IsoSCM: improved and alternative 3' UTR annotation using multiple change-point inference.

IsoSCM: improved and alternative 3' UTR annotation using multiple change-point inference.
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DOI:
10.1261/rna.046037.114
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发表时间:
2015-01
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Lai EC
Lai EC
中科院分区:
其他
文献类型:
--
作者:
Shenker S;Miura P;Sanfilippo P;Lai EC

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RNA-seq数据的主要应用包括研究转录组如何在基因表达和RNA加工水平上被调节,以及这些事件如何与细胞身份、环境条件和/或疾病状态相关。虽然已经开发了许多优秀的工具来分析RNA测序数据,但这些工具对于注释3 'UTR的功效通常有限。现有的组装策略通常会使长的3′ UTR片段化,重要的是,没有一种流行的算法可以将数据分配到串联的3′ UTR异构体中,这些异构体通常通过交替切割和多聚腺苷酸化(阿帕)产生。因此,它往往是不可能的,以确定模式的差异阿帕使用现有的组装工具。为了解决这些局限性,我们提出了一种新的转录本组装方法,异构体结构变化模型(IsoSCM),结合变点分析,以改善3′ UTR注释过程。通过对模拟数据集和真实数据集的评估,我们证明了IsoSCM注释3′末端具有比现有方法更高的灵敏度和特异性。我们强调IsoSCM的效用,证明其恢复已知模式的组织调节阿帕的能力。IsoSCM将促进未来利用RNA-seq数据进行3′ UTR注释和阿帕的广度,调控和作用的全基因组研究。IsoSCM软件和源代码可从我们的网站https://github.com/shenkers/isoscm获得。
Major applications of RNA-seq data include studies of how the transcriptome is modulated at the levels of gene expression and RNA processing, and how these events are related to cellular identity, environmental condition, and/or disease status. While many excellent tools have been developed to analyze RNA-seq data, these generally have limited efficacy for annotating 3′ UTRs. Existing assembly strategies often fragment long 3′ UTRs, and importantly, none of the algorithms in popular use can apportion data into tandem 3′ UTR isoforms, which are frequently generated by alternative cleavage and polyadenylation (APA). Consequently, it is often not possible to identify patterns of differential APA using existing assembly tools. To address these limitations, we present a new method for transcript assembly, Isoform Structural Change Model (IsoSCM) that incorporates change-point analysis to improve the 3′ UTR annotation process. Through evaluation on simulated and genuine data sets, we demonstrate that IsoSCM annotates 3′ termini with higher sensitivity and specificity than can be achieved with existing methods. We highlight the utility of IsoSCM by demonstrating its ability to recover known patterns of tissue-regulated APA. IsoSCM will facilitate future efforts for 3′ UTR annotation and genome-wide studies of the breadth, regulation, and roles of APA leveraging RNA-seq data. The IsoSCM software and source code are available from our website https://github.com/shenkers/isoscm.
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