Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-59822

Zamora-Sillero, E; Hafner, M; Ibig, A; Stelling, J; Wagner, A (2011). Efficient characterization of high-dimensional parameter spaces for systems biology. BMC Systems Biology, 5:142.

[img]
Preview
Published Version
PDF
2MB

View at publisher

Abstract

BACKGROUND: A biological system's robustness to mutations and its evolution are influenced by the structure of its viable space, the region of its space of biochemical parameters where it can exert its function. In systems with a large number of biochemical parameters, viable regions with potentially complex geometries fill a tiny fraction of the whole parameter space. This hampers explorations of the viable space based on "brute force" or Gaussian sampling.

RESULTS: We here propose a novel algorithm to characterize viable spaces efficiently. The algorithm combines global and local explorations of a parameter space. The global exploration involves an out-of-equilibrium adaptive Metropolis Monte Carlo method aimed at identifying poorly connected viable regions. The local exploration then samples these regions in detail by a method we call multiple ellipsoid-based sampling. Our algorithm explores efficiently nonconvex and poorly connected viable regions of different test-problems. Most importantly, its computational effort scales linearly with the number of dimensions, in contrast to "brute force" sampling that shows an exponential dependence on the number of dimensions. We also apply this algorithm to a simplified model of a biochemical oscillator with positive and negative feedback loops. A detailed characterization of the model's viable space captures well known structural properties of circadian oscillators. Concretely, we find that model topologies with an essential negative feedback loop and a nonessential positive feedback loop provide the most robust fixed period oscillations. Moreover, the connectedness of the model's viable space suggests that biochemical oscillators with varying topologies can evolve from one another.

CONCLUSIONS: Our algorithm permits an efficient analysis of high-dimensional, nonconvex, and poorly connected viable spaces characteristic of complex biological circuitry. It allows a systematic use of robustness as a tool for model discrimination.

Citations

8 citations in Web of Science®
12 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 05 Mar 2012
13 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Evolutionary Biology and Environmental Studies
Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > YeastX
DDC:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:15 September 2011
Deposited On:05 Mar 2012 14:20
Last Modified:27 Nov 2013 16:46
Publisher:BioMed Central
ISSN:1752-0509
Publisher DOI:10.1186/1752-0509-5-142
PubMed ID:21920040

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page