Assessing Computational Methods of Cis-Regulatory Module Prediction 英文参考文献.docVIP

AssessingComputationalMethodsofCis-Regulatory ModulePrediction JingSu1*,SarahA.Teichmann1,ThomasA.Down2* 1MRCLaboratoryofMolecularBiology,Cambridge,UnitedKingdom,2TheWellcomeTrust/CancerResearchUKGurdonInstitute,UniversityofCambridge,Cambridge, UnitedKingdom Abstract Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specificinteractionsinvolvedremainslimited.Withoutacomprehensivecomparisonoftheirperformance,thereliabilityand accuracy of these tools remains unclear. Faced with a large number of different tools that address this problem, we summarizedandcategorizedthembasedonsearchstrategyandinputdatarequirements.Twelverepresentativemethods were chosen and applied to predict CRMs from the Drosophila CRM database REDfly, and across the human ENCODE regions. Our results show that the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied.Weanalyzetheprincipalfeaturesthatdistinguishthemethodsthatperformedwell,identifyweaknessesleadingto poorperformance,andprovideaguideforusers.Wealsoproposekeyconsiderationsforthedevelopmentandevaluation offutureCRM-predictionmethods. Citation: Su J, Teichmann SA, Down TA (2010) Assessing Computational Methods of Cis-Regulatory Module Prediction. PLoS Comput Biol 6(12): e1001020.