Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API

Abstract

Background:MicroRNAs (miRNAs) are small RNA molecules (~22 nucleotide long) involved in posttranscriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, a lack of consensus on miRNA/isomiR analyses exists, and the resulting diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods. Conclusions:Collectively a comprehensive isomiR categorization system, along with the accompanying mirGFF3 and mirtop API provide a complete solution for the standardization of miRNA and isomiR analysis, enabling data sharing, reporting, comparative analyses, and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps to miRNA detection, annotation, and quantification.

On the expanding roles of tRNA fragments in modulating cell behavior

“…In fact, there is currently no standardized nomenclature for tRFs. This is unlike the class of microRNAs (miRNAs), where a recent multi-team effort recognized a similar need for standardization and proposed a universal scheme for labeling miRNA isoforms ( 48 , 49 ), which we discuss below.…”

“…Lastly, it is worth pointing out that the license-plate labeling scheme can be extended to other types of short RNAs. For example, it was adopted by the recently-proposed standard for labeling, reporting, and comparing miRNA isoforms, which are known as isomiRs ( 48 ). As with the tRFs, the rules remain the same with the exception of the prefix, which now is ‘iso-’ (instead of ‘tRF-’).…”

“…For human tissues, Rigoutsos and colleagues published the first explorations of the links between tRFs and homeostasis or disease, and reported on the expression profiles of tRFs in lymphoblastoid cells derived from healthy individuals and in multiple subtypes of breast cancer ( 37 , 57 ). Since then, they have also discussed tRFs in prostate cancer ( 56 ), uveal melanoma ( 54 ), lung cancer ( 48 ), bladder cancer ( 48 ), and kidney cancer ( 48 ). In the case of uveal melanoma, they showed that tRFs are linked to overall survival ( 54 ).…”

OPTIMIR, a novel algorithm for integrating available genome-wide genotype data into miRNA sequence alignment analysis

“…The files generated by OPTIMIR include (i) global abundances of miRNAs (counts of isomiRs and polymiRs are merged with the reference mature sequences' counts); (ii) specific abundances for each polymiR sequence; (iii) specific abundances for each isomiR sequence; (iv) alignments that are inconsistent with provided genotypes; (v) two annotation files containing details on templated nucleotides and alignments that could not be disambiguated. In addition, OPTIMIR allows to generate its results into the recently developed mirGFF3 format (Desvignes et al 2018) aimed at unifying results of any miRSeq data analysis.…”

OPTIMIR, a novel algorithm for integrating available genome-wide genotype data into miRNA sequence alignment analysis

“…The files generated by OPTIMIR include: 1/ global abundances of miRNAs (counts of isomiRs and polymiRs are merged with the reference mature sequences' counts); 2/ specific abundances for each polymiR sequence; 3/ specific abundances for each isomiR sequence; 4/ alignments that are inconsistent with provided genotypes; 5/ two annotation files containing details on templated nucleotides and alignments that could not be disambiguated. In addition, OPTIMIR allows to generate its results into the recently developed mirGFF3 format (Desvignes et al, 2018) aimed at unifying results of any miRSeq data analysis.…”