气候变化领域集成服务门户(CCPortal): The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling

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DOI	10.1073/PNAS.2022598118
	The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling
	Gates A.J.; Correia R.B.; Wang X.; Rocha L.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	The ability to map causal interactions underlying genetic control and cellular signaling has led to increasingly accurate models of the complex biochemical networks that regulate cellular function. These network models provide deep insights into the organization, dynamics, and function of biochemical systems: For example, by revealing genetic control pathways involved in disease. However, the traditional representation of biochemical networks as binary interaction graphs fails to accurately represent an important dynamical feature of these multivariate systems: Some pathways propagate control signals much more effectively than do others. Such heterogeneity of interactions reflects canalization-the system is robust to dynamical interventions in redundant pathways but responsive to interventions in effective pathways. Here, we introduce the effective graph, a weighted graph that captures the nonlinear logical redundancy present in biochemical network regulation, signaling, and control. Using 78 experimentally validated models derived from systems biology, we demonstrate that 1) redundant pathways are prevalent in biological models of biochemical regulation, 2) the effective graph provides a probabilistic but precise characterization of multivariate dynamics in a causal graph form, and 3) the effective graph provides an accurate explanation of how dynamical perturbation and control signals, such as those induced by cancer drug therapies, propagate in biochemical pathways. Overall, our results indicate that the effective graph provides an enriched description of the structure and dynamics of networked multivariate causal interactions. We demonstrate that it improves explainability, prediction, and control of complex dynamical systems in general and biochemical regulation in particular. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biochemical regulation; Boolean network; Canalization; Complex networks; Complex networks
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180206
作者单位	Network Science Institute, Northeastern University, Boston, MA 02115, United States; Instituto Gulbenkian de Ciencia, Oeiras, 2780-156, Portugal; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Ministry of Education of Brazil, Brasilia, DF, 70040-020, Brazil; Center for Social and Biomedical Complexity, Luddy School of Informatics, Computing and Engineering, Indiana University, Bloomington, IN 47408, United States; Department of Systems Science and Industrial Engineering, Binghamton University, Binghamton, NY 13902, United States
推荐引用方式 GB/T 7714	Gates A.J.,Correia R.B.,Wang X.,et al. The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling[J],2021,118(12).
APA	Gates A.J.,Correia R.B.,Wang X.,&Rocha L.M..(2021).The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Gates A.J.,et al."The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).