Reverse Engineering a Signaling Network Using Alternative Inputs 英文参考文献.docVIP

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Reverse Engineering a Signaling Network Using Alternative Inputs 英文参考文献.doc

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Reverse Engineering a Signaling Network Using Alternative Inputs 英文参考文献

ReverseEngineeringaSignalingNetworkUsing AlternativeInputs HiromasaTanaka1,2,Tau-MuYi1,2 * 1Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America, 2Center for Complex Biological Systems, UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract One of the goals of systems biology is to reverse engineer in a comprehensive fashion the arrow diagrams of signal transduction systems. An important tool for ordering pathway components is genetic epistasis analysis, and here we presentastrategytermedAlternativeInputs(AIs)toperformsystematicepistasisanalysis.Analternativeinputisdefinedas anygeneticmanipulationthatcanactivatethesignalingpathwayinsteadofthenaturalinput.Weintroducedtheconcept of an ‘‘AIs-Deletions matrix’’ that summarizes the outputs of all combinations of alternative inputs and deletions. We developedthetheoryandalgorithmstoconstructapairwiserelationshipgraphfromtheAIs-Deletionsmatrixcapturing both functional ordering (upstream, downstream) and logical relationships (AND, OR), and then interpreting these relationships into a standard arrow diagram. As a proof-of-principle, we applied this methodology to a subset of genes involvedinyeastmatingsignaling.Thisexperimentalpilotstudyhighlightstherobustnessoftheapproachandimportant technicalchallenges.Insummary,thisresearchformalizesandextendsclassicalepistasisanalysisfromlinearpathwaysto morecomplexnetworks,facilitatingcomputationalanalysisandreconstructionofsignalingarrowdiagrams. Citation:TanakaH,YiT-M(2009)ReverseEngineeringaSignalingNetworkUsingAlternativeInputs.PLoSONE4(10):e7622.doi:10.1371/journal.pone.0007622 Editor:MarkIsalan,CenterforGenomicRegulation,Spain ReceivedAugust28,2009;AcceptedOctober6,2009;PublishedOctober29,2009 Copyright: ? 2009 Tanaka, Yi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninany