simson_modeling/moleculenet_eval/better_eval.py

import pandas as pd
import numpy as np
import torch
import torch.nn as nn
import torch.optim as optim
from torch.utils.data import Dataset, DataLoader
from transformers import BertConfig, BertModel, AutoTokenizer
from rdkit import Chem, RDLogger
from rdkit.Chem.Scaffolds import MurckoScaffold
import copy
from tqdm import tqdm
import os
from sklearn.metrics import roc_auc_score, root_mean_squared_error, mean_absolute_error
from itertools import compress
from collections import defaultdict
from sklearn.metrics.pairwise import cosine_similarity
from sklearn.preprocessing import StandardScaler, MinMaxScaler
import optuna
import warnings
warnings.filterwarnings("ignore")
RDLogger.DisableLog('rdApp.*')

torch.set_float32_matmul_precision('high')

# --- 0. Pre-computed Contrastive SMILES Dataset ---
class PrecomputedContrastiveSmilesDataset(Dataset):
    """
    A Dataset class that reads pre-augmented SMILES pairs from a Parquet file.
    This is significantly faster as it offloads the expensive SMILES randomization
    to a one-time preprocessing step.
    """
    def __init__(self, tokenizer, file_path: str, max_length: int = 512):
        self.tokenizer = tokenizer
        self.max_length = max_length
        
        # Load the entire dataset from the Parquet file into memory.
        # This is fast and efficient for subsequent access.
        print(f"Loading pre-computed data from {file_path}...")
        self.data = pd.read_parquet(file_path)
        print("Data loaded successfully.")

    def __len__(self):
        """Returns the total number of pairs in the dataset."""
        return len(self.data)

    def __getitem__(self, idx):
        """
        Retrieves a pre-augmented pair, tokenizes it, and returns it
        in the format expected by the DataCollator.
        """
        # Retrieve the pre-augmented pair from the DataFrame
        row = self.data.iloc[idx]
        smiles_1 = row['smiles_1']
        smiles_2 = row['smiles_2']
        
        # Tokenize the pair. This operation is fast and remains in the data loader.
        tokens_1 = self.tokenizer(smiles_1, max_length=self.max_length, truncation=True, padding='max_length')
        tokens_2 = self.tokenizer(smiles_2, max_length=self.max_length, truncation=True, padding='max_length')
        
        return {
            'input_ids_1': torch.tensor(tokens_1['input_ids']),
            'attention_mask_1': torch.tensor(tokens_1['attention_mask']),
            'input_ids_2': torch.tensor(tokens_2['input_ids']),
            'attention_mask_2': torch.tensor(tokens_2['attention_mask']),
        }

# --- 0a. SMILES enumeration for preprocessing ---
class SmilesEnumerator:
    """Generates randomized SMILES strings for data augmentation."""
    def randomize_smiles(self, smiles):
        try:
            mol = Chem.MolFromSmiles(smiles)
            return Chem.MolToSmiles(mol, doRandom=True, canonical=False) if mol else smiles
        except:
            return smiles

def compute_embedding_similarity_precomputed(encoder, dataset, device):
    """
    Compute embedding similarity using pre-computed augmented SMILES pairs
    """
    encoder.eval()
    similarities = []
    
    dataloader = DataLoader(dataset, batch_size=32, shuffle=False)
    
    with torch.no_grad():
        for batch in dataloader:
            input_ids_1 = batch['input_ids_1'].to(device)
            attention_mask_1 = batch['attention_mask_1'].to(device)
            input_ids_2 = batch['input_ids_2'].to(device)
            attention_mask_2 = batch['attention_mask_2'].to(device)
            
            emb_1 = encoder(input_ids_1, attention_mask_1).cpu().numpy()
            emb_2 = encoder(input_ids_2, attention_mask_2).cpu().numpy()
            
            # Compute cosine similarity for each pair in the batch
            batch_similarities = []
            for i in range(len(emb_1)):
                sim = cosine_similarity([emb_1[i]], [emb_2[i]])[0][0]
                batch_similarities.append(sim)
            
            similarities.extend(batch_similarities)
    
    return np.array(similarities)

def create_augmented_smiles_file(smiles_list, output_path, num_augmentations=1):
    """
    Create a parquet file with pre-computed augmented SMILES pairs
    """
    enumerator = SmilesEnumerator()
    pairs = []
    
    print(f"Generating {num_augmentations} augmentations for {len(smiles_list)} SMILES...")
    
    for smiles in tqdm(smiles_list):
        for _ in range(num_augmentations):
            augmented = enumerator.randomize_smiles(smiles)
            pairs.append({
                'smiles_1': smiles,
                'smiles_2': augmented
            })
    
    df = pd.DataFrame(pairs)
    df.to_parquet(output_path, index=False)
    print(f"Saved {len(pairs)} augmented pairs to {output_path}")
    return output_path

# --- 1. Data Loading ---
def load_lists_from_url(data):
    # Datasets and their splits, all configurations carried over
    if data == 'bbbp':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/BBBP.csv')
        smiles, labels = df.smiles, df.p_np
    elif data == 'clintox':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/clintox.csv.gz', compression='gzip')
        smiles = df.smiles
        labels = df.drop(['smiles'], axis=1)
    elif data == 'hiv':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/HIV.csv')
        smiles, labels = df.smiles, df.HIV_active
    elif data == 'sider':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/sider.csv.gz', compression='gzip')
        smiles = df.smiles
        labels = df.drop(['smiles'], axis=1)
    elif data == 'esol':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/delaney-processed.csv')
        smiles = df.smiles
        labels = df['ESOL predicted log solubility in mols per litre']
    elif data == 'freesolv':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/SAMPL.csv')
        smiles = df.smiles
        labels = df.calc
    elif data == 'lipophicility':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/Lipophilicity.csv')
        smiles, labels = df.smiles, df['exp']
    elif data == 'tox21':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/tox21.csv.gz', compression='gzip')
        df = df.dropna(axis=0, how='any').reset_index(drop=True)
        smiles = df.smiles
        labels = df.drop(['mol_id', 'smiles'], axis=1)
    elif data == 'bace':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/bace.csv')
        smiles, labels = df.mol, df.Class
    elif data == 'qm8':
        df = pd.read_csv('https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/qm8.csv')
        df = df.dropna(axis=0, how='any').reset_index(drop=True)
        smiles = df.smiles
        labels = df.drop(['smiles', 'E2-PBE0.1', 'E1-PBE0.1', 'f1-PBE0.1', 'f2-PBE0.1'], axis=1)
    return smiles, labels

# --- 2. Scaffold Splitting ---
class ScaffoldSplitter:
    def __init__(self, data, seed, train_frac=0.8, val_frac=0.1, test_frac=0.1, include_chirality=True):
        self.data = data
        self.seed = seed
        self.include_chirality = include_chirality
        self.train_frac = train_frac
        self.val_frac = val_frac
        self.test_frac = test_frac

    def generate_scaffold(self, smiles):
        mol = Chem.MolFromSmiles(smiles)
        scaffold = MurckoScaffold.MurckoScaffoldSmiles(mol=mol, includeChirality=self.include_chirality)
        return scaffold

    def scaffold_split(self):
        smiles, labels = load_lists_from_url(self.data)
        non_null = np.ones(len(smiles)) == 0

        if self.data in {'tox21', 'sider', 'clintox'}:
            for i in range(len(smiles)):
                if Chem.MolFromSmiles(smiles[i]) and labels.loc[i].isnull().sum() == 0:
                    non_null[i] = 1
        else:
            for i in range(len(smiles)):
                if Chem.MolFromSmiles(smiles[i]):
                    non_null[i] = 1

        smiles_list = list(compress(enumerate(smiles), non_null))
        rng = np.random.RandomState(self.seed)

        scaffolds = defaultdict(list)
        for i, sms in smiles_list:
            scaffold = self.generate_scaffold(sms)
            scaffolds[scaffold].append(i)

        scaffold_sets = list(scaffolds.values())
        rng.shuffle(scaffold_sets)
        n_total_val = int(np.floor(self.val_frac * len(smiles_list)))
        n_total_test = int(np.floor(self.test_frac * len(smiles_list)))
        train_idx, val_idx, test_idx = [], [], []

        for scaffold_set in scaffold_sets:
            if len(val_idx) + len(scaffold_set) <= n_total_val:
                val_idx.extend(scaffold_set)
            elif len(test_idx) + len(scaffold_set) <= n_total_test:
                test_idx.extend(scaffold_set)
            else:
                train_idx.extend(scaffold_set)
        return train_idx, val_idx, test_idx

# --- 2a. Normal Random Split ---
def random_split_indices(n, seed=42, train_frac=0.8, val_frac=0.1, test_frac=0.1):
    np.random.seed(seed)
    indices = np.random.permutation(n)
    n_train = int(n * train_frac)
    n_val = int(n * val_frac)
    train_idx = indices[:n_train]
    val_idx = indices[n_train:n_train+n_val]
    test_idx = indices[n_train+n_val:]
    return train_idx.tolist(), val_idx.tolist(), test_idx.tolist()

# --- 3. PyTorch Dataset ---
class MoleculeDataset(Dataset):
    def __init__(self, smiles_list, labels, tokenizer, max_len=512):
        self.smiles_list = smiles_list
        self.labels = labels
        self.tokenizer = tokenizer
        self.max_len = max_len

    def __len__(self):
        return len(self.smiles_list)

    def __getitem__(self, idx):
        smiles = self.smiles_list[idx]
        label = self.labels.iloc[idx]

        encoding = self.tokenizer(
            smiles,
            truncation=True,
            padding='max_length',
            max_length=self.max_len,
            return_tensors='pt'
        )
        item = {key: val.squeeze(0) for key, val in encoding.items()}
        if isinstance(label, pd.Series):
            label_values = label.values.astype(np.float32)
        else:
            label_values = np.array([label], dtype=np.float32)
        item['labels'] = torch.tensor(label_values, dtype=torch.float)
        return item

# --- 4. Model Architecture ---
def global_ap(x):
    return torch.mean(x.view(x.size(0), x.size(1), -1), dim=1)

class SimSonEncoder(nn.Module):
    def __init__(self, config: BertConfig, max_len: int, dropout: float = 0.1):
        super(SimSonEncoder, self).__init__()
        self.config = config
        self.max_len = max_len
        self.bert = BertModel(config, add_pooling_layer=False)
        self.linear = nn.Linear(config.hidden_size, max_len)
        self.dropout = nn.Dropout(dropout)
    def forward(self, input_ids, attention_mask=None):
        if attention_mask is None:
            attention_mask = input_ids.ne(self.config.pad_token_id)
        outputs = self.bert(input_ids=input_ids, attention_mask=attention_mask)
        hidden_states = self.dropout(outputs.last_hidden_state)
        pooled = global_ap(hidden_states)
        return self.linear(pooled)

class SimSonClassifier(nn.Module):
    def __init__(self, encoder: SimSonEncoder, num_labels: int, dropout=0.1):
        super(SimSonClassifier, self).__init__()
        self.encoder = encoder
        self.clf = nn.Linear(encoder.max_len, num_labels)
        self.relu = nn.ReLU()
        self.dropout = nn.Dropout(dropout)
    def forward(self, input_ids, attention_mask=None):
        x = self.encoder(input_ids, attention_mask)
        x = self.relu(self.dropout(x))
        logits = self.clf(x)
        return logits

    def load_encoder_params(self, state_dict_path):
        self.encoder.load_state_dict(torch.load(state_dict_path))

# --- 5. Training, Validation, and Testing Loops ---
def get_criterion(task_type, num_labels):
    if task_type == 'classification':
        return nn.BCEWithLogitsLoss()
    elif task_type == 'regression':
        return nn.MSELoss()
    else:
        raise ValueError(f"Unknown task type: {task_type}")

def train_epoch(model, dataloader, optimizer, scheduler, criterion, device):
    model.train()
    total_loss = 0
    for batch in dataloader:
        inputs = {k: v.to(device) for k, v in batch.items() if k != 'labels'}
        labels = batch['labels'].to(device)
        optimizer.zero_grad()
        outputs = model(**inputs)
        loss = criterion(outputs, labels)
        loss.backward()
        optimizer.step()
        if scheduler is not None:
            scheduler.step()
        total_loss += loss.item()
    return total_loss / len(dataloader)

def calc_val_metrics(model, dataloader, criterion, device, task_type):
    model.eval()
    all_labels, all_preds = [], []
    total_loss = 0
    with torch.no_grad():
        for batch in dataloader:
            inputs = {k: v.to(device) for k, v in batch.items() if k != 'labels'}
            labels = batch['labels'].to(device)
            outputs = model(**inputs)
            loss = criterion(outputs, labels)
            total_loss += loss.item()
            if task_type == 'classification':
                pred_probs = torch.sigmoid(outputs).cpu().numpy()
                all_preds.append(pred_probs)
                all_labels.append(labels.cpu().numpy())
            else:
                # Regression
                preds = outputs.cpu().numpy()
                all_preds.append(preds)
                all_labels.append(labels.cpu().numpy())
    avg_loss = total_loss / len(dataloader)
    if task_type == 'classification':
        y_true = np.concatenate(all_labels)
        y_pred = np.concatenate(all_preds)
        try:
            score = roc_auc_score(y_true, y_pred, average='macro')
        except Exception:
            score = 0.0
        return avg_loss, score
    else:
        return avg_loss, None

def test_model(model, dataloader, device, task_type):
    model.eval()
    all_preds, all_labels = [], []
    with torch.no_grad():
        for batch in dataloader:
            inputs = {k: v.to(device) for k, v in batch.items() if k != 'labels'}
            labels = batch['labels']
            outputs = model(**inputs)
            if task_type == 'classification':
                preds = torch.sigmoid(outputs)
            else:
                preds = outputs
            all_preds.append(preds.cpu().numpy())
            all_labels.append(labels.numpy())
    return np.concatenate(all_preds), np.concatenate(all_labels)

# --- 6. Optuna Objective Function ---
def create_objective(name, info, train_smiles, train_labels, val_smiles, val_labels, 
                    test_smiles, test_labels, scaler, tokenizer, encoder_config, device):
    """Creates objective function for Optuna optimization"""
    
    def objective(trial):
        # Suggest hyperparameters
        lr = trial.suggest_float('lr', 1e-6, 1e-4, log=True)
        batch_size = trial.suggest_categorical('batch_size', [16, 32, 64, 128, 256])
        dropout = trial.suggest_float('dropout', 0.1, 0.5)
        weight_decay = trial.suggest_float('weight_decay', 0.0, 0.1)
        scheduler_type = trial.suggest_categorical('scheduler', ['plateau', 'cosine', 'step'])
        
        # Additional hyperparameters for optimization
        patience_lr = trial.suggest_int('patience_lr', 3, 10)
        gamma = trial.suggest_float('gamma', 0.5, 0.9) if scheduler_type == 'step' else 0.1
        
        try:
            # Create datasets and dataloaders
            train_dataset = MoleculeDataset(train_smiles, train_labels, tokenizer, 512)
            val_dataset = MoleculeDataset(val_smiles, val_labels, tokenizer, 512)
            test_dataset = MoleculeDataset(test_smiles, test_labels, tokenizer, 512)
            
            train_loader = DataLoader(train_dataset, batch_size=batch_size, shuffle=True)
            val_loader = DataLoader(val_dataset, batch_size=batch_size, shuffle=False)
            test_loader = DataLoader(test_dataset, batch_size=batch_size, shuffle=False)

            # Create model
            encoder = SimSonEncoder(encoder_config, 512, dropout=dropout)
            encoder = torch.compile(encoder)
            model = SimSonClassifier(encoder, num_labels=info['num_labels'], dropout=dropout).to(device)
            model.load_encoder_params('../simson_checkpoints/checkpoint_best_model.bin')

            criterion = get_criterion(info['task_type'], info['num_labels'])
            optimizer = optim.Adam(model.parameters(), lr=lr, weight_decay=weight_decay)
            
            # Create scheduler based on trial suggestion
            if scheduler_type == 'plateau':
                scheduler = optim.lr_scheduler.ReduceLROnPlateau(
                    optimizer, mode='max', factor=gamma, patience=patience_lr
                )
            elif scheduler_type == 'cosine':
                scheduler = optim.lr_scheduler.CosineAnnealingLR(optimizer, T_max=50)
            else:  # step
                scheduler = optim.lr_scheduler.StepLR(optimizer, step_size=10, gamma=gamma)

            # Training loop
            best_val_metric = -np.inf
            patience_counter = 0
            patience = 15
            
            for epoch in range(50):  # Max epochs
                train_loss = train_epoch(model, train_loader, optimizer, 
                                       scheduler if scheduler_type == 'cosine' else None, 
                                       criterion, device)
                val_loss, val_metric = calc_val_metrics(model, val_loader, criterion, device, info['task_type'])
                
                # Update scheduler
                if scheduler_type == 'plateau':
                    scheduler.step(val_loss if val_loss is not None else -val_loss)
                elif scheduler_type == 'step':
                    scheduler.step()
                
                # Determine metric to optimize
                if info['task_type'] == 'classification':
                    current_metric = val_loss if val_loss is not None else 0.0
                else:
                    current_metric = -val_loss  # For regression, minimize loss

                # Early stopping and best model tracking
                if current_metric <= val_loss:
                    best_val_metric = current_metric
                    patience_counter = 0
                else:
                    patience_counter += 1
                    if patience_counter >= patience:
                        break

                # Optuna pruning
                trial.report(current_metric, epoch)
                if trial.should_prune():
                    raise optuna.TrialPruned()

            return best_val_metric
            
        except Exception as e:
            print(f"Trial failed with error: {e}")
            return -np.inf  # Return worst possible score for failed trials
    
    return objective

# --- 7. Main Execution Block ---
def main():
    DEVICE = torch.device('cuda' if torch.cuda.is_available() else 'cpu')
    print(f"Using device: {DEVICE}")

    DATASETS_TO_RUN = {
        #'esol': {'task_type': 'regression', 'num_labels': 1, 'split': 'random'},
        # Add more datasets here, e.g. 'bbbp': {'task_type': 'classification', 'num_labels': 1, 'split': 'random'},
        #'sider': {'task_type': 'classification', 'num_labels': 27, 'split': 'random'},
        #'bace': {'task_type': 'classification', 'num_labels': 1, 'split': 'random'},
        'clintox': {'task_type': 'classification', 'num_labels': 2, 'split': 'scaffold'},
        'tox21': {'task_type': 'classification', 'num_labels': 12, 'split': 'random'},
        'bbbp': {'task_type': 'classification', 'num_labels': 1, 'split': 'scaffold'},
        'hiv': {'task_type': 'classification', 'num_labels': 1, 'split': 'scaffold'},
    }
    
    MAX_LEN = 512
    N_TRIALS = 100  # Number of Optuna trials to run
    
    TOKENIZER = AutoTokenizer.from_pretrained('DeepChem/ChemBERTa-77M-MTR')
    ENCODER_CONFIG = BertConfig(
        vocab_size=TOKENIZER.vocab_size,
        hidden_size=768,
        num_hidden_layers=4,
        num_attention_heads=12,
        intermediate_size=2048,
        max_position_embeddings=512
    )

    aggregated_results = {}

    for name, info in DATASETS_TO_RUN.items():
        print(f"\n{'='*20} Processing Dataset: {name.upper()} ({info['split']} split) {'='*20}")
        smiles, labels = load_lists_from_url(name)

        # For regression tasks, scale labels and remember scaling transform
        scaler = None
        if info["task_type"] == "regression":
            scaler = StandardScaler()
            all_labels = labels.values.reshape(-1, 1)
            scaler.fit(all_labels)
            labels = pd.Series(scaler.transform(all_labels).flatten(), index=labels.index)

        # Data split
        if info.get('split', 'scaffold') == 'scaffold':
            splitter = ScaffoldSplitter(data=name, seed=42)
            train_idx, val_idx, test_idx = splitter.scaffold_split()
        elif info['split'] == 'random':
            train_idx, val_idx, test_idx = random_split_indices(len(smiles), seed=42)
        else:
            raise ValueError(f"Unknown split type for {name}: {info['split']}")

        train_smiles = smiles.iloc[train_idx].reset_index(drop=True)
        train_labels = labels.iloc[train_idx].reset_index(drop=True)
        val_smiles = smiles.iloc[val_idx].reset_index(drop=True)
        val_labels = labels.iloc[val_idx].reset_index(drop=True)
        test_smiles = smiles.iloc[test_idx].reset_index(drop=True)
        test_labels = labels.iloc[test_idx].reset_index(drop=True)
        print(f"Data split - Train: {len(train_smiles)}, Val: {len(val_smiles)}, Test: {len(test_smiles)}")

        # Create Optuna study
        study = optuna.create_study(
            direction='maximize',
            pruner=optuna.pruners.MedianPruner(n_startup_trials=5, n_warmup_steps=10)
        )
        
        # Create objective function
        objective_func = create_objective(
            name, info, train_smiles, train_labels, val_smiles, val_labels,
            test_smiles, test_labels, scaler, TOKENIZER, ENCODER_CONFIG, DEVICE
        )
        
        # Run optimization
        print(f"Starting Optuna optimization with {N_TRIALS} trials...")
        study.optimize(objective_func, n_trials=N_TRIALS, timeout=None)
        
        # Get best parameters
        best_params = study.best_params
        best_score = study.best_value
        print(f"Best parameters: {best_params}")
        print(f"Best validation score: {0:.4f}")
        
        # Train final model with best parameters
        print("Training final model with best parameters...")
        train_dataset = MoleculeDataset(train_smiles, train_labels, TOKENIZER, MAX_LEN)
        val_dataset = MoleculeDataset(val_smiles, val_labels, TOKENIZER, MAX_LEN)
        test_dataset = MoleculeDataset(test_smiles, test_labels, TOKENIZER, MAX_LEN)
        
        train_loader = DataLoader(train_dataset, batch_size=best_params['batch_size'], shuffle=True)
        val_loader = DataLoader(val_dataset, batch_size=best_params['batch_size'], shuffle=False)
        test_loader = DataLoader(test_dataset, batch_size=best_params['batch_size'], shuffle=False)

        # Final model training
        encoder = SimSonEncoder(ENCODER_CONFIG, 512, dropout=best_params['dropout'])
        encoder = torch.compile(encoder)
        model = SimSonClassifier(encoder, num_labels=info['num_labels'], dropout=best_params['dropout']).to(DEVICE)
        model.load_encoder_params('../simson_checkpoints/checkpoint_best_model.bin')

        criterion = get_criterion(info['task_type'], info['num_labels'])
        optimizer = optim.Adam(model.parameters(), lr=best_params['lr'], weight_decay=best_params['weight_decay'])
        
        # Set up best scheduler
        if best_params['scheduler'] == 'plateau':
            scheduler = optim.lr_scheduler.ReduceLROnPlateau(
                optimizer, mode='max', factor=best_params.get('gamma', 0.7), 
                patience=best_params.get('patience_lr', 5)
            )
        elif best_params['scheduler'] == 'cosine':
            scheduler = optim.lr_scheduler.CosineAnnealingLR(optimizer, T_max=50)
        else:
            scheduler = optim.lr_scheduler.StepLR(optimizer, step_size=10, gamma=best_params.get('gamma', 0.1))

        # Train with best parameters
        best_val_metric = -np.inf
        best_model_state = None
        patience_counter = 0
        patience = 15
        
        for epoch in range(50):
            train_loss = train_epoch(model, train_loader, optimizer, 
                                   scheduler if best_params['scheduler'] == 'cosine' else None, 
                                   criterion, DEVICE)
            val_loss, val_metric = calc_val_metrics(model, val_loader, criterion, DEVICE, info['task_type'])
            
            if best_params['scheduler'] == 'plateau':
                scheduler.step(val_loss if val_loss is not None else -val_loss)
            elif best_params['scheduler'] == 'step':
                scheduler.step()
            
            if info['task_type'] == 'classification':
                print(f"Epoch {epoch+1}/50 | Train Loss: {train_loss:.4f} | Val Loss: {val_loss:.4f} | ROC AUC: {val_metric:.4f}")
                current_metric = val_metric if val_metric is not None else 0.0
            else:
                print(f"Epoch {epoch+1}/50 | Train Loss: {train_loss:.4f} | Val Loss: {val_loss:.4f}")
                current_metric = -val_loss

            if current_metric <= val_loss:
                best_val_metric = current_metric
                best_model_state = copy.deepcopy(model.state_dict())
                patience_counter = 0
            else:
                patience_counter += 1
                if patience_counter >= patience:
                    print(f'Early stopping at epoch {epoch+1}')
                    break

        # Test final model
        if best_model_state is not None:
            model.load_state_dict(best_model_state)
        
        test_preds, test_true = test_model(model, test_loader, DEVICE, info['task_type'])
        
        # Calculate final metrics
        if info['task_type'] == 'regression' and scaler is not None:
            test_preds = scaler.inverse_transform(test_preds.reshape(-1, 1)).flatten()
            test_true = scaler.inverse_transform(test_true.reshape(-1, 1)).flatten()
            rmse = root_mean_squared_error(test_true, test_preds)
            mae = mean_absolute_error(test_true, test_preds)
            final_score = -rmse
            print(f"Test RMSE: {rmse:.4f}, MAE: {mae:.4f}")
        else:
            try:
                final_score = roc_auc_score(test_true, test_preds, average='macro')
                print(f"Test ROC AUC: {final_score:.4f}")
            except Exception:
                final_score = 0.0

        # Compute embedding similarity using pre-computed augmented SMILES
        print("Creating pre-computed augmented SMILES for similarity computation...")
        test_smiles_list = list(test_smiles)
        similarity_file_path = f"{name}_test_augmented.parquet"
        create_augmented_smiles_file(test_smiles_list, similarity_file_path, num_augmentations=1)
        
        # Load pre-computed dataset for similarity computation
        similarity_dataset = PrecomputedContrastiveSmilesDataset(
            TOKENIZER, similarity_file_path, max_length=MAX_LEN
        )
        
        similarities = compute_embedding_similarity_precomputed(
            model.encoder, similarity_dataset, DEVICE
        )
        print(f"Similarity score: {similarities.mean():.4f}")
        
        # Clean up temporary file
        if os.path.exists(similarity_file_path):
            os.remove(similarity_file_path)

        aggregated_results[name] = {
            'best_score': final_score,
            'best_params': best_params,
            'optuna_trials': len(study.trials),
            'study': study,
            'similarity_score': similarities.mean()
        }

        if name == 'do_not_save':
            torch.save(model.encoder.state_dict(), 'moleculenet_clintox_encoder.bin')

    print(f"\n{'='*20} AGGREGATED RESULTS {'='*20}")
    for name, result in aggregated_results.items():
        print(f"{name}: Best score: {result['best_score']:.4f}")
        print(f"  Best parameters: {result['best_params']}")
        print(f"  Total trials: {result['optuna_trials']}")
        print(f"  Similarity score: {result['similarity_score']:.4f}")

    print("\nScript finished.")

if __name__ == '__main__':
    main()