靶分子的检测.pptVIP

Detecting MicroRNA Targets by Linking Sequence, MicroRNA and Gene Expression Data Joint work with Quaid Morris(2) and Brendan Frey(1),(2) Transcriptional regulation Post-transcriptional regulation Mechanisms for microRNA regulation Post-transcriptional degradation of target mRNA transcript microRNA triggers the destruction of target Mechanisms for microRNA regulation Toronto microRNA, mRNA and protein data TargetScanS microRNA target predictions Linking microRNA and mRNA expression 1,770 TargetScanS candidate targets linking 788 targeted mRNA transcripts to 22 microRNAs in 17 tissues Generative model for microRNA regulation The GenMiR method 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 Some notation A Bayesian network for detecting microRNA targets A probabilistic model for microRNA regulation A probabilistic model for microRNA regulation A probabilistic model for microRNA regulation A probabilistic model for microRNA regulation A probabilistic model for microRNA regulation Learning microRNA targets Maximize likelihood of observed data: Upper bound on negative log likelihood: Variational Inference Detecting microRNA targets Detecting microRNA targets Summary Evidence that microRNAs operate by degrading target mRNAs Model for combinatorial microRNA regulation High-throughput method for learning bona fide miRNA targets Full list of detected microRNA targets is available at /~GenMiR/ The road ahead… Differences in normalization and hybridization conditions in mRNA and microRNA data? Bayesian learning Robustness of model and learning algorithm to Subsampling of data? Introducing fake targets? Biological verification and network mining Sufficient statistics Variational Expectation-Maximization Variational EM updates Combinatorial microRNA regulation Robustnes