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Automatic Context-Specific Subnetwork Discovery from Large Interaction Networks.doc

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Automatic Context-Specific Subnetwork Discovery from Large Interaction Networks

AutomaticContext-SpecificSubnetworkDiscoveryfrom LargeInteractionNetworks AshisSaha1,AikChoonTan2,JaewooKang1,3* 1Department of Computer Science and Engineering, Korea University, Seoul, Korea, 2Department of Medicine/Medical Oncology, University of Colorado Anschutz MedicalCampus,Aurora,Colorado,UnitedStatesofAmerica,3InterdisciplinaryGraduatePrograminBioinformatics,KoreaUniversity,Seoul,Korea Abstract Genesactinconcertviaspecificnetworkstodrivevariousbiologicalprocesses,includingprogressionofdiseasessuchas cancer.Underdifferentphenotypes,differentsubsetsofthegenemembersofanetworkparticipateinabiologicalprocess. Singlegeneanalysesarelesseffectiveinidentifyingsuchcoregenemembers(subnetworks)withinageneset/network,as comparedtogeneset/network-basedanalyses.Hence,itisusefultoidentifyadiscriminativeclassifierbyfocusingonthe subnetworks that correspond to different phenotypes. Here we present a novel algorithm to automatically discover the important subnetworks of closely interacting molecules to differentiate between two phenotypes (context) using gene expression profiles. We name it COSSY (COntext-Specific Subnetwork discoverY). It is a non-greedy algorithm and thus unlikelytohavelocaloptimaproblems.COSSYworksforanyinteractionnetworkregardlessofthenetworktopology.One addedbenefitofCOSSYisthatitcanalsobeusedasahighlyaccurateclassificationplatformwhichcanproduceasetof interpretablefeatures. Citation:SahaA,TanAC,KangJ(2014)AutomaticContext-SpecificSubnetworkDiscoveryfromLargeInteractionNetworks.PLoSONE9(1):e84227.doi:10.1371/ journal.pone.0084227 Editor:PatrickAloy,InstituteforResearchinBiomedicine,Spain ReceivedSeptember10,2013;AcceptedNovember21,2013;PublishedJanuary1,2014 Copyright: ? 2014 Saha etal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by the Nationa