MapMi: automated mapping of microRNA loci

Abstract

Background: A large effort to discover microRNAs (miRNAs) has been under way. Currently miRBase is their primary repository, providing annotations of primary sequences, precursors and probable genomic loci. In many cases miRNAs are identical or very similar between related (or in some cases more distant) species. However, miRBase focuses on those species for which miRNAs have been directly confirmed. Secondly, specific miRNAs or their loci are sometimes not annotated even in well-covered species. We sought to address this problem by developing a computational system for automated mapping of miRNAs within and across species. Given the sequence of a known miRNA in one species it is relatively straightforward to determine likely loci of that miRNA in other species. Our primary goal is not the discovery of novel miRNAs but the mapping of validated miRNAs in one species to their most likely orthologues in other species.

Results: We present MapMi, a computational system for automated miRNA mapping across and within species. This method has a sensitivity of 92.20% and a specificity of 97.73%. Using the latest release (v14) of miRBase, we obtained 10,944 unannotated potential miRNAs when MapMi was applied to all 21 species in Ensembl Metazoa release 2 and 46 species from Ensembl release 55.

Conclusions: The pipeline and an associated web-server for mapping miRNAs are freely available on http://www.ebi.ac.uk/enright-srv/MapMi/. In addition precomputed miRNA mappings of miRBase miRNAs across a large number of species are provided.

Figure 1

MapMi Webserver Work flow. Work flow of the MapMi web pipeline. The user can use the service by either providing a potential mature sequence to map, or by querying the results database, either with a miRNA name or a job id if retrieving results from a previous run.

Figure 2

Heatmap of Drosophilid miRNAs. This figure was generated from a presence/absence matrix, it is color coded to illustrate the effect of mapping using MapMi in the overall view of miRNAs in the species under analysis. Dark purple corresponds to an overlap between MapMi predictions and miRBase annotation. Blue indicates miRNAs that are only present in MapMi, while green indicates miRNAs that are on miRBase but are missing from the MapMi predictions. Bias towards model organisms is readily apparent in this view. It is also clear from the image that MapMi is complementing miRBase in a way that is broadly coherent with the expected evolution of miRNAs across the metazoan lineage. The different species are ordered respecting their phylogenetic relationships, as present in the NCBI taxonomy.

Figure 3

Heatmap of Drosophilid miRNAs. Heatmap and hierarchical clustering of miRNAs present in the 12 drosophilid genomes, as predicted by MapMi using D. melanogaster miRNAs as query. Dendrograms produced by clustering of the data matrix. Dark blue indicates a miRNA present both in MapMi and in miRBase, light blue indicates a miRNA present in only one of the sets.