TAPAS: tool for alternative polyadenylation site analysis
TAPAS: tool for alternative polyadenylation site analysis
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TAPAS：替代聚腺苷酸化位点分析工具
DOI：
10.1093/bioinformatics/bty110
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发表时间：
2018-08-01
期刊：
影响因子：
5.8
通讯作者：
Jiang, Tao
中科院分区：
文献类型：
--
作者：
Arefeen, Ashraful;Liu, Juntao;Jiang, Tao
mRNA的3‘非翻译区（3’ UTR）长度对mRNA的稳定性、亚细胞定位、蛋白质翻译、蛋白质结合和翻译效率等许多生物活性至关重要。此外，已有文献报道疾病与3' utr缩短（或延长）之间的相关性。这个长度很大程度上是由mRNA中的聚腺苷化切割位点决定的。由于选择性多聚腺苷化（APA）位点在哺乳动物基因中很常见，最近已经发表了一些工具，用于从RNA-Seq数据中检测APA位点或进行缩短/延长分析。尽管一个基因通常可能有两个以上的APA位点，而且APA位点有时可能出现在最后一个外显子之前，但这些工具要么考虑基因中最多只有两个APA位点，要么只考虑APA位点出现在基因的最后一个外显子上。此外，这些工具无法将缩短/延长事件的分析与APA位点检测相结合。结果：我们提出了一种名为TAPAS的新工具，用于从RNA-Seq数据中检测新的APA位点。它可以处理一个基因中两个以上的APA位点以及发生在最后一个外显子之前的APA位点。该工具是基于现有的方法来查找时间序列数据中的变化点，但也采用了一些过滤技术来去除可能是错误APA位点的变化点。然后将其扩展到鉴定在两个生物样品和含有缩短/延长事件的3' utr的基因之间表达不同的APA位点。我们对模拟和真实RNA-Seq数据的大量实验表明，TAPAS显著优于现有的APA位点检测或缩短/延长分析工具。
Motivation: The length of the 3' untranslated region (3' UTR) of an mRNA is essential for many biological activities such as mRNA stability, sub-cellular localization, protein translation, protein binding and translation efficiency. Moreover, correlation between diseases and the shortening (or lengthening) of 3' UTRs has been reported in the literature. This length is largely determined by the polyadenylation cleavage site in the mRNA. As alternative polyadenylation (APA) sites are common in mammalian genes, several tools have been published recently for detecting APA sites from RNA-Seq data or performing shortening/lengthening analysis. These tools consider either up to only two APA sites in a gene or only APA sites that occur in the last exon of a gene, although a gene may generally have more than two APA sites and an APA site may sometimes occur before the last exon. Furthermore, the tools are unable to integrate the analysis of shortening/lengthening events with APA site detection.Results: We propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data. It can deal with more than two APA sites in a gene as well as APA sites that occur before the last exon. The tool is based on an existing method for finding change points in time series data, but some filtration techniques are also adopted to remove change points that are likely false APA sites. It is then extended to identify APA sites that are expressed differently between two biological samples and genes that contain 3' UTRs with shortening/lengthening events. Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.