# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Adrenocortical_Cancer"

# Input paths
tcga_root_dir = "../DATA/TCGA"

# Output paths
out_data_file = "./output/z1/preprocess/Adrenocortical_Cancer/TCGA.csv"
out_gene_data_file = "./output/z1/preprocess/Adrenocortical_Cancer/gene_data/TCGA.csv"
out_clinical_data_file = "./output/z1/preprocess/Adrenocortical_Cancer/clinical_data/TCGA.csv"
json_path = "./output/z1/preprocess/Adrenocortical_Cancer/cohort_info.json"


# Step 1: Initial Data Loading
import os
import pandas as pd

# Identify the most relevant TCGA cohort directory for the current trait
subdirs = [d for d in os.listdir(tcga_root_dir) if os.path.isdir(os.path.join(tcga_root_dir, d))]
target_keywords = ['adrenocortical', '(acc)']  # prioritize exact trait and abbreviation
matches = []
for d in subdirs:
    name = d.lower()
    score = 0
    if 'adrenocortical' in name:
        score += 2
    if '(acc)' in name or '_acc' in name:
        score += 1
    if score > 0:
        matches.append((score, d))

selected_dir = None
if matches:
    # Choose the highest score; if tie, the first one encountered
    matches.sort(key=lambda x: (-x[0], x[1]))
    selected_dir = matches[0][1]

# If no suitable directory is found, mark as completed for this trait and stop further processing
if selected_dir is None:
    validate_and_save_cohort_info(
        is_final=False,
        cohort="TCGA",
        info_path=json_path,
        is_gene_available=False,
        is_trait_available=False
    )
else:
    cohort_dir = os.path.join(tcga_root_dir, selected_dir)
    # Identify clinical and genetic file paths
    try:
        clinical_file_path, genetic_file_path = tcga_get_relevant_filepaths(cohort_dir)
    except Exception:
        # If file identification fails, mark as unavailable
        validate_and_save_cohort_info(
            is_final=False,
            cohort="TCGA",
            info_path=json_path,
            is_gene_available=False,
            is_trait_available=False
        )
    else:
        # Load clinical and genetic data
        clinical_df = pd.read_csv(clinical_file_path, sep='\t', index_col=0, compression='infer', low_memory=False)
        genetic_df = pd.read_csv(genetic_file_path, sep='\t', index_col=0, compression='infer', low_memory=False)
        # Print clinical column names
        print(clinical_df.columns.tolist())

# Step 2: Find Candidate Demographic Features
import os
import pandas as pd

# Try to use existing clinical_df; otherwise, attempt to load from TCGA ACC cohort
if 'clinical_df' not in globals():
    # Heuristic to locate ACC cohort directory
    acc_dir = os.path.join(tcga_root_dir, 'ACC')
    if not os.path.isdir(acc_dir):
        subdirs = [d for d in os.listdir(tcga_root_dir) if os.path.isdir(os.path.join(tcga_root_dir, d))]
        acc_candidates = [d for d in subdirs if 'ACC' in d.upper()]
        acc_dir = os.path.join(tcga_root_dir, acc_candidates[0]) if acc_candidates else None

    if acc_dir:
        try:
            clinical_file_path, _ = tcga_get_relevant_filepaths(acc_dir)
            clinical_df = pd.read_csv(clinical_file_path, sep='\t', index_col=0, dtype=str)
        except Exception:
            clinical_df = None
    else:
        clinical_df = None

available_cols = list(clinical_df.columns) if isinstance(clinical_df, pd.DataFrame) else []

def is_age_col(col: str) -> bool:
    c = col.lower()
    if 'stage' in c:  # avoid false positive from 'stage'
        return False
    if c.startswith('age') or 'age_' in c or '_age' in c or 'age at' in c:
        return True
    if 'days_to_birth' in c or 'birth' in c:
        return True
    return False

def is_gender_col(col: str) -> bool:
    c = col.lower().strip()
    if c in {'gender', 'sex'}:
        return True
    if c.startswith('gender') or c.endswith('_gender'):
        return True
    # Avoid false positive from strings containing 'sex' (e.g., 'excess')
    if c == 'sex':
        return True
    return False

candidate_age_cols = [c for c in available_cols if is_age_col(c)]
candidate_gender_cols = [c for c in available_cols if is_gender_col(c)]

print(f"candidate_age_cols = {candidate_age_cols}")
print(f"candidate_gender_cols = {candidate_gender_cols}")

# Preview extracted data if clinical_df is available and there are candidate columns
selected_cols = [c for c in (candidate_age_cols + candidate_gender_cols) if c in available_cols]
if isinstance(clinical_df, pd.DataFrame) and len(selected_cols) > 0:
    preview_dict = preview_df(clinical_df[selected_cols], n=5)
    print(preview_dict)
else:
    print({})

# Step 3: Select Demographic Features
import math

# Helper to check if a small list of preview values is usable (not mostly missing)
def _is_valid_preview(values, min_non_missing=3):
    if not isinstance(values, (list, tuple)) or len(values) == 0:
        return False
    def _is_missing(v):
        if v is None:
            return True
        if isinstance(v, float) and math.isnan(v):
            return True
        if isinstance(v, str) and v.strip() == "":
            return True
        return False
    non_missing = sum(0 if _is_missing(v) else 1 for v in values)
    return non_missing >= min_non_missing

# Try to locate the preview dictionaries created in prior steps
age_values_dict = {}
gender_values_dict = {}

# Known possible variable names
_possible_age_dict_names = ["age_values_dict", "age_preview_dict", "age_dict"]
_possible_gender_dict_names = ["gender_values_dict", "gender_preview_dict", "gender_dict"]

# Pull from known names if available
for _name in _possible_age_dict_names:
    try:
        _val = eval(_name)
        if isinstance(_val, dict):
            age_values_dict = _val
            break
    except NameError:
        pass

for _name in _possible_gender_dict_names:
    try:
        _val = eval(_name)
        if isinstance(_val, dict):
            gender_values_dict = _val
            break
    except NameError:
        pass

# If separate dicts not found, try to derive them from any combined dict present in the environment
if (not age_values_dict or not gender_values_dict):
    # Search for a dict with keys covering candidate columns
    try:
        # Collect candidate keys for age and gender
        age_keys = set(candidate_age_cols) if 'candidate_age_cols' in globals() else set()
        gender_keys = set(candidate_gender_cols) if 'candidate_gender_cols' in globals() else set()
        # Scan global namespace for any dict that might contain these keys
        for _var, _obj in list(globals().items()):
            if isinstance(_obj, dict):
                if not age_values_dict and age_keys and any(k in _obj for k in age_keys):
                    age_values_dict = {k: _obj[k] for k in age_keys if k in _obj}
                if not gender_values_dict and gender_keys and any(k in _obj for k in gender_keys):
                    gender_values_dict = {k: _obj[k] for k in gender_keys if k in _obj}
                if age_values_dict and gender_values_dict:
                    break
    except Exception:
        pass

# Initialize selections
age_col = None
gender_col = None

# Select age column with preference and validity checks
if isinstance(candidate_age_cols, (list, tuple)) and len(candidate_age_cols) > 0 and isinstance(age_values_dict, dict):
    # Filter to candidates that exist in the preview dict and look valid
    valid_age_candidates = [c for c in candidate_age_cols if c in age_values_dict and _is_valid_preview(age_values_dict.get(c, []))]
    # Apply preference: age_at_initial_pathologic_diagnosis > days_to_birth > first valid
    if 'age_at_initial_pathologic_diagnosis' in valid_age_candidates:
        age_col = 'age_at_initial_pathologic_diagnosis'
    elif 'days_to_birth' in valid_age_candidates:
        age_col = 'days_to_birth'
    elif valid_age_candidates:
        age_col = valid_age_candidates[0]

# Select gender column with validity checks
if isinstance(candidate_gender_cols, (list, tuple)) and len(candidate_gender_cols) > 0 and isinstance(gender_values_dict, dict):
    valid_gender_candidates = [c for c in candidate_gender_cols if c in gender_values_dict and _is_valid_preview(gender_values_dict.get(c, []))]
    if 'gender' in valid_gender_candidates:
        gender_col = 'gender'
    elif valid_gender_candidates:
        gender_col = valid_gender_candidates[0]

# If preview dicts are empty, set to None explicitly per instruction
if not isinstance(age_values_dict, dict) or len(age_values_dict) == 0:
    age_col = None
if not isinstance(gender_values_dict, dict) or len(gender_values_dict) == 0:
    gender_col = None

# Explicitly print out selected columns and their first 5 values (if available)
print(f"Selected age_col: {age_col}")
if age_col is not None and isinstance(age_values_dict, dict) and age_col in age_values_dict:
    print(f"age_col first5 values: {age_values_dict[age_col]}")
else:
    print("age_col first5 values: None")

print(f"Selected gender_col: {gender_col}")
if gender_col is not None and isinstance(gender_values_dict, dict) and gender_col in gender_values_dict:
    print(f"gender_col first5 values: {gender_values_dict[gender_col]}")
else:
    print("gender_col first5 values: None")

# Step 4: Feature Engineering and Validation
import os
import pandas as pd

# Ensure clinical_df and genetic_df are available (fallback to reload if needed)
if 'clinical_df' not in globals() or 'genetic_df' not in globals():
    # Locate ACC cohort directory
    subdirs = [d for d in os.listdir(tcga_root_dir) if os.path.isdir(os.path.join(tcga_root_dir, d))]
    acc_dir = None
    for d in subdirs:
        if 'adrenocortical_cancer_(acc)' in d.lower() or d.upper().endswith('(ACC)') or d.upper() == 'ACC':
            acc_dir = os.path.join(tcga_root_dir, d)
            break
    if acc_dir is None:
        # Worst-case, pick any directory containing ACC
        acc_candidates = [d for d in subdirs if 'ACC' in d.upper()]
        acc_dir = os.path.join(tcga_root_dir, acc_candidates[0]) if acc_candidates else None

    if acc_dir:
        clinical_file_path, genetic_file_path = tcga_get_relevant_filepaths(acc_dir)
        clinical_df = pd.read_csv(clinical_file_path, sep='\t', index_col=0, compression='infer', low_memory=False)
        genetic_df = pd.read_csv(genetic_file_path, sep='\t', index_col=0, compression='infer', low_memory=False)
    else:
        raise RuntimeError("ACC cohort directory not found; cannot proceed.")

# Use selected demographic columns from previous step; default to None if missing
age_col = age_col if 'age_col' in globals() else None
gender_col = gender_col if 'gender_col' in globals() else None

# 1) Extract and standardize clinical features (Trait, optional Age and Gender)
selected_clinical_df = tcga_select_clinical_features(
    clinical_df=clinical_df,
    trait=trait,
    age_col=age_col,
    gender_col=gender_col
)

# 2) Normalize gene symbols and save normalized gene expression
normalized_gene_df = normalize_gene_symbols_in_index(genetic_df.copy())
normalized_gene_df = normalized_gene_df.apply(pd.to_numeric, errors='coerce')

# Save normalized gene data
os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)
normalized_gene_df.to_csv(out_gene_data_file)

# 3) Link clinical and genetic data on sample IDs
expr_t = normalized_gene_df.T  # samples x genes
linked_data = selected_clinical_df.join(expr_t, how='inner')

# 4) Handle missing values systematically
processed_df = handle_missing_values(linked_data, trait_col=trait)

# 5) Determine bias in trait and demographic features; remove biased demographics
trait_biased, processed_df = judge_and_remove_biased_features(processed_df, trait)

# 6) Final validation and save cohort info
# Sanitize DataFrame to avoid potential non-JSON-serializable types from pandas index/columns
processed_df_safe = processed_df.copy()
processed_df_safe.index = processed_df_safe.index.astype(str)
processed_df_safe.columns = [str(c) for c in list(processed_df_safe.columns)]

covariate_cols = [trait, 'Age', 'Gender']
gene_cols_in_processed = [c for c in processed_df_safe.columns if c not in covariate_cols]
is_gene_available = bool(len(gene_cols_in_processed) > 0)
is_trait_available = bool((trait in processed_df_safe.columns) and processed_df_safe[trait].notna().any())

note_parts = [
    "INFO: TCGA ACC cohort processed; gene symbols normalized via NCBI synonyms.",
]
if age_col or gender_col:
    note_parts.append(f"INFO: Age from '{age_col if age_col else 'None'}', Gender from '{gender_col if gender_col else 'None'}'.")
if trait_biased:
    note_parts.append("WARNING: Trait is severely biased (likely no normal controls in ACC).")
note = " ".join(note_parts)

# Attempt validation; if serialization fails, retry after deeper sanitization
is_usable = False
try:
    is_usable = validate_and_save_cohort_info(
        is_final=True,
        cohort="TCGA",
        info_path=json_path,
        is_gene_available=is_gene_available,
        is_trait_available=is_trait_available,
        is_biased=bool(trait_biased),
        df=processed_df_safe,
        note=note
    )
except TypeError as e:
    # Deep sanitize: ensure Python-native types in a minimal copy of df metadata
    processed_df_safe2 = processed_df_safe.copy()
    processed_df_safe2.index = [str(x) for x in processed_df_safe2.index.tolist()]
    processed_df_safe2.columns = [str(x) for x in processed_df_safe2.columns.tolist()]
    try:
        is_usable = validate_and_save_cohort_info(
            is_final=True,
            cohort="TCGA",
            info_path=json_path,
            is_gene_available=bool(is_gene_available),
            is_trait_available=bool(is_trait_available),
            is_biased=bool(trait_biased),
            df=processed_df_safe2,
            note=note
        )
    except Exception as e2:
        # If still failing, do not raise to keep pipeline running; mark unusable in a minimal way
        is_usable = False

# 7) Save linked data only if usable
if is_usable:
    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
    processed_df_safe.to_csv(out_data_file)