Velandia-Huerto, Cristian A.; Jorg Fallmann and Peter F. Stadler

Homology-based annotation of short RNAs, including microRNAs, is a difficult problem because their inherently small size limits the available information. Highly sensitive methods, including parameter optimized blast, nhmmer, or cmsearch runs designed to increase sensitivity inevitable lead to large numbers of false positives, which can be detected only by detailed analysis of specific features typical for a RNA family and/or the analysis of conservation patterns in structure-annotated multiple sequence alignments. The miRNAture pipeline implements a workflow specific to animal microRNAs that automatizes homology search and validation steps. The miRNAture pipeline yields very good results for a large number of "typical" miRBase families. However, it also highlights difficulties with atypical cases, in particular microRNAs deriving from repetitive elements and microRNAs with unusual, branched precursor structures and atypical locations of the mature product, which require specific curation by domain experts.