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Introduction to dynamical systems analysis in quantitative systems pharmacology: basic concepts and applications

Authors
 Dongwoo Chae 
Citation
 Translational and Clinical Pharmacology, Vol.28(3) : 109-125, 2020-09 
Journal Title
Translational and Clinical Pharmacology
ISSN
 2289-0882 
Issue Date
2020-09
Keywords
Bifurcation ; Dynamical Systems Theory ; Multistability ; Quantitative Systems Pharmacology ; Systems Biology
Abstract
Quantitative systems pharmacology (QSP) can be regarded as a hybrid of pharmacometrics and systems biology. Here, we introduce the basic concepts related to dynamical systems theory that are fundamental to the analysis of systems biology models. Determination of the fixed points and their local stabilities constitute the most important step. Illustration of a phase portrait further helps investigate multistability and bifurcation behavior. As a motivating example, we examine a cell circuit model that deals with tissue inflammation and fibrosis. We show how increasing the severity and duration of inflammatory stimuli divert the system trajectories towards pathological fibrosis. Simulations that involve different parameter values offer important insights into the potential bifurcations and the development of efficient therapeutic strategies. We expect that this tutorial serves as a good starting point for pharmacometricians striving to widen their scope to QSP and physiologically-oriented modeling.
Files in This Item:
T202004915.pdf Download
DOI
10.12793/tcp.2020.28.e12
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Chae, Dong Woo(채동우) ORCID logo https://orcid.org/0000-0002-7675-3821
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180563
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