title: Using expression profiling data to identify human microRNA targets.
abstract: We demonstrate that paired expression profiles of microRNAs (miRNAs) and mRNAs can be used to identify functional miRNA-target relationships with high precision. We used a Bayesian data analysis algorithm, GenMiR++, to identify a network of 1,597 high-confidence target predictions for 104 human miRNAs, which was supported by RNA expression data across 88 tissues and cell types, sequence complementarity and comparative genomics data. We experimentally verified our predictions by investigating the result of let-7b downregulation in retinoblastoma using quantitative reverse transcriptase (RT)-PCR and microarray profiling: some of our verified let-7b targets include CDC25A and BCL7A. Compared to sequence-based predictions, our high-scoring GenMiR++ predictions had much more consistent Gene Ontology annotations and were more accurate predictors of which mRNA levels respond to changes in let-7b levels.
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, Ontario M5S 3G4, Canada.
authors.forename: Jim C
authors.initials: JC
authors.lastname: Huang
authors.forename: Tomas
authors.initials: T
authors.lastname: Babak
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
authors.forename: Gordon
authors.initials: G
authors.lastname: Chua
authors.forename: Sofia
authors.initials: S
authors.lastname: Khan
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Frey
authors.forename: Quaid D
authors.initials: QD
authors.lastname: Morris
mesh_terms: D001483:Base Sequence; D020869:Gene Expression Profiling / Q000379:methods*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: D035683:MicroRNAs