NDLI: Modeling Dynamic Regulatory Processes in Stroke

Content Provider	PubMed Central
Author	Mcdermott, Jason E. Jarman, Kenneth Taylor, Ronald Lancaster, Mary Shankaran, Harish Vartanian, Keri B. Stevens, Susan L. Stenzel-poore, Mary P. Sanfilippo, Antonio
Editor	Price, Nathan D.
Copyright Year	2012
Abstract	The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms.
Related Links	http://dx.doi.org/10.1371/journal.pcbi.1002722
Starting Page	1002722
File Format	PDF
ISSN	15537358
e-ISSN	15537358
Journal	PLoS Computational Biology
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2012-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Ecology Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics Computational Theory and Mathematics Cellular and Molecular Neuroscience Modeling and Simulation

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