A Conversational Multi-Agent AI System for Integrated Multi-Omics Analysis and Biomedical Discovery

<jats:p> Single-cell and spatial omics offer unprecedented opportunities to decipher the mechanisms of disease, however, this process requires teams of experts, iterative trial-and-error and reasoning across modalities. Here we present LungChat (https://chat.lungmap.net), a conversational system for integrated multi-omics analysis and biomedical discovery, deployed as a hierarchical multi-agent architecture in which a supervisor decomposes natural-language questions into parallel, tool-grounded tasks spanning single-cell and spatial analyses, literature and clinical-trial synthesis, and drug repurposing. To predict new therapeutics, LungChat implements Direction-Aware Repurposing and Targeting (DART) to distinguish perturbations that reverse disease transcriptional programs from those that reinforce them, at the cell-type level, for safety prediction. Controlled architecture ablations showed that hierarchical orchestration improved grounded abstention and token efficiency and preserved strong performance on complex multi-step tasks. In pulmonary disease case studies, LungChat independently prioritized saracatinib for IPF through drug-connectivity screening, followed by DART-based cell-type analysis; the same compound has been evaluated in the STOP-IPF clinical trial ( <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04598919">NCT04598919</jats:ext-link> ). The system also recovered fluticasone propionate, an established COPD therapy, through a single orchestrated analysis. This tissue-agnostic system provides a blueprint for verifiable agentic AI systems that support reproducible scientific discovery. </jats:p>