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定量生物学方法——从单细胞显微镜图像分析到随机基因表达预测模型的推断

Methods in quantitative biology-from analysis of single-cell microscopy images to inference of predictive models for stochastic gene expression.

作者信息

Aguilera Luis U, Weber Lisa M, Ron Eric, King Connor R, Öcal Kaan, Popinga Alex, Cook Joshua, May Michael P, Raymond William S, Fox Zachary R, Forero-Quintero Linda S, Forman Jack R, David Alexandre, Munsky Brian

机构信息

Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, United States of America.

Department of Biochemistry and Molecular Genetics, University of Colorado-Anschutz Medical Campus, Aurora, CO 80045, United States of America.

出版信息

Phys Biol. 2025 Jun 10;22(4):042001. doi: 10.1088/1478-3975/adda85.

Abstract

The field of quantitative biology (q-bio) seeks to provide precise and testable explanations for observed biological phenomena by applying mathematical and computational methods. The central goals of q-bio are to (1) systematically propose quantitative hypotheses in the form of mathematical models, (2) demonstrate that these models faithfully capture a specific essence of a biological process, and (3) correctly forecast the dynamics of the process in new, and previously untested circumstances. Achieving these goals depends on accurate analysis and incorporating informative experimental data to constrain the set of potential mathematical representations. In this introductory tutorial, we provide an overview of the state of the field and introduce some of the computational methods most commonly used in q-bio. In particular, we examine experimental techniques in single-cell imaging, computational tools to process images and extract quantitative data, various mechanistic modeling approaches used to reproduce these quantitative data, and techniques for data-driven model inference and model-driven experiment design. All topics are presented in the context of additional online resources, including open-source Python notebooks and open-ended practice problems that comprise the technical content of the annual Undergraduate Quantitative Biology Summer School (UQ-Bio).

摘要

定量生物学(q-bio)领域试图通过应用数学和计算方法,为观察到的生物学现象提供精确且可检验的解释。q-bio的核心目标是:(1)以数学模型的形式系统地提出定量假设;(2)证明这些模型忠实地捕捉了生物过程的特定本质;(3)在新的、以前未测试过的情况下正确预测该过程的动态变化。实现这些目标依赖于准确的分析,并纳入信息丰富的实验数据以限制潜在数学表示的集合。在本入门教程中,我们概述了该领域的现状,并介绍了q-bio中一些最常用的计算方法。特别是,我们研究了单细胞成像中的实验技术、处理图像和提取定量数据的计算工具、用于重现这些定量数据的各种机理建模方法,以及数据驱动的模型推断和模型驱动的实验设计技术。所有主题都结合了额外的在线资源进行介绍,包括开源Python笔记本和开放式实践问题,这些构成了年度本科定量生物学暑期学校(UQ-Bio)的技术内容。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c7/12150428/620219831f9e/pbadda85f1_hr.jpg

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