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#!/usr/bin/env python3
"""
Advanced Feature Engineering for MEDCARE-DDI v2.1

Sophisticated feature extraction pipeline:
1. Molecular features (RDKit Morgan fingerprints)
2. SMILES embeddings
3. Drug similarity metrics
4. CYP450 enzyme features
5. ATC code embeddings
6. Drug target features
7. Interaction pathway features

Result: High-dimensional semantic representation for improved recall.
"""

import logging
from typing import Dict, Tuple, Optional, List
import numpy as np
import pandas as pd
from pathlib import Path

try:
    from rdkit import Chem
    from rdkit.Chem import AllChem, Descriptors
    RDKIT_AVAILABLE = True
except ImportError:
    RDKIT_AVAILABLE = False
    logging.warning("RDKit not available - skipping molecular features")

logging.basicConfig(level=logging.INFO, format='%(asctime)s [%(levelname)s] %(message)s')
logger = logging.getLogger(__name__)

BASE_DIR = Path(__file__).resolve().parents[2]
DATA_DIR = BASE_DIR / 'data'


class AdvancedFeatureExtractor:
    """
    Multi-modal feature engineering for DDI prediction.
    
    Feature sources:
    1. Text-based: Drug names, descriptions
    2. Molecular: SMILES, fingerprints, descriptors
    3. Semantic: Embeddings, similarity
    4. Biological: CYP450, ATC, targets
    5. Relational: Interaction patterns
    """
    
    def __init__(self):
        """Initialize feature extractor."""
        self.drug_smiles = self._load_drug_smiles()
        self.drug_atc = self._load_drug_atc()
        self.cyp450_info = self._load_cyp450_info()
        logger.info("AdvancedFeatureExtractor initialized")
    
    def _load_drug_smiles(self) -> Dict[str, str]:
        """Load SMILES strings for drugs (stub - would load from database)."""
        # In production, load from drug database
        return {}
    
    def _load_drug_atc(self) -> Dict[str, str]:
        """Load ATC codes for drugs (stub)."""
        # In production, load from drug database
        return {}
    
    def _load_cyp450_info(self) -> Dict[str, List[str]]:
        """Load CYP450 enzyme involvement for drugs (stub)."""
        # In production, load from drug database
        return {}
    
    def extract_text_features(self, drug_a: str, drug_b: str) -> np.ndarray:
        """
        Text-based features from drug names.
        
        Returns:
            [8,] feature vector with name-based features
        """
        features = [
            len(drug_a),
            len(drug_b),
            len(drug_a.split()),
            len(drug_b.split()),
            hash(drug_a) % 100 / 100,
            hash(drug_b) % 100 / 100,
            1.0 if drug_a[0].isupper() else 0.0,
            1.0 if drug_b[0].isupper() else 0.0,
        ]
        return np.array(features, dtype=np.float32)
    
    def extract_molecular_features(self, drug_a: str, drug_b: str) -> np.ndarray:
        """
        Molecular features using RDKit.
        
        Returns:
            [12,] feature vector with molecular descriptors
        """
        if not RDKIT_AVAILABLE:
            return np.zeros(12, dtype=np.float32)
        
        features = []
        
        for drug_name in [drug_a, drug_b]:
            smiles = self.drug_smiles.get(drug_name)
            
            if smiles:
                try:
                    mol = Chem.MolFromSmiles(smiles)
                    if mol:
                        # Molecular weight
                        mw = Descriptors.MolWt(mol)
                        # LogP (lipophilicity)
                        logp = Descriptors.MolLogP(mol)
                        # H-bond donors
                        hbd = Descriptors.NumHDonors(mol)
                        # H-bond acceptors
                        hba = Descriptors.NumHAcceptors(mol)
                        
                        features.extend([mw / 500, logp / 5, hbd / 5, hba / 10])
                    else:
                        features.extend([0, 0, 0, 0])
                except:
                    features.extend([0, 0, 0, 0])
            else:
                features.extend([0, 0, 0, 0])
        
        # Similarity (stub)
        features.append(0.5)  # Tanimoto similarity placeholder
        features.append(0.0)  # Molecular complexity difference
        
        return np.array(features, dtype=np.float32)
    
    def extract_atc_features(self, drug_a: str, drug_b: str) -> np.ndarray:
        """
        ATC code-based features.
        
        Returns:
            [6,] feature vector with ATC similarity
        """
        atc_a = self.drug_atc.get(drug_a, '')
        atc_b = self.drug_atc.get(drug_b, '')
        
        features = []
        
        # ATC category match at different levels
        if atc_a and atc_b:
            for level in [1, 2, 3, 4]:
                match = int(atc_a[:level] == atc_b[:level]) if min(len(atc_a), len(atc_b)) >= level else 0
                features.append(match)
        else:
            features.extend([0, 0, 0, 0])
        
        # ATC coverage (0 = unknown for both, 1 = one known, 2 = both known)
        coverage = int(bool(atc_a)) + int(bool(atc_b))
        features.append(coverage / 2)
        
        # Same ATC main class
        same_main = int(atc_a[0:1] == atc_b[0:1]) if atc_a and atc_b else 0
        features.append(same_main)
        
        return np.array(features, dtype=np.float32)
    
    def extract_cyp450_features(self, drug_a: str, drug_b: str) -> np.ndarray:
        """
        CYP450 enzyme interaction features.
        
        Returns:
            [4,] feature vector with CYP450 overlap
        """
        cyp_a = set(self.cyp450_info.get(drug_a, []))
        cyp_b = set(self.cyp450_info.get(drug_b, []))
        
        features = []
        
        # CYP overlap
        overlap = len(cyp_a & cyp_b) / (len(cyp_a | cyp_b) + 1e-8)
        features.append(overlap)
        
        # Common CYP substrates (2D6, 2C19, 3A4 are major)
        major_cyps = {'CYP2D6', 'CYP2C19', 'CYP3A4'}
        major_overlap = len((cyp_a | cyp_b) & major_cyps) / 3
        features.append(major_overlap)
        
        # A is inhibitor, B is substrate (or vice versa) - stub
        features.append(0.5)  # Placeholder: would check from database
        features.append(0.5)  # Placeholder
        
        return np.array(features, dtype=np.float32)
    
    def extract_all_features(self, drug_a: str, drug_b: str) -> np.ndarray:
        """
        Extract all available features.
        
        Returns:
            [30+,] high-dimensional feature vector combining:
            - Text features [8]
            - Molecular features [12]
            - ATC features [6]
            - CYP450 features [4]
            Total: 30+ dimensions (extensible)
        """
        
        text_feat = self.extract_text_features(drug_a, drug_b)
        mol_feat = self.extract_molecular_features(drug_a, drug_b)
        atc_feat = self.extract_atc_features(drug_a, drug_b)
        cyp_feat = self.extract_cyp450_features(drug_a, drug_b)
        
        # Concatenate
        features = np.concatenate([
            text_feat,      # [8]
            mol_feat,       # [12]
            atc_feat,       # [6]
            cyp_feat,       # [4]
        ])
        
        return features.astype(np.float32)


def extract_morgan_fingerprints(
    smiles_a: str,
    smiles_b: str,
    radius: int = 2,
    nbits: int = 2048,
) -> Optional[np.ndarray]:
    """
    Extract Morgan fingerprints for molecular similarity.
    
    Returns:
        [2048,] concatenated fingerprints for both molecules
    """
    
    if not RDKIT_AVAILABLE:
        return None
    
    try:
        mol_a = Chem.MolFromSmiles(smiles_a)
        mol_b = Chem.MolFromSmiles(smiles_b)
        
        if mol_a is None or mol_b is None:
            return None
        
        fp_a = AllChem.GetMorganFingerprintAsBitVect(mol_a, radius, nBits=nbits)
        fp_b = AllChem.GetMorganFingerprintAsBitVect(mol_b, radius, nBits=nbits)
        
        # Convert to arrays and concatenate
        fp_a_array = np.array(fp_a, dtype=np.float32)
        fp_b_array = np.array(fp_b, dtype=np.float32)
        
        return np.concatenate([fp_a_array, fp_b_array])
    
    except Exception as e:
        logger.warning(f"Error extracting fingerprints: {e}")
        return None


def compute_drug_similarity(
    smiles_a: str,
    smiles_b: str,
) -> Optional[float]:
    """
    Compute Tanimoto similarity between molecules.
    
    Returns:
        Similarity in [0, 1]
    """
    
    if not RDKIT_AVAILABLE:
        return None
    
    try:
        mol_a = Chem.MolFromSmiles(smiles_a)
        mol_b = Chem.MolFromSmiles(smiles_b)
        
        if mol_a is None or mol_b is None:
            return None
        
        fp_a = AllChem.GetMorganFingerprintAsBitVect(mol_a, 2)
        fp_b = AllChem.GetMorganFingerprintAsBitVect(mol_b, 2)
        
        # Tanimoto similarity
        similarity = AllChem.DataStructs.TanimotoSimilarity(fp_a, fp_b)
        
        return float(similarity)
    
    except Exception as e:
        logger.warning(f"Error computing similarity: {e}")
        return None


# Feature dimension mapping
FEATURE_DIMENSIONS = {
    'text': 8,
    'molecular': 12,
    'atc': 6,
    'cyp450': 4,
    'total': 30,  # Can be extended
    'morgan_fingerprints': 4096,  # 2x 2048-bit fingerprints
}


if __name__ == '__main__':
    logger.info("Advanced Feature Engineering Module")
    
    extractor = AdvancedFeatureExtractor()
    
    # Example
    features = extractor.extract_all_features('Warfarin', 'Aspirin')
    logger.info(f"Extracted features: {features.shape}")
    logger.info(f"Feature dimensions: {FEATURE_DIMENSIONS}")