Priming nonlinear searches for pathway identification

Theoretical Biology & Medical Modelling
Siren R VeflingstadEberhard O Voit

Abstract

Dense time series of metabolite concentrations or of the expression patterns of proteins may be available in the near future as a result of the rapid development of novel, high-throughput experimental techniques. Such time series implicitly contain valuable information about the connectivity and regulatory structure of the underlying metabolic or proteomic networks. The extraction of this information is a challenging task because it usually requires nonlinear estimation methods that involve iterative search algorithms. Priming these algorithms with high-quality initial guesses can greatly accelerate the search process. In this article, we propose to obtain such guesses by preprocessing the temporal profile data and fitting them preliminarily by multivariate linear regression. The results of a small-scale analysis indicate that the regression coefficients reflect the connectivity of the network quite well. Using the mathematical modeling framework of Biochemical Systems Theory (BST), we also show that the regression coefficients may be translated into constraints on the parameter values of the nonlinear BST model, thereby reducing the parameter search space considerably. The proposed method provides a good approach for obtaining...Continue Reading

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Citations

Oct 14, 2006·Bioinformatics·Orland R GonzalezEduardo Mendoza
Feb 5, 2009·Bioinformatics·Shuhei KimuraMariko Hatakeyama
Feb 7, 2006·BMC Bioinformatics·Bor-Sen Chen, Yu-Chao Wang
Jan 16, 2008·BMC Bioinformatics·Shuhei KimuraMariko Hatakeyama
Jul 19, 2006·Theoretical Biology & Medical Modelling·Tomoya KitayamaMasaru Tomita
Jul 21, 2006·Theoretical Biology & Medical Modelling·I-Chun ChouEberhard O Voit
Jan 31, 2006·Theoretical Biology & Medical Modelling·Pradeep K PolisettyEdward P Gatzke
Jan 25, 2011·BMC Systems Biology·Choujun Zhan, Lam F Yeung
Jul 11, 2012·BMC Systems Biology·I-Chun Chou, Eberhard O Voit
Dec 2, 2009·IET Systems Biology·E O VoitL L Fonseca
Feb 14, 2008·IEEE Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the IEEE Systems, Man, and Cybernetics Society·Bor-Sen ChenYu-Chao Wang
Sep 9, 2006·Journal of Bioinformatics and Computational Biology·Simeone Marino, Eberhard O Voit
Nov 27, 2016·Arthropod Structure & Development·Bo-Kai Liao, Andrew C Oates
Jan 6, 2010·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Brett A McKinney
Jan 1, 2008·Biotechnology & Genetic Engineering Reviews·Rui AlvesAlbert Sorribas

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR

Software Mentioned

GMA
systems

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