Digitize your Biology! Modeling multicellular systems through interpretable cell behavior
Digitize your Biology! Modeling multicellular systems through interpretable cell behavior
Cells are fundamental units of life, constantly interacting and evolving as dynamical systems. While recent spatial multi-omics can quantitate individual cells' characteristics and regulatory programs, forecasting their evolution ultimately requires mathematical modeling. We develop a conceptual framework--a cell behavior hypothesis grammar--that uses natural language statements (cell rules) to create mathematical models. This allows us to systematically integrate biological knowledge and multi-omics data to make them computable. We can then perform virtual "thought experiments" that challenge and extend our understanding of multicellular systems, and ultimately generate new testable hypotheses. In this paper, we motivate and describe the grammar, provide a reference implementation, and demonstrate its potential through a series of examples in tumor biology and immunotherapy. Altogether, this approach provides a bridge between biological, clinical, and systems biology researchers for mathematical modeling of biological systems at scale, allowing the community to extrapolate from single-cell characterization to emergent multicellular behavior.
Godet Ines、Wirtz Denis、Johnson Jeanette A.I.、Kurtoglu Furkan、Metzcar John、Raddatz Andrew、Solorzano Jacobo、Wang Yafei、Kagohara Luciane T.、Kiemen Ashley L.、Zaidi Neeha、Zheng Lei、Chang Young Hwan、Coussens Lisa、Fertig Elana J.、Macklin Paul、Bergman Daniel、Forjaz Andre、Heiser Laura M.、Thompson Elizabeth D.、Deshpande Atul、Rocha Heber L.、Jaffee Elizabeth M.、Getz Michael、Sundus Aneequa、Gray Joe、Wu Pei-Hsun、Gilkes Daniele M.、Zimmerman Jacquelyn W.、Lyman Melissa、Stein-O'Brien Genevieve L、Heiland Randy、Mitchell Jacob、Bucher Elmar、Booth Max
生物科学现状、生物科学发展生物科学研究方法、生物科学研究技术生物工程学
Godet Ines,Wirtz Denis,Johnson Jeanette A.I.,Kurtoglu Furkan,Metzcar John,Raddatz Andrew,Solorzano Jacobo,Wang Yafei,Kagohara Luciane T.,Kiemen Ashley L.,Zaidi Neeha,Zheng Lei,Chang Young Hwan,Coussens Lisa,Fertig Elana J.,Macklin Paul,Bergman Daniel,Forjaz Andre,Heiser Laura M.,Thompson Elizabeth D.,Deshpande Atul,Rocha Heber L.,Jaffee Elizabeth M.,Getz Michael,Sundus Aneequa,Gray Joe,Wu Pei-Hsun,Gilkes Daniele M.,Zimmerman Jacquelyn W.,Lyman Melissa,Stein-O'Brien Genevieve L,Heiland Randy,Mitchell Jacob,Bucher Elmar,Booth Max.Digitize your Biology! Modeling multicellular systems through interpretable cell behavior[EB/OL].(2025-03-28)[2025-06-23].https://www.biorxiv.org/content/10.1101/2023.09.17.557982.点此复制
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