expression data
gene_data = apply_gene_mapping(genetic_data, mapping_data)

# Preview results
print("Shape of original probe data:", genetic_data.shape)
print("Shape after mapping to genes:", gene_data.shape)
print("\nFirst few rows and columns of gene expression data:")
print(gene_data.head().iloc[:, :5])
# Reload clinical data that was processed earlier
selected_clinical_df = pd.read_csv(out_clinical_data_file, index_col=0)

# 1. Normalize gene symbols
genetic_data = normalize_gene_symbols_in_index(gene_data)
genetic_data.to_csv(out_gene_data_file)

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

# 3. Handle missing values systematically  
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 = "Dataset contains gene expression data from adrenal tissue samples, with cases identified by presence of pheochromocytoma"
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 
if is_usable:
    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
    linked_data.to_csv(out_data_file)