PMID- 28911111 OWN - NLM STAT- In-Process DA - 20170915 LR - 20170917 IS - 1362-4962 (Electronic) IS - 0305-1048 (Linking) VI - 45 IP - 15 DP - 2017 Sep 06 TI - Combinatorial ensemble miRNA target prediction of co-regulation networks with non-prediction data. PG - 8745-8757 LID - 10.1093/nar/gkx605 [doi] AB - MicroRNAs (miRNAs) are key regulators of cell-fate decisions in development and disease with a vast array of target interactions that can be investigated using computational approaches. For this study, we developed metaMIR, a combinatorial approach to identify miRNAs that co-regulate identified subsets of genes from a user-supplied list. We based metaMIR predictions on an improved dataset of human miRNA-target interactions, compiled using a machine-learning-based meta-analysis of established algorithms. Simultaneously, the inverse dataset of negative interactions not likely to occur was extracted to increase classifier performance, as measured using an expansive set of experimentally validated interactions from a variety of sources. In a second differential mode, candidate miRNAs are predicted by indicating genes to be targeted and others to be avoided to potentially increase specificity of results. As an example, we investigate the neural crest, a transient structure in vertebrate development where miRNAs play a pivotal role. Patterns of metaMIR-predicted miRNA regulation alone partially recapitulated functional relationships among genes, and separate differential analysis revealed miRNA candidates that would downregulate components implicated in cancer progression while not targeting tumour suppressors. Such an approach could aid in therapeutic application of miRNAs to reduce unintended effects. The utility is available at http://rna.informatik.uni-freiburg.de/metaMIR/. CI - (c) The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Davis, Jason A AU - Davis JA AD - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany. FAU - Saunders, Sita J AU - Saunders SJ AD - Bioinformatics Group, Department of Computer Science, Albert-Ludwigs-University Freiburg, Georges-Kohler-Allee 106, 79110 Freiburg, Germany. FAU - Mann, Martin AU - Mann M AD - Bioinformatics Group, Department of Computer Science, Albert-Ludwigs-University Freiburg, Georges-Kohler-Allee 106, 79110 Freiburg, Germany. FAU - Backofen, Rolf AU - Backofen R AD - Bioinformatics Group, Department of Computer Science, Albert-Ludwigs-University Freiburg, Georges-Kohler-Allee 106, 79110 Freiburg, Germany. AD - ZBSA Centre for Biological Systems Analysis, Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104 Freiburg, Germany. AD - BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, Albert-Ludwigs-University Freiburg, Germany. AD - Centre for non-coding RNA in Technology and Health, University of Copenhagen, Gr solidus in circlennegardsvej 3, DK-1870 Frederiksberg C, Denmark. LA - eng PT - Journal Article PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 PMC - PMC5587804 EDAT- 2017/09/16 06:00 MHDA- 2017/09/16 06:00 CRDT- 2017/09/16 06:00 PHST- 2016/11/24 [received] PHST- 2017/07/06 [accepted] AID - 3958712 [pii] AID - 10.1093/nar/gkx605 [doi] PST - ppublish SO - Nucleic Acids Res. 2017 Sep 6;45(15):8745-8757. doi: 10.1093/nar/gkx605.