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将你的生物学数字化!通过可解释的细胞行为对多细胞系统进行建模。

Digitize your Biology! Modeling multicellular systems through interpretable cell behavior.

作者信息

Johnson Jeanette A I, Stein-O'Brien Genevieve L, Booth Max, Heiland Randy, Kurtoglu Furkan, Bergman Daniel R, Bucher Elmar, Deshpande Atul, Forjaz André, Getz Michael, Godet Ines, Lyman Melissa, Metzcar John, Mitchell Jacob, Raddatz Andrew, Rocha Heber, Solorzano Jacobo, Sundus Aneequa, Wang Yafei, Gilkes Danielle, Kagohara Luciane T, Kiemen Ashley L, Thompson Elizabeth D, Wirtz Denis, Wu Pei-Hsun, Zaidi Neeha, Zheng Lei, Zimmerman Jacquelyn W, Jaffee Elizabeth M, Hwan Chang Young, Coussens Lisa M, Gray Joe W, Heiser Laura M, Fertig Elana J, Macklin Paul

机构信息

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. Baltimore, MD USA.

Convergence Institute, Johns Hopkins University. Baltimore, MD USA.

出版信息

bioRxiv. 2023 Nov 5:2023.09.17.557982. doi: 10.1101/2023.09.17.557982.

Abstract

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.

摘要

细胞是生命的基本单位,作为动态系统不断相互作用和进化。虽然最近的空间多组学技术可以量化单个细胞的特征和调控程序,但预测它们的进化最终需要数学建模。我们开发了一个概念框架——细胞行为假设语法,它使用自然语言陈述(细胞规则)来创建数学模型。这使我们能够系统地整合生物学知识和多组学数据,使其具有可计算性。然后,我们可以进行虚拟的“思想实验”,挑战并扩展我们对多细胞系统的理解,并最终产生新的可检验假设。在本文中,我们阐述并描述了该语法,提供了一个参考实现,并通过肿瘤生物学和免疫治疗中的一系列例子展示了其潜力。总之,这种方法为生物学、临床和系统生物学研究人员之间搭建了一座桥梁,以便对大规模生物系统进行数学建模,使该领域能够从单细胞特征推断出多细胞行为的出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c38/10627318/199d04798b77/nihpp-2023.09.17.557982v3-f0001.jpg

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