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.2016 Aug 15;32(16):2481-9.
doi: 10.1093/bioinformatics/btw194. Epub 2016 Apr 13.

MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments

Affiliations

MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments

Venetia Pliatsika et al. Bioinformatics..

Abstract

Motivation: It has been known that mature transfer RNAs (tRNAs) that are encoded in the nuclear genome give rise to short molecules, collectively known as tRNA fragments or tRFs. Recently, we reported that, in healthy individuals and in patients, tRFs are constitutive, arise from mitochondrial as well as from nuclear tRNAs, and have composition and abundances that depend on a person's sex, population origin and race as well as on tissue, disease and disease subtype. Our findings as well as similar work by other groups highlight the importance of tRFs and presage an increase in the community's interest in elucidating the roles of tRFs in health and disease.

Results: We created MINTbase, a web-based framework that serves the dual-purpose of being a content repository for tRFs and a tool for the interactive exploration of these newly discovered molecules. A key feature of MINTbase is that it deterministically and exhaustively enumerates all possible genomic locations where a sequence fragment can be found and indicates which fragments are exclusive to tRNA space, and thus can be considered as tRFs: this is a very important consideration given that the genomes of higher organisms are riddled with partial tRNA sequences and with tRNA-lookalikes whose aberrant transcripts can be mistaken for tRFs. MINTbase is extremely flexible and integrates and presents tRF information from multiple yet interconnected vantage points ('vistas'). Vistas permit the user to interactively personalize the information that is returned and the manner in which it is displayed. MINTbase can report comparative information on how a tRF is distributed across all anticodon/amino acid combinations, provides alignments between a tRNA and multiple tRFs with which the user can interact, provides details on published studies that reported a tRF as expressed, etc. Importantly, we designed MINTbase to contain all possible tRFs that could ever be produced by mature tRNAs: this allows us to report on their genomic distributions, anticodon/amino acid properties, alignments, etc. while giving users the ability to at-will investigate candidate tRF molecules before embarking on focused experimental explorations. Lastly, we also introduce a new labeling scheme that is tRF-sequence-based and allows users to associate a tRF with a universally unique label ('tRF-license plate') that is independent of a genome assembly and does not require any brokering mechanism.

Availability and implementation: MINTbase is freely accessible at http://cm.jefferson.edu/MINTbase/. Dataset submissions to MINTbase can be initiated at http://cm.jefferson.edu/MINTsubmit/

Contact: isidore.rigoutsos@jefferson.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

© The Author 2016. Published by Oxford University Press.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Structural types of tRNA fragments. This is a pictorial summary of the five structural categories of tRNA fragments that are now known to arise from mature tRNAs, both mitochondrially and nuclearly encoded ones
Fig. 2.
Fig. 2.
Search form of MINTbase. The user can select one of the five possible vistas then impose specific search criteria through specific selections and the available filters. The user can optionally work with only tRFs for which there is evidence of expression in the literature or with all tRFs that can potentially arise from a mature tRNA. Filters can include one or more of the structural types of a fragment, amino acid and anticodon, tRNA name, tRF nucleotide sequence, tRF name, chromosome, strand, etc
Fig. 3.
Fig. 3.
Genomic loci vista. The output of this vista presents the user with information about the tRF type, the tRF’s nucleotide sequence, the corresponding amino acid and anticodon identity, the tRF's genomic coordinates (global) and the tRF’s coordinates within the parental tRNA (local). Also included is information on whether a fragment has been reported as expressed in the literature. The results are organized as a table. Menu bars above and below the table enable navigation in multi-page outputs and also give the user the ability to interact with the presented output: columns can be shown/hidden at will, the number of results shown per page can be modified and the generated results downloaded. The headers of several columns are interactive and allow the user to sort the corresponding column’s contents; a second click on a column’s header reverses the sorting order. Holding down the ‘shift’ key and clicking on multiple headers, allows for multi-sorting of the corresponding columns (in the order the headers were selected by the user). The sequence, expression and tRNA alignment columns provide links to the other four vistas of MINTbase
Fig. 4.
Fig. 4.
RNA molecule vista. The output of this vista presents the user with fragment level information. The results are again organized as a table with menu bars above and below the table enabling navigation and user-interaction with the data (see also text and caption of Fig. 3). As in the Genomic Loci vista, the column headers are interactive and permit single-column and multi-column sorting. The nucleotide sequence column links to the ‘Summary’ vista, the column listing the number of genomic loci links to the ‘Genomic Loci’ vista, and the expression column links to the ‘Expression’ vista
Fig. 5.
Fig. 5.
tRNA Alignment vista. The output of this vista presents the user with information on how the tRFs relate to the parental tRNA. A counter at the top of the page lists the number of tRFs included on the page. The various tRFs are shown aligned to the parental tRNA, one tRF per line. The parental tRNA’s sequence remains floating as the page is scrolled up/down or right/left. tRFs can be selectively removed from the shown alignment (by clicking on the [×] beside them). Clicking on a fragment’s nucleotide sequence allows the user to transition to the Summary Vista for the corresponding fragment. Clicking on the parental tRNA’s genome-centric label will redirect the user to the UCSC Genome Browser and enable the user to view the tRNA in its genomic context. Clicking on ‘Undo,’ restores the output to its original version. Different colors indicate the location of relevant information such as D-loop, anticodon, T-loop, intron (if appropriate), etc. A legend at the top of the page describes the used color-coding
Fig. 6.
Fig. 6.
Expression vista. The above is an instance of the detailed tRF-centric layer of this vista. For the user-selected fragment, the user is presented with information about the tRF’s expression across the MINTbase datasets in which it is expressed. Menu bars above and below the table enable navigation and user-interaction with the presented data. Columns can be hidden at will, the number of results shown per page can be modified, and the generated results downloaded. The table’s headers are interactive and allow the user to sort the columns’ contents. In the above example, only a few of the many possible columns are shown (‘unhidden’)
Fig. 7.
Fig. 7.
tRF summary vista. The output of this vista presents basic information about each tRF that is in MINTbase. It includes the tRF’s license plate (the unique sequence-centric identifier introduced by MINTbase—see text), a list of genome-centric labels as discussed in the text, the number of the tRF’s genomic instances, its structural type, whether the tRF appears only inside the tRNA space, a list of all possible parental tRNAs with the tRF underlined in each and the number of datasets currently in MINTbase in which the tRF is expressed
See this image and copyright information in PMC

References

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