Predicting and generating antibiotics against future pathogens with ApexOracle

TL;DR

ApexOracle is an AI system that predicts antibiotic activity and designs new molecules against emerging pathogens, integrating pathogen-specific data for rapid and effective antimicrobial discovery.

Contribution

It introduces a novel AI model combining molecular features and pathogen context to predict and generate antibiotics for previously unseen strains.

Findings

Outperforms existing methods in activity prediction across diverse bacteria.

Demonstrates reliable transferability to novel pathogens with limited data.

Enables in silico design of new molecules with high predicted efficacy.

Abstract

Antimicrobial resistance (AMR) is escalating and outpacing current antibiotic development. Thus, discovering antibiotics effective against emerging pathogens is becoming increasingly critical. However, existing approaches cannot rapidly identify effective molecules against novel pathogens or emerging drug-resistant strains. Here, we introduce ApexOracle, an artificial intelligence (AI) model that both predicts the antibacterial potency of existing compounds and designs de novo molecules active against strains it has never encountered. Departing from models that rely solely on molecular features, ApexOracle incorporates pathogen-specific context through the integration of molecular features captured via a foundational discrete diffusion language model and a dual-embedding framework that combines genomic- and literature-derived strain representations. Across diverse bacterial species and chemical modalities, ApexOracle consistently outperformed state-of-the-art approaches in activity prediction and demonstrated reliable transferability to novel pathogens with little or no antimicrobial data. Its unified representation-generation architecture further enables the in silico creation of "new-to-nature" molecules with high predicted efficacy against priority threats. By pairing rapid activity prediction with targeted molecular generation, ApexOracle offers a scalable strategy for countering AMR and preparing for future infectious-disease outbreaks.