miRNA 靶分子的检测PPT.ppt

04/02/2006 RECOMB 2006 RECOMB 2006 Detecting MicroRNA Targets by Linking Sequence, MicroRNA and Gene Expression Data Joint work with Quaid Morris(2) and Brendan Frey(1),(2) Jim Huang(1) Probabilistic and Statistical Inference Group, Edward S. Rogers Department of Electrical and Computer Engineering, University of Toronto Banting Best Department of Medical Research, University of Toronto Transcriptional regulation Transcription and splicing mRNA transcript Protein- coding gene Transcription factor Post-transcriptional regulation Mature microRNA microRNA target site RISC mRNA transcript Silencing microRNA gene Finding microRNA targets Lots of targets: are they all real? IDEA: Use high-throughput data to find bona fide targets Mature microRNA microRNA target site RISC mRNA transcript Silencing Expression Down-regulation Post-transcriptional degradation of target mRNA transcript microRNA triggers the destruction of target Mechanisms for microRNA regulation Translational repression microRNA prevents translation to protein RISC Transcription RISC Transcription Translation 1,770 TargetScanS candidate targets linking 788 targeted mRNA transcripts to 22 microRNAs in 17 tissues Linking microRNA and mRNA expression miR-16/Spleen Expression of putative targets Background expression p 10-7 GenMiR Generative model for microRNA regulation Get candidate targets microRNA sequence data mRNA sequence data microRNA expression data mRNA expression data Detected microRNA targets GCATCAT AACTGCA … Observed: Set of candidate microRNA targets microRNA expression data mRNA expression data Unobserved: Indicator variables Model parameters: Regulatory weight for each microRNA Background level of mRNA expression The GenMiR method Some notation messengerRNA microRNA Indicator variable for whether microRNA k truly targets mRNA g regulatory weight Indicator of putative interaction between microRNA k and target transcript g A Bayesian