ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs
ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs
复制标题
DOI：
10.1093/bioinformatics/btab393
复制
发表时间：
2021-05-20
期刊：
影响因子：
5.8
通讯作者：
Davuluri，Ramana
中科院分区：
文献类型：
--
作者：
Chakraborty，Abhijit;Ay，Ferhat;Davuluri，Ramana
对各种组织和细胞系的大规模基因组学和转录组学数据的访问允许在哺乳动物中发现广泛的可选剪接事件和可选启动子的使用。在人类和小鼠之间，目前存在近16k个蛋白质编码基因的基因水平同源性，跨越了超过200k个总转录异构体的不同曲目。在这里，我们描述了一种新的方法，ExTraMapper，它利用一对生物体的外显子之间的序列保守性，并在外显子和转录水平上识别出精细尺度的同源定位。ExTraMapper仅使用序列和基因注释信息就能识别出350,000多个外显子映射，以及人类和小鼠之间的30k个转录本映射。我们证明，与以前的方法相比，ExTraMapper识别了更多的外显子和转录本映射。此外，它还可以识别由于剪接位点突变而导致的外显子融合、分裂和丢失，并发现以前缺失的微外显子之间的映射。通过对来自13个匹配的人和小鼠组织的RNA-seq数据的重新分析，我们发现ExTraMapper提高了转录特异性表达水平的相关性，这表明人类和小鼠转录物的映射更准确。我们还应用该方法检测了人类和恒河猴基因组之间的保守外显子和转录物对，以强调ExTraMapper适用于任何具有同源基因对的生物体。可用性和实施源代码和结果可在https://github.com/ay-lab/ExTraMapper和http://ay-lab-tools.lji.org/extramapper.Supplementary上获得。补充数据可在bioinformatics online上获得。
MotivationAccess to large-scale genomics and transcriptomics data from various tissues and cell lines allowed the discovery of wide-spread alternative splicing events and alternative promoter usage in mammalians. Between human and mouse, gene-level orthology is currently present for nearly 16k protein-coding genes spanning a diverse repertoire of over 200k total transcript isoforms.ResultsHere, we describe a novel method, ExTraMapper, which leverages sequence conservation between exons of a pair of organisms and identifies a fine-scale orthology mapping at the exon and then transcript level. ExTraMapper identifies more than 350k exon mappings, as well as 30k transcript mappings between human and mouse using only sequence and gene annotation information. We demonstrate that ExTraMapper identifies a larger number of exon and transcript mappings compared to previous methods. Further, it identifies exon fusions, splits and losses due to splice site mutations, and finds mappings between microexons that are previously missed. By reanalysis of RNA-seq data from 13 matched human and mouse tissues, we show that ExTraMapper improves the correlation of transcript-specific expression levels suggesting a more accurate mapping of human and mouse transcripts. We also applied the method to detect conserved exon and transcript pairs between human and rhesus macaque genomes to highlight the point that ExTraMapper is applicable to any pair of organisms that have orthologous gene pairs.Availability and implementationThe source code and the results are available at https://github.com/ay-lab/ExTraMapper and http://ay-lab-tools.lji.org/extramapper.Supplementary informationSupplementary data are available atBioinformaticsonline.