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Bioinformatics. 2019 Aug 29. pii: btz675. doi: 10.1093/bioinformatics/btz675. [Epub ahead of print]

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

Author information

Institute of Neuroscience, University of Oregon, Eugene OR, USA.
Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA, USA.
University of Utah, Biomedical Informatics, UT, USA.
Department of Control and Computer Engineering, Politecnico di Torino, Italy.
Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Computational Epigenomics Lab., Genetics Department & Biotechnology Institute & Biosanitary Institute, University of Granada, Spain.
Department of Biostatistics, Harvard T.H. Chan School of Public Health. Boston, MA, USA.
Universitat Oberta de Catalunya. Spain.
Sorbonne Université, Pierre Louis Doctoral School of Public Health, Paris, France.
Institut National pour la Santé et la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMR_S), Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.
RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD.
Non-coding Research Lab, Cancer Research Institute | Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bioinformatics Core, The Picower Institute for Learning and Memory, MA, USA.



MicroRNAs (miRNAs) are small RNA molecules (∼22 nucleotide long) involved in post-transcriptional 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, the diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods.


To overcome this situation, we present here a community-based project, miRTOP (miRNA Transcriptomic Open Project) working towards the optimization of miRNA analyses. The aim of miRTOP is to promote the development of downstream isomiR analysis tools that are compatible with existing detection and quantification tools. Based on the existing GFF3 format, we first created a new standard format, mirGFF3, for the output of miRNA/isomiR detection and quantification results from small RNA-seq data. Additionally, we developed a command line Python tool, mirtop, to create and manage the mirGFF3 format. Currently, mirtop can convert into mirGFF3 the outputs of commonly used pipelines, such as seqbuster, isomiR-SEA, sRNAbench, Prost! as well as BAM files. Some tools have also incorporated the mirGFF3 format directly into their code, such as, miRge2.0, IsoMIRmap, and OptimiR. Its open architecture enables any tool or pipeline to output or convert results into mirGFF3. Collectively, this isomiR categorization system, along with the accompanying mirGFF3 and mirtop API, provide a comprehensive solution for the standardization of miRNA and isomiR annotation, enabling data sharing, reporting, comparative analyses, and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps of miRNA detection, annotation, and quantification.



Supplementary data are available at Bioinformatics online.

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