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基于数据驱动的细胞表型转变的控制方程重构:数据科学与系统生物学的整合。

Reconstructing data-driven governing equations for cell phenotypic transitions: integration of data science and systems biology.

机构信息

Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15232, United States of America.

Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15232, United States of America.

出版信息

Phys Biol. 2022 Sep 9;19(6). doi: 10.1088/1478-3975/ac8c16.

Abstract

Cells with the same genome can exist in different phenotypes and can change between distinct phenotypes when subject to specific stimuli and microenvironments. Some examples include cell differentiation during development, reprogramming for induced pluripotent stem cells and transdifferentiation, cancer metastasis and fibrosis progression. The regulation and dynamics of cell phenotypic conversion is a fundamental problem in biology, and has a long history of being studied within the formalism of dynamical systems. A main challenge for mechanism-driven modeling studies is acquiring sufficient amount of quantitative information for constraining model parameters. Advances in quantitative experimental approaches, especially high throughput single-cell techniques, have accelerated the emergence of a new direction for reconstructing the governing dynamical equations of a cellular system from quantitative single-cell data, beyond the dominant statistical approaches. Here I review a selected number of recent studies using live- and fixed-cell data and provide my perspective on future development.

摘要

具有相同基因组的细胞可以存在于不同的表型中,并且在受到特定刺激和微环境的影响时,可以在不同的表型之间转换。一些例子包括发育过程中的细胞分化、诱导多能干细胞的重编程和转分化、癌症转移和纤维化进展。细胞表型转换的调控和动力学是生物学中的一个基本问题,长期以来一直是在动力系统的形式主义中进行研究的。对于基于机制的建模研究的一个主要挑战是获取足够数量的定量信息来约束模型参数。定量实验方法的进步,特别是高通量单细胞技术的进步,加速了从定量单细胞数据中重建细胞系统的控制动力学方程的新方向的出现,超越了占主导地位的统计方法。在这里,我回顾了一些最近使用活细胞和固定细胞数据的研究,并就未来的发展提出了我的看法。

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