# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Rheumatoid_Arthritis"
cohort = "GSE176440"

# Input paths
in_trait_dir = "../DATA/GEO/Rheumatoid_Arthritis"
in_cohort_dir = "../DATA/GEO/Rheumatoid_Arthritis/GSE176440"

# Output paths
out_data_file = "./output/preprocess/3/Rheumatoid_Arthritis/GSE176440.csv"
out_gene_data_file = "./output/preprocess/3/Rheumatoid_Arthritis/gene_data/GSE176440.csv"
out_clinical_data_file = "./output/preprocess/3/Rheumatoid_Arthritis/clinical_data/GSE176440.csv"
json_path = "./output/preprocess/3/Rheumatoid_Arthritis/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")
# Check gene data availability - Yes, this is a microarray gene expression dataset
is_gene_available = True

# Check trait data availability - Feature 2 indicates treatment status, can be used for disease activity
trait_row = 2

# Age data is not available
age_row = None

# Gender data is not available
gender_row = None

# Convert treatment status to binary (before=1 active disease, after=0 controlled)
def convert_trait(value):
    if not isinstance(value, str):
        return None
    value = value.split(": ")[-1].lower()
    if "before" in value:
        return 1
    elif "after" in value:
        return 0
    return None

# Age conversion not needed
convert_age = None

# Gender conversion not needed  
convert_gender = None

# Validate and save cohort info
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 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 processed clinical data
print("Preview of clinical features:")
print(preview_df(clinical_features))

# Save clinical features
clinical_features.to_csv(out_clinical_data_file)
# Get file paths
soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)

# 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)
# Based on the probe IDs (e.g., A_23_P100001), these are Agilent microarray probe IDs, not gene symbols
# Therefore we need to map them to standard gene symbols
requires_gene_mapping = True
# Extract gene annotation data
gene_metadata = get_gene_annotation(soft_file)

# Preview the annotation data 
print("Column names:", gene_metadata.columns.tolist())
print("\nFirst few rows preview:")
print(preview_df(gene_metadata))
# Get gene mapping from annotation data
# ID column contains the same probe IDs as in gene expression data
# GENE_SYMBOL column contains the target gene symbols
mapping_data = get_gene_mapping(gene_metadata, prob_col='ID', gene_col='GENE_SYMBOL')

# Apply gene mapping to convert probe data to gene expression data
gene_data = apply_gene_mapping(gene_data, mapping_data)

# Preview the gene-level expression data
print("Shape of gene expression data after mapping:", gene_data.shape)
print("\nFirst few rows of gene-level data:")
print(gene_data.head())
print("\nFirst 20 gene symbols:")
print(gene_data.index[:20])
# 1. Normalize gene symbols
gene_data = normalize_gene_symbols_in_index(gene_data)
gene_data.to_csv(out_gene_data_file)

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

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

# 4. Check for bias  
trait_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=trait_biased,
    df=linked_data,
    note="Study examining transcriptome profiles in rheumatoid arthritis."
)

# 6. Save if usable
if is_usable:
    linked_data.to_csv(out_data_file)