init_code

mcd/metrics/abstract_metrics.py

@@ -0,0 +1,138 @@
+import torch
+from torch import Tensor
+from torch.nn import functional as F
+from torchmetrics import Metric, MeanSquaredError
+
+
+class TrainAbstractMetricsDiscrete(torch.nn.Module):
+    def __init__(self):
+        super().__init__()
+
+    def forward(self, masked_pred_X, masked_pred_E, true_X, true_E, log: bool):
+        pass
+
+    def reset(self):
+        pass
+
+    def log_epoch_metrics(self, current_epoch):
+        pass
+
+
+class TrainAbstractMetrics(torch.nn.Module):
+    def __init__(self):
+        super().__init__()
+
+    def forward(self, masked_pred_epsX, masked_pred_epsE, pred_y, true_epsX, true_epsE, true_y, log):
+        pass
+
+    def reset(self):
+        pass
+
+    def log_epoch_metrics(self, current_epoch):
+        pass
+
+
+class SumExceptBatchMetric(Metric):
+    def __init__(self):
+        super().__init__()
+        self.add_state('total_value', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+
+    def update(self, values) -> None:
+        self.total_value += torch.sum(values)
+        self.total_samples += values.shape[0]
+
+    def compute(self):
+        return self.total_value / self.total_samples
+
+
+class SumExceptBatchMSE(MeanSquaredError):
+    def update(self, preds: Tensor, target: Tensor) -> None:
+        """Update state with predictions and targets.
+
+        Args:
+            preds: Predictions from model
+            target: Ground truth values
+        """
+        assert preds.shape == target.shape
+        sum_squared_error, n_obs = self._mean_squared_error_update(preds, target)
+
+        self.sum_squared_error += sum_squared_error
+        self.total += n_obs
+
+    def _mean_squared_error_update(self, preds: Tensor, target: Tensor):
+            """ Updates and returns variables required to compute Mean Squared Error. Checks for same shape of input
+            tensors.
+                preds: Predicted tensor
+                target: Ground truth tensor
+            """
+            diff = preds - target
+            sum_squared_error = torch.sum(diff * diff)
+            n_obs = preds.shape[0]
+            return sum_squared_error, n_obs
+
+
+class SumExceptBatchKL(Metric):
+    def __init__(self):
+        super().__init__()
+        self.add_state('total_value', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+
+    def update(self, p, q) -> None:
+        self.total_value += F.kl_div(q, p, reduction='sum')
+        self.total_samples += p.size(0)
+
+    def compute(self):
+        return self.total_value / self.total_samples
+
+
+class CrossEntropyMetric(Metric):
+    def __init__(self):
+        super().__init__()
+        self.add_state('total_ce', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+
+    def update(self, preds: Tensor, target: Tensor, weight=None) -> None:
+        """ Update state with predictions and targets.
+            preds: Predictions from model   (bs * n, d) or (bs * n * n, d)
+            target: Ground truth values     (bs * n, d) or (bs * n * n, d). """
+        target = torch.argmax(target, dim=-1)
+        if weight is not None:
+            weight = weight.type_as(preds)
+            output = F.cross_entropy(preds, target, weight = weight, reduction='sum')
+        else:
+            output = F.cross_entropy(preds, target, reduction='sum')
+        self.total_ce += output
+        self.total_samples += preds.size(0)
+
+    def compute(self):
+        return self.total_ce / self.total_samples
+
+
+class ProbabilityMetric(Metric):
+    def __init__(self):
+        """ This metric is used to track the marginal predicted probability of a class during training. """
+        super().__init__()
+        self.add_state('prob', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total', default=torch.tensor(0.), dist_reduce_fx="sum")
+
+    def update(self, preds: Tensor) -> None:
+        self.prob += preds.sum()
+        self.total += preds.numel()
+
+    def compute(self):
+        return self.prob / self.total
+
+
+class NLL(Metric):
+    def __init__(self):
+        super().__init__()
+        self.add_state('total_nll', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+
+    def update(self, batch_nll) -> None:
+        self.total_nll += torch.sum(batch_nll)
+        self.total_samples += batch_nll.numel()
+
+    def compute(self):
+        return self.total_nll / self.total_samples

mcd/metrics/molecular_metrics_sampling.py

@@ -0,0 +1,138 @@
+### packages for visualization
+from analysis.rdkit_functions import compute_molecular_metrics
+from mini_moses.metrics.metrics import compute_intermediate_statistics
+from metrics.property_metric import TaskModel
+
+import torch
+import torch.nn as nn
+
+import os
+import csv
+import time
+
+def result_to_csv(path, dict_data):
+    file_exists = os.path.exists(path)
+    log_name = dict_data.pop("log_name", None)
+    if log_name is None:
+        raise ValueError("The provided dictionary must contain a 'log_name' key.")
+    field_names = ["log_name"] + list(dict_data.keys())
+    dict_data["log_name"] = log_name
+    with open(path, "a", newline="") as file:
+        writer = csv.DictWriter(file, fieldnames=field_names)
+        if not file_exists:
+            writer.writeheader()
+        writer.writerow(dict_data)
+
+
+class SamplingMolecularMetrics(nn.Module):
+    def __init__(
+        self,
+        dataset_infos,
+        train_smiles,
+        reference_smiles,
+        n_jobs=1,
+        device="cpu",
+        batch_size=512,
+    ):
+        super().__init__()
+        self.task_name = dataset_infos.task
+        self.dataset_infos = dataset_infos
+        self.active_atoms = dataset_infos.active_atoms
+        self.train_smiles = train_smiles
+
+        if reference_smiles is not None:
+            print(
+                f"--- Computing intermediate statistics for training for #{len(reference_smiles)} smiles ---"
+            )
+            start_time = time.time()
+            self.stat_ref = compute_intermediate_statistics(
+                reference_smiles, n_jobs=n_jobs, device=device, batch_size=batch_size
+            )
+            end_time = time.time()
+            elapsed_time = end_time - start_time
+            print(
+                f"--- End computing intermediate statistics: using {elapsed_time:.2f}s ---"
+            )
+        else:
+            self.stat_ref = None
+    
+        self.comput_config = {
+            "n_jobs": n_jobs,
+            "device": device,
+            "batch_size": batch_size,
+        }
+
+        self.task_evaluator = {'meta_taskname': dataset_infos.task, 'sas': None, 'scs': None}
+        for cur_task in dataset_infos.task.split("-")[:]:
+            # print('loading evaluator for task', cur_task)
+            model_path = os.path.join(
+                dataset_infos.base_path, "data/evaluator", f"{cur_task}.joblib"
+            )
+            os.makedirs(os.path.dirname(model_path), exist_ok=True)
+            evaluator = TaskModel(model_path, cur_task)
+            self.task_evaluator[cur_task] = evaluator
+
+    def forward(self, molecules, targets, name, current_epoch, val_counter, test=False):
+        if isinstance(targets, list):
+            targets_cat = torch.cat(targets, dim=0)
+            targets_np = targets_cat.detach().cpu().numpy()
+        else:
+            targets_np = targets.detach().cpu().numpy()
+
+        unique_smiles, all_smiles, all_metrics, targets_log = compute_molecular_metrics(
+            molecules,
+            targets_np,
+            self.train_smiles,
+            self.stat_ref,
+            self.dataset_infos,
+            self.task_evaluator,
+            self.comput_config,
+        )
+
+        if test:
+            file_name = "final_smiles.txt"
+            with open(file_name, "w") as fp:
+                all_tasks_name = list(self.task_evaluator.keys())
+                all_tasks_name = all_tasks_name.copy()
+                if 'meta_taskname' in all_tasks_name:
+                    all_tasks_name.remove('meta_taskname')
+                if 'scs' in all_tasks_name:
+                    all_tasks_name.remove('scs')
+
+                all_tasks_str = "smiles, " + ", ".join([f"input_{task}" for task in all_tasks_name] + [f"output_{task}" for task in all_tasks_name])
+                fp.write(all_tasks_str + "\n")
+                for i, smiles in enumerate(all_smiles):
+                    if targets_log is not None:
+                        all_result_str = f"{smiles}, " + ", ".join([f"{targets_log['input_'+task][i]}" for task in all_tasks_name] + [f"{targets_log['output_'+task][i]}" for task in all_tasks_name])
+                        fp.write(all_result_str + "\n")
+                    else:
+                        fp.write("%s\n" % smiles)
+                print("All smiles saved")
+        else:
+            result_path = os.path.join(os.getcwd(), f"graphs/{name}")
+            os.makedirs(result_path, exist_ok=True)
+            text_path = os.path.join(
+                result_path,
+                f"valid_unique_molecules_e{current_epoch}_b{val_counter}.txt",
+            )
+            textfile = open(text_path, "w")
+            for smiles in unique_smiles:
+                textfile.write(smiles + "\n")
+            textfile.close()
+
+        all_logs = all_metrics
+        if test:
+            all_logs["log_name"] = "test"
+        else:
+            all_logs["log_name"] = (
+                "epoch" + str(current_epoch) + "_batch" + str(val_counter)
+            )
+        
+        result_to_csv("output.csv", all_logs)
+        return all_smiles
+
+    def reset(self):
+        pass
+
+if __name__ == "__main__":
+    pass

mcd/metrics/molecular_metrics_train.py

@@ -0,0 +1,126 @@
+import torch
+from torchmetrics import Metric, MetricCollection
+from torch import Tensor
+import torch.nn as nn
+
+class CEPerClass(Metric):
+    full_state_update = False
+    def __init__(self, class_id):
+        super().__init__()
+        self.class_id = class_id
+        self.add_state('total_ce', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.softmax = torch.nn.Softmax(dim=-1)
+        self.binary_cross_entropy = torch.nn.BCELoss(reduction='sum')
+    
+    def update(self, preds: Tensor, target: Tensor) -> None:
+        """Update state with predictions and targets.
+        Args:
+            preds: Predictions from model   (bs, n, d) or (bs, n, n, d)
+            target: Ground truth values     (bs, n, d) or (bs, n, n, d)
+        """
+        target = target.reshape(-1, target.shape[-1])
+        mask = (target != 0.).any(dim=-1)
+
+        prob = self.softmax(preds)[..., self.class_id]
+        prob = prob.flatten()[mask]
+
+        target = target[:, self.class_id]
+        target = target[mask]
+
+        output = self.binary_cross_entropy(prob, target)
+
+        self.total_ce += output
+        self.total_samples += prob.numel()
+
+    def compute(self):
+        return self.total_ce / self.total_samples
+
+
+class AtomCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+class NoBondCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+
+class SingleCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+
+class DoubleCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+
+class TripleCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+
+class AromaticCE(CEPerClass):
+    def __init__(self, i):
+        super().__init__(i)
+
+
+class AtomMetricsCE(MetricCollection):
+    def __init__(self, active_atoms):
+        metrics_list = []
+        
+        for i, atom_type in enumerate(active_atoms):
+            metrics_list.append(type(f'{atom_type}_CE', (AtomCE,), {})(i))
+
+        super().__init__(metrics_list)
+
+
+class BondMetricsCE(MetricCollection):
+    def __init__(self):
+        ce_no_bond = NoBondCE(0)
+        ce_SI = SingleCE(1)
+        ce_DO = DoubleCE(2)
+        ce_TR = TripleCE(3)
+        super().__init__([ce_no_bond, ce_SI, ce_DO, ce_TR])
+
+
+class TrainMolecularMetricsDiscrete(nn.Module):
+    def __init__(self, dataset_infos):
+        super().__init__()
+        active_atoms = dataset_infos.active_atoms
+        self.train_atom_metrics = AtomMetricsCE(active_atoms=active_atoms)
+        self.train_bond_metrics = BondMetricsCE()
+
+    def forward(self, masked_pred_X, masked_pred_E, true_X, true_E, log: bool):
+        self.train_atom_metrics(masked_pred_X, true_X)
+        self.train_bond_metrics(masked_pred_E, true_E)
+        if log:
+            to_log = {}
+            for key, val in self.train_atom_metrics.compute().items():
+                to_log['train/' + key] = val.item()
+            for key, val in self.train_bond_metrics.compute().items():
+                to_log['train/' + key] = val.item()
+
+    def reset(self):
+        for metric in [self.train_atom_metrics, self.train_bond_metrics]:
+            metric.reset()
+
+    def log_epoch_metrics(self, current_epoch, log=True):
+        epoch_atom_metrics = self.train_atom_metrics.compute()
+        epoch_bond_metrics = self.train_bond_metrics.compute()
+
+        to_log = {}
+        for key, val in epoch_atom_metrics.items():
+            to_log['train_epoch/' + key] = val.item()
+        for key, val in epoch_bond_metrics.items():
+            to_log['train_epoch/' + key] = val.item()
+
+        for key, val in epoch_atom_metrics.items():
+            epoch_atom_metrics[key] = round(val.item(),4)
+        for key, val in epoch_bond_metrics.items():
+            epoch_bond_metrics[key] = round(val.item(),4)
+
+        if log:
+            print(f"Epoch {current_epoch}: {epoch_atom_metrics} -- {epoch_bond_metrics}")
+

mcd/metrics/property_metric.py

@@ -0,0 +1,201 @@
+import math, os
+import pickle
+import os.path as op
+
+import numpy as np
+import pandas as pd
+from joblib import dump, load
+from sklearn.ensemble import RandomForestClassifier, RandomForestRegressor
+from sklearn.metrics import mean_absolute_error, roc_auc_score
+
+
+from rdkit import Chem
+from rdkit import rdBase
+from rdkit.Chem import AllChem
+from rdkit import DataStructs
+from rdkit.Chem import rdMolDescriptors
+rdBase.DisableLog('rdApp.error')
+
+task_to_colname = {
+    'hiv_b': 'HIV_active',
+    'bace_b': 'Class',
+    'bbbp_b': 'p_np',
+    'O2': 'O2',
+    'N2': 'N2',
+    'CO2': 'CO2',
+}
+
+tasktype_name = {
+    'hiv_b': 'classification',
+    'bace_b': 'classification',
+    'bbbp_b': 'classification',
+    'O2': 'regression',
+    'N2': 'regression',
+    'CO2': 'regression',
+}
+
+class TaskModel():
+    """Scores based on an ECFP classifier."""
+    def __init__(self, model_path, task_name):
+        task_type = tasktype_name[task_name]
+        self.task_name = task_name
+        self.task_type = task_type
+        self.model_path = model_path
+        self.metric_func = roc_auc_score if 'classification' in self.task_type else mean_absolute_error
+
+        try:
+            self.model = load(model_path)
+            print(self.task_name, ' evaluator loaded')
+        except:
+            print(self.task_name, ' evaluator not found, training new one...')
+            if 'classification' in task_type:
+                self.model = RandomForestClassifier(random_state=0)
+            elif 'regression' in task_type:
+                self.model = RandomForestRegressor(random_state=0)
+            perfermance = self.train()
+            dump(self.model, model_path)
+            print('Oracle peformance: ', perfermance)
+
+    def train(self):
+        data_path = os.path.dirname(self.model_path)
+        data_path = os.path.join(os.path.dirname(self.model_path), '..', f'raw/{self.task_name}.csv.gz')
+        df = pd.read_csv(data_path)
+        col_name = task_to_colname[self.task_name]
+        y = df[col_name].to_numpy()
+        x_smiles = df['smiles'].to_numpy()
+        mask = ~np.isnan(y)
+        y = y[mask]
+
+        if 'classification' in self.task_type:
+            y = y.astype(int)
+
+        x_smiles = x_smiles[mask]
+        x_fps = []
+        mask = []
+        for i,smiles in enumerate(x_smiles):
+            mol = Chem.MolFromSmiles(smiles)
+            mask.append( int(mol is not None) )
+            fp = TaskModel.fingerprints_from_mol(mol) if mol else np.zeros((1, 2048))
+            x_fps.append(fp)
+        x_fps = np.concatenate(x_fps, axis=0)
+        self.model.fit(x_fps, y)
+        y_pred = self.model.predict(x_fps)
+        perf = self.metric_func(y, y_pred)
+        print(f'{self.task_name} performance: {perf}')
+        return perf
+
+    def __call__(self, smiles_list):
+        fps = []
+        mask = []
+        for i,smiles in enumerate(smiles_list):
+            mol = Chem.MolFromSmiles(smiles)
+            mask.append( int(mol is not None) )
+            fp = TaskModel.fingerprints_from_mol(mol) if mol else np.zeros((1, 2048))
+            fps.append(fp)
+
+        fps = np.concatenate(fps, axis=0)
+        if 'classification' in self.task_type:
+            scores = self.model.predict_proba(fps)[:, 1]
+        else:
+            scores = self.model.predict(fps)
+        scores = scores * np.array(mask)
+        return np.float32(scores)
+
+    @classmethod
+    def fingerprints_from_mol(cls, mol):  # use ECFP4
+        features_vec = AllChem.GetMorganFingerprintAsBitVect(mol, 2, nBits=2048)
+        features = np.zeros((1,))
+        DataStructs.ConvertToNumpyArray(features_vec, features)
+        return features.reshape(1, -1)
+
+###### SAS Score ######
+_fscores = None
+
+def readFragmentScores(name='fpscores'):
+    import gzip
+    global _fscores
+    # generate the full path filename:
+    if name == "fpscores":
+        name = op.join(op.dirname(__file__), name)
+    data = pickle.load(gzip.open('%s.pkl.gz' % name))
+    outDict = {}
+    for i in data:
+        for j in range(1, len(i)):
+            outDict[i[j]] = float(i[0])
+    _fscores = outDict
+
+def numBridgeheadsAndSpiro(mol, ri=None):
+    nSpiro = rdMolDescriptors.CalcNumSpiroAtoms(mol)
+    nBridgehead = rdMolDescriptors.CalcNumBridgeheadAtoms(mol)
+    return nBridgehead, nSpiro
+
+def calculateSAS(smiles_list):
+    scores = []
+    for i, smiles in enumerate(smiles_list):
+        mol = Chem.MolFromSmiles(smiles)
+        score = calculateScore(mol)
+        scores.append(score)
+    return np.float32(scores)
+
+def calculateScore(m):
+    if _fscores is None:
+        readFragmentScores()
+
+    # fragment score
+    fp = rdMolDescriptors.GetMorganFingerprint(m,
+                                               2)  # <- 2 is the *radius* of the circular fingerprint
+    fps = fp.GetNonzeroElements()
+    score1 = 0.
+    nf = 0
+    for bitId, v in fps.items():
+        nf += v
+        sfp = bitId
+        score1 += _fscores.get(sfp, -4) * v
+    score1 /= nf
+
+    # features score
+    nAtoms = m.GetNumAtoms()
+    nChiralCenters = len(Chem.FindMolChiralCenters(m, includeUnassigned=True))
+    ri = m.GetRingInfo()
+    nBridgeheads, nSpiro = numBridgeheadsAndSpiro(m, ri)
+    nMacrocycles = 0
+    for x in ri.AtomRings():
+        if len(x) > 8:
+            nMacrocycles += 1
+
+    sizePenalty = nAtoms**1.005 - nAtoms
+    stereoPenalty = math.log10(nChiralCenters + 1)
+    spiroPenalty = math.log10(nSpiro + 1)
+    bridgePenalty = math.log10(nBridgeheads + 1)
+    macrocyclePenalty = 0.
+    # ---------------------------------------
+    # This differs from the paper, which defines:
+    #  macrocyclePenalty = math.log10(nMacrocycles+1)
+    # This form generates better results when 2 or more macrocycles are present
+    if nMacrocycles > 0:
+        macrocyclePenalty = math.log10(2)
+
+    score2 = 0. - sizePenalty - stereoPenalty - spiroPenalty - bridgePenalty - macrocyclePenalty
+
+    # correction for the fingerprint density
+    # not in the original publication, added in version 1.1
+    # to make highly symmetrical molecules easier to synthetise
+    score3 = 0.
+    if nAtoms > len(fps):
+        score3 = math.log(float(nAtoms) / len(fps)) * .5
+
+    sascore = score1 + score2 + score3
+
+    # need to transform "raw" value into scale between 1 and 10
+    min = -4.0
+    max = 2.5
+    sascore = 11. - (sascore - min + 1) / (max - min) * 9.
+    # smooth the 10-end
+    if sascore > 8.:
+        sascore = 8. + math.log(sascore + 1. - 9.)
+    if sascore > 10.:
+        sascore = 10.0
+    elif sascore < 1.:
+        sascore = 1.0
+
+    return sascore

mcd/metrics/train_loss.py

@@ -0,0 +1,94 @@
+import time
+import torch
+import torch.nn as nn
+from metrics.abstract_metrics import CrossEntropyMetric
+from torchmetrics import Metric, MeanSquaredError
+
+# from 2:He to 119:*
+valencies_check = [0, 1, 2, 3, 4, 3, 2, 1, 0, 1, 2, 6, 6, 7, 6, 1, 0, 1, 2, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 3, 4, 7, 6, 1, 0, 1, 2, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 3, 4, 7, 6, 5, 6, 1, 2, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 3, 4, 7, 6, 5, 0, 1, 2, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1]
+valencies_check = torch.tensor(valencies_check)
+
+weight_check = [4.003, 6.941, 9.012, 10.812, 12.011, 14.007, 15.999, 18.998, 20.18, 22.99, 24.305, 26.982, 28.086, 30.974, 32.067, 35.453, 39.948, 39.098, 40.078, 44.956, 47.867, 50.942, 51.996, 54.938, 55.845, 58.933, 58.693, 63.546, 65.39, 69.723, 72.61, 74.922, 78.96, 79.904, 83.8, 85.468, 87.62, 88.906, 91.224, 92.906, 95.94, 98.0, 101.07, 102.906, 106.42, 107.868, 112.412, 114.818, 118.711, 121.76, 127.6, 126.904, 131.29, 132.905, 137.328, 138.906, 140.116, 140.908, 144.24, 145.0, 150.36, 151.964, 157.25, 158.925, 162.5, 164.93, 167.26, 168.934, 173.04, 174.967, 178.49, 180.948, 183.84, 186.207, 190.23, 192.217, 195.078, 196.967, 200.59, 204.383, 207.2, 208.98, 209.0, 210.0, 222.0, 223.0, 226.0, 227.0, 232.038, 231.036, 238.029, 237.0, 244.0, 243.0, 247.0, 247.0, 251.0, 252.0, 257.0, 258.0, 259.0, 262.0, 267.0, 268.0, 269.0, 270.0, 269.0, 278.0, 281.0, 281.0, 285.0, 284.0, 289.0, 288.0, 293.0, 292.0, 294.0, 294.0]
+weight_check = torch.tensor(weight_check)
+
+class AtomWeightMetric(Metric):
+    def __init__(self):
+        super().__init__()
+        self.add_state('total_loss', default=torch.tensor(0.), dist_reduce_fx="sum")
+        self.add_state('total_samples', default=torch.tensor(0.), dist_reduce_fx="sum")
+        global weight_check
+        self.weight_check = weight_check
+
+    def update(self, X, Y):
+        atom_pred_num = X.argmax(dim=-1)
+        atom_real_num = Y.argmax(dim=-1)
+        self.weight_check = self.weight_check.type_as(X)
+
+        pred_weight = self.weight_check[atom_pred_num]
+        real_weight = self.weight_check[atom_real_num]
+
+        lss = 0
+        lss += torch.abs(pred_weight.sum(dim=-1) - real_weight.sum(dim=-1)).sum()
+        self.total_loss += lss
+        self.total_samples += X.size(0)
+
+    def compute(self):
+        return self.total_loss / self.total_samples
+
+
+class TrainLossDiscrete(nn.Module):
+    """ Train with Cross entropy"""
+    def __init__(self, lambda_train, weight_node=None, weight_edge=None):
+        super().__init__()
+        self.node_loss = CrossEntropyMetric()
+        self.edge_loss = CrossEntropyMetric()
+        self.weight_loss = AtomWeightMetric()
+
+        self.y_loss = MeanSquaredError()
+        self.lambda_train = lambda_train
+
+    def forward(self, masked_pred_X, masked_pred_E, pred_y, true_X, true_E, true_y, node_mask, log: bool):
+        """ Compute train metrics
+        masked_pred_X : tensor -- (bs, n, dx)
+        masked_pred_E : tensor -- (bs, n, n, de)
+        pred_y : tensor -- (bs, )
+        true_X : tensor -- (bs, n, dx)
+        true_E : tensor -- (bs, n, n, de)
+        true_y : tensor -- (bs, )
+        log : boolean. """
+
+        loss_weight = self.weight_loss(masked_pred_X, true_X)
+        
+        true_X = torch.reshape(true_X, (-1, true_X.size(-1)))  # (bs * n, dx)
+        true_E = torch.reshape(true_E, (-1, true_E.size(-1)))  # (bs * n * n, de)
+        masked_pred_X = torch.reshape(masked_pred_X, (-1, masked_pred_X.size(-1)))  # (bs * n, dx)
+        masked_pred_E = torch.reshape(masked_pred_E, (-1, masked_pred_E.size(-1)))   # (bs * n * n, de)
+
+        # Remove masked rows
+        mask_X = (true_X != 0.).any(dim=-1)
+        mask_E = (true_E != 0.).any(dim=-1)
+
+        flat_true_X = true_X[mask_X, :]
+        flat_pred_X = masked_pred_X[mask_X, :]
+
+        flat_true_E = true_E[mask_E, :]
+        flat_pred_E = masked_pred_E[mask_E, :]
+        
+        loss_X = self.node_loss(flat_pred_X, flat_true_X) if true_X.numel() > 0 else 0.0
+        loss_E = self.edge_loss(flat_pred_E, flat_true_E) if true_E.numel() > 0 else 0.0
+
+        return self.lambda_train[0] * loss_X + self.lambda_train[1] * loss_E + loss_weight
+
+    def reset(self):
+        for metric in [self.node_loss, self.edge_loss, self.y_loss]:
+            metric.reset()
+
+    def log_epoch_metrics(self, current_epoch, start_epoch_time, log=True):
+        epoch_node_loss = self.node_loss.compute() if self.node_loss.total_samples > 0 else -1
+        epoch_edge_loss = self.edge_loss.compute() if self.edge_loss.total_samples > 0 else -1
+        epoch_weight_loss = self.weight_loss.compute() if self.weight_loss.total_samples > 0 else -1
+
+        if log:
+            print(f"Epoch {current_epoch} finished: X_CE: {epoch_node_loss :.4f} -- E_CE: {epoch_edge_loss :.4f} "
+                f"Weight: {epoch_weight_loss :.4f} "
+                f"-- Time taken {time.time() - start_epoch_time:.1f}s ")