MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data

Abstract

Transfer RNA fragments (tRFs) are an established class of constitutive regulatory molecules that arise from precursor and mature tRNAs. RNA deep sequencing (RNA-seq) has greatly facilitated the study of tRFs. However, the repeat nature of the tRNA templates and the idiosyncrasies of tRNA sequences necessitate the development and use of methodologies that differ markedly from those used to analyze RNA-seq data when studying microRNAs (miRNAs) or messenger RNAs (mRNAs). Here we present MINTmap (for MItochondrial and Nuclear TRF mapping), a method and a software package that was developed specifically for the quick, deterministic and exhaustive identification of tRFs in short RNA-seq datasets. In addition to identifying them, MINTmap is able to unambiguously calculate and report both raw and normalized abundances for the discovered tRFs. Furthermore, to ensure specificity, MINTmap identifies the subset of discovered tRFs that could be originating outside of tRNA space and flags them as candidate false positives. Our comparative analysis shows that MINTmap exhibits superior sensitivity and specificity to other available methods while also being exceptionally fast. The MINTmap codes are available through https://github.com/TJU-CMC-Org/MINTmap/ under an open source GNU GPL v3.0 license.

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

“…The proper identification of isomiRs between studies is still an open problem, since different tools and research groups utilize different nomenclatures and representations. To this end, we adopted a unique identifier (UID), or 'IsomiR license plate', inspired by the MINTmap approach for tRNA fragments [52,53] and acting as a sequence-dependent unique ID that is independent of genome assembly and doesn't require a brokering naming mechanism. Any isomiR sequence can be mapped to a UID and any UID can be converted back to the isomiR sequence it represents ( Figure 1B).…”

Angiogenin promotes colorectal cancer metastasis via tiRNA production

“…For tsRNA analysis, reads were annotated using MINTmap software on GitHub and further processed using the BioData R package. 21 To determine differentially expressed tsRNAs in CRC tumor tissue and paired adjacent tissue, each fragment sequence was grouped according to tRNA isoacceptor, origin and length according to MINTmap annotation. The statistical significance of the difference may be conveniently estimated by Student's ttest.…”

Large differences in small RNA composition between human biofluids

“…Transfer RNA-derived RNAs (tDRs) are generated by cleavage of tRNAs at specific sites (Gebetsberger and Polacek, 2013). The variety of tDRs is extensive since there are many (>600) human tRNA genes and multiple fragment types, including 5'-halves, 3'-halves, 5'-tRNA-fragments (tRFs), 3'-tRFs, and internal tRFs (i-tRFs) have been identified (Loher et al, 2017). Small RNAs derived from mRNAs, long non-coding RNAs, ribosomal RNAs (Semenov et al, 2004), and Y RNAs (Dhahbi et al, 2013) have also been detected in some biofluids.…”