Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 17, Issue 1, Pages -Publisher
WILEY
DOI: 10.15252/msb.20209593
Keywords
biological networks; enrichment analysis; GO terms; module discovery; omics
Categories
Funding
- German-Israeli Project [DFG RE 4193/1-1]
- Israel Science Foundation [1339/18, 2118/19]
- Len Blavatnik And The Blavatnik Family Foundation
- Koret-UC Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics
- Edmond J. Safra Center for Bioinformatics at Tel Aviv University
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Algorithms for active module identification (AMI) analyze gene networks and activity scores to identify active modules representing key biological processes. However, these methods often report modules not specific to the analyzed biological context. To address this bias, a permutation-based method was developed to evaluate GO terms reported by AMI methods. The novel AMI algorithm, DOMINO, outperformed other algorithms in testing on GE and GWAS data.
Algorithms for active module identification (AMI) are central to analysis of omics data. Such algorithms receive a gene network and nodes' activity scores as input and report subnetworks that show significant over-representation of accrued activity signal (active modules), thus representing biological processes that presumably play key roles in the analyzed conditions. Here, we systematically evaluated six popular AMI methods on gene expression and GWAS data. We observed that GO terms enriched in modules detected on the real data were often also enriched on modules found on randomly permuted data. This indicated that AMI methods frequently report modules that are not specific to the biological context measured by the analyzed omics dataset. To tackle this bias, we designed a permutation-based method that empirically evaluates GO terms reported by AMI methods. We used the method to fashion five novel AMI performance criteria. Last, we developed DOMINO, a novel AMI algorithm, that outperformed the other six algorithms in extensive testing on GE and GWAS data. Software is available at .
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