Van Du T Tran1, Sébastien Moretti1,2, Alix T Coste3, Sara Amorim-Vaz3, Dominique Sanglard3, Marco Pagni1. 1. Vital-IT Group, SIB Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. 2. Evolutionary Bioinformatics Group, SIB Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. 3. Institute of Microbiology, University Hospital and University of Lausanne, CH-1015 Lausanne, Switzerland.
Abstract
MOTIVATION: Genome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism's metabolism, yet their integration to achieve biological insight remains challenging. RESULTS: We investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO. AVAILABILITY AND IMPLEMENTATION: The metaboGSE R package is available at https://CRAN.R-project.org/package=metaboGSE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Genome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism's metabolism, yet their integration to achieve biological insight remains challenging. RESULTS: We investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO. AVAILABILITY AND IMPLEMENTATION: The metaboGSE R package is available at https://CRAN.R-project.org/package=metaboGSE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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