GEM-GPT Enables Personalized Cell Type-Resolved Therapeutic Design for Systems Pharmacology
Year: 2026
Type: preprint
Abstract: Generative AI is transforming drug discovery, yet most approaches follow one-drug-one-target paradigms ill-suited to the heterogeneity of chronic, systemic diseases. Systems pharmacology offers an alternative, but generative tools designed for it remain scarce. We introduce GEM-GPT, a transcriptomics-guided framework that generates personalized therapeutic candidate molecules intended to shift cell type-specific disease states toward healthy phenotypes. GEM-GPT uses a biology-inspired deep fusion architecture that couples a single-cell RNA-sequencing foundation model with a molecular GPT, modeling cell type-specific chemical-gene interactions throughout molecule generation rather than through fixed conditioning. Across bulk and single-cell chemical perturbations and CRISPR knock-out signatures, GEM-GPT outperforms state-of-the-art baselines, produces cell type-resolved molecules, and generalizes to unseen cellular contexts. In a case study on opioid use disorder (OUD), it generates novel candidates, recovers FDA-approved OUD-related drugs absent from training, and yields predicted binders to OUD-related targets. GEM-GPT bridges single-cell omics and molecular generation for personalized, cell-type-resolved, systems-aware therapeutic design.
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: green
Awards: AI-powered cross-level cross-species omics data integration to elucidate mechanisms of EL, AI-Powered chemical-pathway-patient-directed polypharmacology for OUD therapy, AI-powered cross-level cross-species omics data integration to elucidate mechanisms of EL, AI-Powered Quantitative Systems Pharmacology for AD Drug Repurposing, AI-powered chemical proteomics for drug discovery targeting orphan proteins
OpenAlex ID: W7170039660