# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Sickle_Cell_Anemia"
cohort = "GSE84634"

# Input paths
in_trait_dir = "../DATA/GEO/Sickle_Cell_Anemia"
in_cohort_dir = "../DATA/GEO/Sickle_Cell_Anemia/GSE84634"

# Output paths
out_data_file = "./output/preprocess/3/Sickle_Cell_Anemia/GSE84634.csv"
out_gene_data_file = "./output/preprocess/3/Sickle_Cell_Anemia/gene_data/GSE84634.csv"
out_clinical_data_file = "./output/preprocess/3/Sickle_Cell_Anemia/clinical_data/GSE84634.csv"
json_path = "./output/preprocess/3/Sickle_Cell_Anemia/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
# Dataset is about gene expression in PBMCs, so gene data should be available
is_gene_available = True

# 2. Variable Availability and Data Type Conversion
# 2.1 Data Availability
# trait_row = 2 since disease status is recorded in row 2
# age and gender not recorded in characteristics 
trait_row = 2
age_row = None  
gender_row = None

# 2.2 Data Type Conversion Functions
def convert_trait(x):
    # Binary conversion - SCD patients are cases (1), non-SCD would be controls (0)
    # But here all subjects are SCD patients based on background info
    if x and 'sickle cell disease' in x.lower():
        return 1
    return None

def convert_age(x):
    # Not available
    return None

def convert_gender(x):
    # Not available 
    return None

# 3. Save 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)

# 4. Clinical Feature Extraction
if trait_row is not None:
    clinical_df = 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)
    
    print("Preview of extracted clinical features:")
    print(preview_df(clinical_df))
    
    # Save clinical data
    clinical_df.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 '2315554', '2315633', these appear to be probe IDs
# rather than human gene symbols. Gene symbols would typically be like 'BRCA1', 'TP53' etc.
# Therefore these IDs 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))
# 1. The 'ID' column in annotation matches probe IDs in expression data
# The 'gene_assignment' column contains gene symbols in format "symbol // description"
prob_col = 'ID'
gene_col = 'gene_assignment'

# 2. Get mapping between probe IDs and gene symbols
mapping_df = get_gene_mapping(gene_annotation, prob_col, gene_col)

# 3. Apply mapping to convert probe data to gene expression data
gene_data = apply_gene_mapping(genetic_data, mapping_df)

# Preview result
print("Gene expression data shape:", gene_data.shape)
print("\nFirst few gene symbols:")
print(list(gene_data.index)[:10])
print("\nFirst few expression values:")
print(gene_data.head())
# 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)