MolE

MolE - Antimicrobial Prediction

Short description

MolE learns task-independent molecular representations of chemicals via Graph Isomorphism Networks (GINs). Combined with an XGBoost classifier it estimates the probability of a compound inhibiting bacterial growth. The model was developed by Roberto Olayo Alarcon et al. and more information can be found in the GitHub repository and the accompanying paper.

Model versions

MolE Antimicrobial Prediction (March 2024): Pretrained representation model + XGBoost classifier trained on antimicrobial screening data (Maier et al., 2018).

Long description

MolE is a non-contrastive self-supervised Graph Neural Network (GNN) framework that leverages unlabeled chemical structures to learn task-independent molecular representations. By combining a pre-trained MolE representation with experimentally validated compound-bacteria activity data, the project builds an antimicrobial prediction model that re-discovers recently reported growth-inhibitory compounds that are structurally distinct from current antibiotics. Using the model as a compound prioritization strategy, three human-targeted drugs are identified and experimentally confirm as growth-inhibitors of Staphylococcus aureus, highlighting MolE’s potential to accelerate the discovery of new antibiotics.

<!-- MolE integrates molecular graph-based representation learning with gradient-boosted decision trees for predicting antimicrobial potential. The approach involves: 1. **Representation learning:** A graph neural network (GINet) trained on 100,000 randomly sampled compounds to derive molecular embeddings from SMILES strings. 2. **Prediction:** These embeddings are used as input to an **XGBoost** model that predicts antimicrobial activity scores across 40 bacterial strains, based on data from *Maier et al., 2018*. The model was developed by **Roberto Olayo Alarcon et al.**. Further information is available in the [paper](https://www.nature.com/articles/s41467-025-58804-4). -->

Metadata

Input

• Description: Table of chemicals with their SMILES representations.
• Input format:
  • Shape: [n, 2], where n is the number of chemical compounds
  • Columns:
    • chem_name (str): Name of the molecule (e.g., Halicin).
    • smiles (str): SMILES representation of the molecule (e.g.,C1=C(SC(=N1)SC2=NN=C(S2)N)[N+](=O)[O-]).
• Example input file: input/examples_molecules.tsv

Model

• Modality: String representations of chemical compounds in SMILES format
• Scale: Per bacterial strain and chemical compound.
• Description:
  • The model computes antimicrobial predictive probabilities for 40 bacterial strains contained in Maier et al., 2018, using a two-step process:
    1. Generate molecular embeddings with a pre-trained GINet representation model (model.pth, config.yaml).
    2. Predict antimicrobial properties with a trained XGBoost classifier (MolE-XGBoost-08.03.2024_14.20.pkl). The scores reflect the likelihood that a compound inhibits the growth of a given bacterial strain.
• Training data: 100000 randomly sampled compounds from ChemBERTa for the pretraining of MolE and data from Maier et al., 2018 containing the influence of 1197 marketed drugs on the growth of 40 bacterial strains for the XGBoost classifier
• Publication: Nature Communications (2025)

Output

• Description: For each compound, the model predicts growth inhibition scores for 40 different bacterial strains.
• Output format: table
  • Shape: [n × 40, 2], where n is the number of chemical compounds
  • Columns:
    • pred_id (str): Combination of the molecule name and bacterial strain (e.g., Halicin:Akkermansia muciniphila (NT5021)).
    • antimicrobial_predictive_probability (float): Predicted probability that the compound inhibits microbial growth.
• Example output file: output/example_molecules_prediction.tsv

Installation

Install the conda environment with all dependencies:

# Create the conda environment called virtual-human-chc-mole
conda env create -f environment.yaml

# Activate the environment
conda activate virtual-human-chc-mole

Example

Minimal inference example

import torch
import yaml
import pickle
import pandas as pd
from huggingface_hub import hf_hub_download
from mole_package import ginet_concat, mole_antimicrobial_prediction, mole_representation, dataset_representation

class MolE:
    def __init__(self, device='auto'):
        repo = "virtual-human-chc/MolE"
        self.device = "cuda:0" if device == "auto" and torch.cuda.is_available() else "cpu"

        # Download + load
        cfg = yaml.safe_load(open(hf_hub_download(repo, "config.yaml")))
        self.model = ginet_concat.GINet(**cfg["model"]).to(self.device)
        self.model.load_state_dict(torch.load(hf_hub_download(repo, "model.pth"), map_location=self.device))
        self.xgb = pickle.load(open(hf_hub_download(repo, "MolE-XGBoost-08.03.2024_14.20.pkl"), "rb"))

    def predict_from_smiles(self, smiles_tsv):
        smiles_df = mole_representation.read_smiles(smiles_tsv, "smiles", "chem_name")
        emb = dataset_representation.batch_representation(smiles_df, self.model, "smiles", "chem_name", device=self.device)
        X_input = mole_antimicrobial_prediction.add_strains(
            emb, "input/maier_screening_results.tsv.gz"
        )
        probs = self.xgb.predict_proba(X_input)[:, 1]
        return pd.DataFrame(
            {"antimicrobial_predictive_probability": probs},
            index=X_input.index
        )
        
# Run inference
mole = MolE()
pred = mole.predict_from_smiles("input/examples_molecules.tsv")
print(pred)

References

1. Roberto Olayo Alarcon et al., MolE: Graph-based molecular representation learning for antimicrobial discovery, Nature Communications (2025).
2. Maier et al., Extensive antimicrobial screening of small molecules, Nature (2018), https://www.nature.com/articles/nature25979.
3. GitHub repository: https://github.com/rolayoalarcon/MolE.
4. GitHub repository: https://github.com/rolayoalarcon/mole_antimicrobial_potential.
5. Model weights (Zenodo DOI): https://doi.org/10.5281/zenodo.10803099.

Copyright

Code derived from https://github.com/rolayoalarcon/MolE is licensed under the MIT License, © 2024 Roberto Olayo Alarcon. Model weights are licensed under Creative Commons Attribution 4.0 International (CC BY 4.0), © 2024 Roberto Olayo Alarcon. Additional code © 2025 Maksim Pavlov, licensed under MIT.