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IsoMiRmap:从短RNA测序数据集中快速、确定性且详尽地挖掘异构体微小RNA

IsoMiRmap: fast, deterministic and exhaustive mining of isomiRs from short RNA-seq datasets.

作者信息

Loher Phillipe, Karathanasis Nestoras, Londin Eric, F Bray Paul, Pliatsika Venetia, Telonis Aristeidis G, Rigoutsos Isidore

机构信息

Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA.

出版信息

Bioinformatics. 2021 Jul 27;37(13):1828-1838. doi: 10.1093/bioinformatics/btab016.

Abstract

MOTIVATION

MicroRNA (miRNA) precursor arms give rise to multiple isoforms simultaneously called 'isomiRs.' IsomiRs from the same arm typically differ by a few nucleotides at either their 5' or 3' termini or both. In humans, the identities and abundances of isomiRs depend on a person's sex and genetic ancestry as well as on tissue type, tissue state and disease type/subtype. Moreover, nearly half of the time the most abundant isomiR differs from the miRNA sequence found in public databases. Accurate mining of isomiRs from deep sequencing data is thus important.

RESULTS

We developed isoMiRmap, a fast, standalone, user-friendly mining tool that identifies and quantifies all isomiRs by directly processing short RNA-seq datasets. IsoMiRmap is a portable 'plug-and-play' tool, requires minimal setup, has modest computing and storage requirements, and can process an RNA-seq dataset with 50 million reads in just a few minutes on an average laptop. IsoMiRmap deterministically and exhaustively reports all isomiRs in a given deep sequencing dataset and quantifies them accurately (no double-counting). IsoMiRmap comprehensively reports all miRNA precursor locations from which an isomiR may be transcribed, tags as 'ambiguous' isomiRs whose sequences exist both inside and outside of the space of known miRNA sequences and reports the public identifiers of common single-nucleotide polymorphisms and documented somatic mutations that may be present in an isomiR. IsoMiRmap also identifies isomiRs with 3' non-templated post-transcriptional additions. Compared to similar tools, isoMiRmap is the fastest, reports more bona fide isomiRs, and provides the most comprehensive information related to an isomiR's transcriptional origin.

AVAILABILITY AND IMPLEMENTATION

The codes for isoMiRmap are freely available at https://cm.jefferson.edu/isoMiRmap/ and https://github.com/TJU-CMC-Org/isoMiRmap/. IsomiR profiles for the datasets of the 1000 Genomes Project, spanning five population groups, and The Cancer Genome Atlas (TCGA), spanning 33 cancer studies, are also available at https://cm.jefferson.edu/isoMiRmap/.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

微小RNA(miRNA)前体臂可同时产生多种异构体,称为“异源miR”。来自同一臂的异源miR通常在其5'或3'末端或两端相差几个核苷酸。在人类中,异源miR的身份和丰度取决于一个人的性别、遗传血统以及组织类型、组织状态和疾病类型/亚型。此外,最丰富的异源miR几乎有一半的时间与公共数据库中发现的miRNA序列不同。因此,从深度测序数据中准确挖掘异源miR非常重要。

结果

我们开发了isoMiRmap,这是一种快速、独立、用户友好的挖掘工具,可通过直接处理短RNA测序数据集来识别和量化所有异源miR。isoMiRmap是一种便携式“即插即用”工具,设置要求极低,计算和存储需求适中,在普通笔记本电脑上平均只需几分钟就能处理一个有5000万条读数的RNA测序数据集。isoMiRmap确定性地、详尽地报告给定深度测序数据集中的所有异源miR,并对其进行准确量化(无重复计数)。isoMiRmap全面报告了所有可能转录出异源miR的miRNA前体位置,将那些序列既存在于已知miRNA序列空间内又存在于其外的异源miR标记为“模糊”,并报告可能存在于异源miR中的常见单核苷酸多态性和已记录的体细胞突变的公共标识符。isoMiRmap还能识别具有3'非模板化转录后添加的异源miR。与类似工具相比,isoMiRmap速度最快,报告的真实异源miR更多,并提供了与异源miR转录起源相关的最全面信息。

可用性和实现方式

isoMiRmap的代码可在https://cm.jefferson.edu/isoMiRmap/和https://github.com/TJU-CMC-Org/isoMiRmap/上免费获取。1000基因组计划数据集(涵盖五个群体)和癌症基因组图谱(TCGA,涵盖33项癌症研究)的异源miR图谱也可在https://cm.jefferson.edu/isoMiRmap/上获取。

补充信息

补充数据可在《生物信息学》在线获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bb5/8317110/0287de02d5b1/btab016f1.jpg

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