Agentic Discovery Transfer Enables Cross-Cancer Discovery at Scale

Cancer research generates tens of thousands of studies each year, yet whether a published finding holds in another cancer type or patient population is rarely tested, because doing so is labor-intensive and difficult to scale. We define this task as discovery transfer and present SMART, a multi-agent large language model framework for discovery transfer in single-cell RNA-sequencing (scRNA-seq) studies. Given a source manuscript and a target scRNA-seq dataset, SMART extracts major clinical and mechanistic findings, generates and executes analyses for the testable findings, and reports which findings transfer and suggests follow-up. Applied to 121 studies across six cancer types, SMART identified findings that transfer across cancers, including a lung cancer prognostic signature that we confirmed to be associated with survival in liver cancer, pancreatic cancer and pleural mesothelioma. SMART also generated new mechanistic hypotheses, demonstrating how agentic discovery transfer can extend published findings beyond their original setting.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-29
DOI
https://doi.org/10.64898/2026.10.28.762506
Primary Topic
Single-cell and spatial transcriptomics
Type
preprint

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preprint

Agentic Discovery Transfer Enables Cross-Cancer Discovery at Scale

P. Khatri, Jack M. Shireman, Mahua Dey, Christina M. Kendziorski et al.
3 links
bioRxiv (Cold Spring Harbor Laboratory)
Single-cell and spatial transcriptomics
preprint

Agentic Discovery Transfer Enables Cross-Cancer Discovery at Scale

P. Khatri, Jack M. Shireman, Mahua Dey, Christina M. Kendziorski, Yujia Cai, Lingxin Cheng, Yixuan Xie, Akash GOGATE, Maggie Stangis
preprint en

Abstract

Cancer research generates tens of thousands of studies each year, yet whether a published finding holds in another cancer type or patient population is rarely tested, because doing so is labor-intensive and difficult to scale. We define this task as discovery transfer and present SMART, a multi-agent large language model framework for discovery transfer in single-cell RNA-sequencing (scRNA-seq) studies. Given a source manuscript and a target scRNA-seq dataset, SMART extracts major clinical and mechanistic findings, generates and executes analyses for the testable findings, and reports which findings transfer and suggests follow-up. Applied to 121 studies across six cancer types, SMART identified findings that transfer across cancers, including a lung cancer prognostic signature that we confirmed to be associated with survival in liver cancer, pancreatic cancer and pleural mesothelioma. SMART also generated new mechanistic hypotheses, demonstrating how agentic discovery transfer can extend published findings beyond their original setting.

bioRxiv (Cold Spring Harbor Laboratory)
University of Wisconsin System (US), University of Wisconsin–Madison (US)
National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Good health and well-being
Single-cell and spatial transcriptomics
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