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

Abstract 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 repre...

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Main Authors: Hagai Levi, Ran Elkon, Ron Shamir
Format: Article
Language:English
Published: Springer Nature 2021-01-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20209593
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author Hagai Levi
Ran Elkon
Ron Shamir
author_facet Hagai Levi
Ran Elkon
Ron Shamir
author_sort Hagai Levi
collection DOAJ
description Abstract 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 https://github.com/Shamir‐Lab.
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spelling doaj.art-140b0bff945245639cc00108c60975042024-03-02T12:43:10ZengSpringer NatureMolecular Systems Biology1744-42922021-01-01171n/an/a10.15252/msb.20209593DOMINO: a network‐based active module identification algorithm with reduced rate of false callsHagai Levi0Ran Elkon1Ron Shamir2The Blavatnik School of Computer Science Tel Aviv University Tel Aviv IsraelDepartment of Human Molecular Genetics and Biochemistry Sackler School of Medicine Tel Aviv University Tel Aviv IsraelThe Blavatnik School of Computer Science Tel Aviv University Tel Aviv IsraelAbstract 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 https://github.com/Shamir‐Lab.https://doi.org/10.15252/msb.20209593biological networksenrichment analysisGO termsmodule discoveryomics
spellingShingle Hagai Levi
Ran Elkon
Ron Shamir
DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
Molecular Systems Biology
biological networks
enrichment analysis
GO terms
module discovery
omics
title DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
title_full DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
title_fullStr DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
title_full_unstemmed DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
title_short DOMINO: a network‐based active module identification algorithm with reduced rate of false calls
title_sort domino a network based active module identification algorithm with reduced rate of false calls
topic biological networks
enrichment analysis
GO terms
module discovery
omics
url https://doi.org/10.15252/msb.20209593
work_keys_str_mv AT hagailevi dominoanetworkbasedactivemoduleidentificationalgorithmwithreducedrateoffalsecalls
AT ranelkon dominoanetworkbasedactivemoduleidentificationalgorithmwithreducedrateoffalsecalls
AT ronshamir dominoanetworkbasedactivemoduleidentificationalgorithmwithreducedrateoffalsecalls