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import sys
import os
sys.path.append('/home/st512/peptune/scripts/peptide-mdlm-mcts')
import xgboost as xgb
import torch
import numpy as np
import warnings
import numpy as np
from rdkit import Chem, rdBase, DataStructs
from transformers import AutoTokenizer, EsmModel

rdBase.DisableLog('rdApp.error')
warnings.filterwarnings("ignore", category=DeprecationWarning)
warnings.filterwarnings("ignore", category=UserWarning)
warnings.filterwarnings("ignore", category=FutureWarning)


class Hemolysis:
    def __init__(self):
        # change model path
        self.predictor = xgb.Booster(model_file='/home/tc415/flow_matching/classifier_ckpt/best_model_hemolysis.json')
        
        # Load ESM model and tokenizer
        self.tokenizer = AutoTokenizer.from_pretrained("facebook/esm2_t33_650M_UR50D")
        self.model = EsmModel.from_pretrained("facebook/esm2_t33_650M_UR50D")
        self.model.eval()
    
    def generate_embeddings(self, sequences):
        """Generate ESM embeddings for protein sequences"""
        embeddings = []
        
        # Process sequences in batches to avoid memory issues
        batch_size = 8
        for i in range(0, len(sequences), batch_size):
            batch_sequences = sequences[i:i + batch_size]
            
            inputs = self.tokenizer(
                batch_sequences, 
                padding=True, 
                truncation=True, 
                return_tensors="pt"
            )
            
            if torch.cuda.is_available():
                inputs = {k: v.cuda() for k, v in inputs.items()}
                self.model = self.model.cuda()
            
            # Generate embeddings
            with torch.no_grad():
                outputs = self.model(**inputs)
                
                # Get last hidden states
                last_hidden_states = outputs.last_hidden_state
                # pdb.set_trace()
                # Compute mean pooling (excluding padding tokens)
                attention_mask = inputs['attention_mask'].unsqueeze(-1)
                masked_hidden_states = last_hidden_states * attention_mask
                sum_hidden_states = masked_hidden_states.sum(dim=1)
                seq_lengths = attention_mask.sum(dim=1)
                batch_embeddings = sum_hidden_states / seq_lengths
                
                batch_embeddings = batch_embeddings.cpu().numpy()
                embeddings.append(batch_embeddings)
        
        if embeddings:
            return np.vstack(embeddings)
        else:
            return np.array([])
    
    def get_scores(self, input_seqs: list):
        scores = np.ones(len(input_seqs))
        features = self.generate_embeddings(input_seqs)
        
        if len(features) == 0:
            return scores
        
        features = np.nan_to_num(features, nan=0.)
        features = np.clip(features, np.finfo(np.float32).min, np.finfo(np.float32).max)
        
        features = xgb.DMatrix(features)
        
        probs = self.predictor.predict(features)
        # return the probability of it being not hemolytic
        return scores - probs
    
    def __call__(self, input_seqs: list):
        scores = self.get_scores(input_seqs)
        return scores
    
def unittest():
    hemolysis = Hemolysis()
    sequences = [
        "MKTVRQERLKSIVRILERSKEPVSGAQLAEELSVSRQVIVQDIAYLRSLGYNIVATPRGYVLAGG",
        "MSEGIRQAFVLAKSIWPARVARFTVDNRIRSLVKTYEAIKVDPYNPAFLEVLD"
    ]    
    
    scores = hemolysis(input_seqs=sequences)
    print([1-score for score in scores])
    
if __name__ == '__main__':
    unittest()