{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:52:53Z","timestamp":1790427173987,"version":"4.1.0"},"posted":{"date-parts":[[2026,8,14]]},"group-title":"Bioinformatics","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health","award":["U24-HL148865"],"award-info":[{"award-number":["U24-HL148865"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/chat.lungmap.net\">https:\/\/chat.lungmap.net<\/jats:ext-link>\n                  ), 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 (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04598919\">NCT04598919<\/jats:ext-link>\n                  ). 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.\n                <\/jats:p>","DOI":"10.64898\/2026.08.08.743577","type":"posted-content","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:10:10Z","timestamp":1786731010000},"source":"Crossref","is-referenced-by-count":1,"title":["A Conversational Multi-Agent AI System for Integrated Multi-Omics Analysis and Biomedical Discovery"],"prefix":"10.64898","author":[{"given":"Pankaj","family":"Rajdeo","sequence":"first","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Biomedical Informatics, University of Cincinnati, OH, 45267 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunya","family":"Asanuma","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Biomedical Informatics, University of Cincinnati, OH, 45267 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kouril","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Biomedical Informatics, University of Cincinnati, OH, 45267 USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, OH, 45267 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, OH, 45267 USA"},{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, 45229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Chadha","sequence":"additional","affiliation":[{"name":"Apple Corporation, Cupertino, CA 95014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-7453","authenticated-orcid":false,"given":"V. 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