DOMINO: a network-based active module identification algorithm with reduced rate of false calls

Hagai Levi, Ran Elkon, Ron Shamir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Article numbere9593
JournalMolecular Systems Biology
Issue number1
StatePublished - Jan 2021


  • GO terms
  • biological networks
  • enrichment analysis
  • module discovery
  • omics


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