title: BayMiR: inferring evidence for endogenous miRNA-induced gene repression from mRNA expression profiles.
abstract: BACKGROUND
  Popular miRNA target prediction techniques use sequence features to determine the functional miRNA target sites. These techniques commonly ignore the cellular conditions in which miRNAs interact with their targets in vivo. Gene expression data are rich resources that can complement sequence features to take into account the context dependency of miRNAs.
  
  
  RESULTS
  We introduce BayMiR, a new computational method, that predicts the functionality of potential miRNA target sites using the activity level of the miRNAs inferred from genome-wide mRNA expression profiles. We also found that mRNA expression variation can be used as another predictor of functional miRNA targets. We benchmarked BayMiR, the expression variation, Cometa, and the TargetScan "context scores" on two tasks: predicting independently validated miRNA targets and predicting the decrease in mRNA abundance in miRNA overexpression assays. BayMiR performed better than all other methods in both benchmarks and, surprisingly, the variation index performed better than Cometa and some individual determinants of the TargetScan context scores. Furthermore, BayMiR predicted miRNA target sets are more consistently annotated with GO and KEGG terms than similar sized random subsets of genes with conserved miRNA seed regions. BayMiR gives higher scores to target sites residing near the poly(A) tail which strongly favors mRNA degradation using poly(A) shortening. Our work also suggests that modeling multiplicative interactions among miRNAs is important to predict endogenous mRNA targets.
  
  
  CONCLUSIONS
  We develop a new computational method for predicting the target mRNAs of miRNAs. BayMiR applies a large number of mRNA expression profiles and successfully identifies the mRNA targets and miRNA activities without using miRNA expression data. The BayMiR package is publicly available and can be readily applied to any mRNA expression data sets.
authors.forename: Hossein
authors.initials: H
authors.lastname: Radfar
authors.forename: Willy
authors.initials: W
authors.lastname: Wong
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada. quaid.morris@utoronto.ca.
authors.forename: Quaid
authors.initials: Q
authors.lastname: Morris
mesh_terms: D020413:3' Untranslated Regions; D019295:Computational Biology / Q000379:methods*; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012984:Software; D059467:Transcriptome; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger