Complete enumeration of elementary flux modes through scalable demand-based subnetwork definition

• DOI: 10.1093/bioinformatics/btu021
• Publication Date: 2014-02-05T01:26:48Z
• Authors: Kristopher A. Hunt; James P. Folsom; Reed L. Taffs; Ross P. Carlson
• Keywords: Flux Balance Analysis; Enumeration; Metabolic network; Subnetwork

Abstract Motivation: Elementary flux mode analysis (EFMA) decomposes complex metabolic network models into tractable biochemical pathways, which have been used for rational design and of regulatory networks. However, application EFMA has often limited to targeted or simplified representations due computational demands the method. Results: Division biological networks subnetworks enables complete enumeration elementary modes (EFMs) a broad range complexities, including genome-scale. Here, are defined using serial dichotomous suppression enforcement through model reactions. Rules selecting appropriate reactions generate proposed tested; three test cases, both prokaryotic eukaryotic models, verify efficacy these rules demonstrate completeness reproducibility EFM enumeration. is demand-based automated; computationally intractable further divided until entire solution space enumerated. To strategy’s scalability, splitting algorithm was implemented an software package (EFMTool) Windows PowerShell on 50 node Microsoft high performance computing cluster. Enumeration EFMs in genome-scale diatom, Phaeodactylum tricornutum, identified ∼2 billion EFMs. The output represents order magnitude increase computed compared with other published algorithms demonstrates scalable framework most systems. Availability implementation: http://www.chbe.montana.edu/RossC. Contact: [e-mail] [e-mail] Supplementary Information: Supplemental materials available at Bioinformatics online.