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Constructing kinetic models of metabolism at genome‐scales: A review

Constructing kinetic models of metabolism at genome‐scales: A review Constraint‐based modeling of biological networks (metabolism, transcription and signal transduction), although used successfully in many applications, suffer from specific limitations such as the lack of representation of metabolite concentrations and enzymatic regulation, which are necessary for a complete physiologically relevant model. Kinetic models conversely overcome these shortcomings and enable dynamic analysis of biological systems for enhanced in silico hypothesis generation. Nonetheless, kinetic models also have limitations for modeling at genome‐scales chiefly due to: (i) model non‐linearity; (ii) computational tractability; (iii) parameter identifiability; (iv) estimability; and (v) uncertainty. In order to support further development of kinetic models as viable alternatives to constraint‐based models, this review presents a brief description of the existing obstacles towards building genome‐scale kinetic models. Specific kinetic modeling frameworks capable of overcoming these obstacles are covered in this review. The tractability and physiological feasibility of these models are discussed with the objective of using available in vivo experimental observations to define the model parameter space. Among the different methods discussed, Monte Carlo kinetic models of metabolism stand out as potentially tractable methods to model genome scale networks while also addressing in vivo parameter uncertainty. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology Journal Wiley

Constructing kinetic models of metabolism at genome‐scales: A review

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References (97)

Publisher
Wiley
Copyright
Copyright © 2015 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1860-6768
eISSN
1860-7314
DOI
10.1002/biot.201400522
pmid
26332243
Publisher site
See Article on Publisher Site

Abstract

Constraint‐based modeling of biological networks (metabolism, transcription and signal transduction), although used successfully in many applications, suffer from specific limitations such as the lack of representation of metabolite concentrations and enzymatic regulation, which are necessary for a complete physiologically relevant model. Kinetic models conversely overcome these shortcomings and enable dynamic analysis of biological systems for enhanced in silico hypothesis generation. Nonetheless, kinetic models also have limitations for modeling at genome‐scales chiefly due to: (i) model non‐linearity; (ii) computational tractability; (iii) parameter identifiability; (iv) estimability; and (v) uncertainty. In order to support further development of kinetic models as viable alternatives to constraint‐based models, this review presents a brief description of the existing obstacles towards building genome‐scale kinetic models. Specific kinetic modeling frameworks capable of overcoming these obstacles are covered in this review. The tractability and physiological feasibility of these models are discussed with the objective of using available in vivo experimental observations to define the model parameter space. Among the different methods discussed, Monte Carlo kinetic models of metabolism stand out as potentially tractable methods to model genome scale networks while also addressing in vivo parameter uncertainty.

Journal

Biotechnology Journal – Wiley

Published: Sep 1, 2015

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