NDLI: Kinetic perturbations as robustness analysis tool for biochemical reaction networks

Content Provider	IEEE Xplore Digital Library
Author	Waldherr, S. Allgower, F. Jacobsen, E.W.
Copyright Year	2009
Description	Author affiliation: S3-Automatic Control, Royal Institute of Technology - KTH, S-100 44 Stockholm, Sweden (Jacobsen, E.W.) \|\| Institute for Systems Theory and Automatic Control, Universität Stuttgart, 70550, Germany (Waldherr, S.; Allgower, F.)
Abstract	Models of biochemical reaction networks can be decomposed into a stoichiometric part and a kinetic part. The stoichiometric part describes the structural mass flows while the kinetic part describes how the flow rates vary with substrate concentrations and regulatory interactions. Herein a method for analyzing the robustness of biochemical networks with respect to perturbations of the kinetic part is proposed. In particular, we consider a class of perturbations that modify the local kinetic slopes while leaving the reaction flow rates in steady state unchanged. A method for computing the associated robustness radii for perturbations of single or multiple kinetic slopes is devised. The corresponding non-robust perturbations can be implemented in the original nonlinear model through specific parameter variations described by the perturbation class. The proposed method is illustrated through application to the Huang-Ferrell model of MAPK signaling cascades. In particular, we compute the smallest kinetic perturbations that translate the nominal utltrasensitive response into a bistable and oscillatory response, respectively. The results are highly relevant since MAPK cascades are conserved pathways known to produce bistability as well as sustained oscillations depending on the context in which they operate.
Starting Page	4572
Ending Page	4577
File Size	619369
Page Count	6
File Format	PDF
ISBN	9781424438716
ISSN	01912216
DOI	10.1109/CDC.2009.5400939
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2009-12-15
Publisher Place	China
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Kinetic theory Robustness Biochemical analysis Steady-state Jacobian matrices Robust control Signal analysis Biological system modeling Differential equations Systems biology
Content Type	Text
Resource Type	Article

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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