CiteULike: heliopais's Frey

Using expression profiling data to identify human microRNA targets

Jim Huang — 2007-11-29T18:47:18-00:00

Nat Meth, Vol. 4, No. 12. (December 2007), pp. 1045-1049.

Bayesian Inference of MicroRNA Targets from Sequence and Expression Data.

Jim Huang — 2007-08-10T06:54:52-00:00

Journal of Computational Biology, Vol. 14, No. 5. (June 2007), pp. 550-563.

MicroRNAs (miRNAs) regulate a large proportion of mammalian genes by hybridizing to targeted messenger RNAs (mRNAs) and down-regulating their translation into protein. Although much work has been done in the genome-wide computational prediction of miRNA genes and their target mRNAs, an open question is how to efficiently obtain functional miRNA targets from a large number of candidate miRNA targets predicted by existing computational algorithms. In this paper, we propose a novel Bayesian model and learning algorithm, GenMiR++ (Generative model for miRNA regulation), that accounts for patterns of gene expression using miRNA expression data and a set of candidate miRNA targets. A set of high-confidence functional miRNA targets are then obtained from the data using a Bayesian learning algorithm. Our model scores 467 high-confidence miRNA targets out of 1,770 targets obtained from TargetScanS in mouse at a false detection rate of 2.5%: several confirmed miRNA targets appear in our high-confidence set, such as the interactions between miR-92 and the signal transduction gene MAP2K4, as well as the relationship between miR-16 and BCL2, an anti-apoptotic gene which has been implicated in chronic lymphocytic leukemia. We present results on the robustness of our model showing that our learning algorithm is not sensitive to various perturbations of the data. Our high-confidence targets represent a significant increase in the number of miRNA targets and represent a starting point for a global understanding of gene regulation.

Comparing sequence and expression for predicting microRNA targets using GenMiR3.

JC Huang — 2008-03-04T12:13:24-00:00

Pacific Symposium in Biocomputing (24 September 2007), pp. 52-63.

We present a new model and learning algorithm, GenMiR3, which takes into account mRNA sequence features in addition to paired mRNA and miRNA expression profiles when scoring candidate miRNA-mRNA interactions. We evaluate three candidate sequence features for predicting miRNA targets by assessing the expression support for the predictions of each feature and the consistency of Gene Ontology Biological Process annotation of their target sets. We consider as sequence features the total energy of hybridization between the microRNA and target, conservation of the target site and the context score which is a composite of five individual sequence features. We demonstrate that only the total energy of hybridization is predictive of paired miRNA and mRNA expression data and Gene Ontology enrichment but this feature adds little to the total accuracy of GenMiR3 predictions using for expression features alone.