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KLEAT: CLEAVAGE SITE ANALYSIS OF TRANSCRIPTOMES

机译：kleat：转录om的切割位点分析

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摘要

In eukaryotic cells, alternative cleavage of 3'untranslated regions (UTRs) can affect transcript stability, transport and translation. For polyadenylated (poly(A)) transcripts, cleavage sites can be characterized with short-read sequencing using specialized library construction methods. However, for large-scale cohort studies as well as for clinical sequencing applications, it is desirable to characterize such events using RNA-seq data, as the latter are already widely applied to identify other relevant information, such as mutations, alternative splicing and chimeric transcripts. Here we describe KLEAT, an analysis tool that uses de novo assembly of RNA-seq data to characterize cleavage sites on 3' UTRs. We demonstrate the performance of KLEAT on three cell line RNA-seq libraries constructed and sequenced by the ENCODE project, and assembled using Trans-ABySS. Validating the KLEAT predictions with matched ENCODE RNA-seq and RNA-PET libraries, we show that the tool has over 90% positive predictive value when there are at least three RNA-seq reads supporting a poly(A) tail and requiring at least three RNA-PET reads mapping within 100 nucleotides as validation. We also compare the performance of KLEAT with other popular RNA-seq analysis pipelines that reconstruct 3' UTR ends, and show that it performs favourably, based on an ROC-like curve.
机译：在真核细胞中，3'unralstated区（UTRS）的替代切割可以影响转录稳定性，运输和翻译。对于多腺苷酸化（聚（a））转录物，可以使用专用文库施工方法表征裂解位点的短读测序。然而，对于大规模的队列研究以及临床测序应用，希望使用RNA-SEQ数据表征这些事件，因为后者已经广泛应用于识别其他相关信息，例如突变，替代剪接和嵌合转录物。在这里，我们描述了一个使用De Novo集合的RNA-SEQ数据的分析工具，以表征3'UTRS的切割网站。我们展示了KleaT在由编码项目构建和测序的三个细胞系RNA-SEQ库上的性能，并使用跨深度组装。用匹配的编码RNA-SEQ和RNA-PET库验证Kleat预测，我们表明，当存在至少三个RNA-SEQ读取Poly（a）尾部并且需要至少三个时，该工具具有超过90％的阳性预测值。 RNA-PET读取100核苷酸内的映射作为验证。我们还将Kleat与其他流行的RNA-SEQ分析管道进行了比较，该管道重建3'UTR结束，并表明它基于ROC样曲线来表现出有利地执行。

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