Journal
BRIEFINGS IN BIOINFORMATICS
Volume 21, Issue 6, Pages 1875-1885Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbz094
Keywords
elementary flux modes; elementary flux mode analysis; pathway analysis; parallel computing; scalability
Funding
- National Science Foundation [1909536]
- National Institute Of General Medical Sciences of the National Institutes of Health [R01GM132391]
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [1909536] Funding Source: National Science Foundation
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While elementary flux mode (EFM) analysis is now recognized as a cornerstone computational technique for cellular pathway analysis and engineering, EFM application to genome-scale models remains computationally prohibitive. This article provides a review of aspects of EFM computation that elucidates bottlenecks in scaling EFM computation. First, algorithms for computing EFM5 are reviewed. Next, the impact of redundant constraints, sensitivity to constraint ordering and network compression are evaluated. Then, the advantages and limitations of recent parallelization and GPU-based efforts are highlighted. The article then reviews alternative pathway analysis approaches that aim to reduce the EFM solution space. Despite advances in EFM computation, our review concludes that continued scaling of EFM computation is necessary to apply EFM to genome-scale models. Further, our review concludes that pathway analysis methods that target specific pathway properties can provide powerful alternatives to EFM analysis.
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