Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression
Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression
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DOI：
10.1371/journal.pcbi.1006453
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发表时间：
2019-09-01
影响因子：
4.3
通讯作者：
Nixon, Douglas F.
中科院分区：
文献类型：
--
作者：
Bendall, Matthew L.;de Mulder, Miguel;Nixon, Douglas F.
由于序列相似性，使用RNA-seq在转录组景观中表征人内源性逆转录病毒（HERV）表达由于片段分配的不确定性而变得复杂。我们提出望远镜，一个计算软件工具，提供准确的估计转座因子表达（逆转录组）解决特定的基因组位置。Telescope通过将模糊映射的片段重新分配给贝叶斯统计模型中确定的最可能的源转录本，直接解决了片段分配中的不确定性。我们通过对13种ENCODE细胞类型中HERV表达的单位点分析证明了我们方法的实用性。当在这个分辨率下检查时，我们发现逆转录组的大小和宽度在细胞类型之间可能有很大的不同。此外，我们的方法对测序技术的差异具有鲁棒性，并证明逆转录组具有用于细胞类型鉴定的潜力。我们将我们的工具与其他量化TE表达的方法进行了比较，发现Telescope具有最高的分辨率，因为它估计了特定TE插入而不是TE亚家族水平的表达。Telescope在RNA-seq实验中对逆转录组学景观进行了高度准确的定量，揭示了以前未观察到的复杂系统的转座因子生物学中的差异复杂性。望远镜可在https://github.com/mlbendall/telescope上获得。
Characterization of Human Endogenous Retrovirus (HERV) expression within the transcriptomic landscape using RNA-seq is complicated by uncertainty in fragment assignment because of sequence similarity. We present Telescope, a computational software tool that provides accurate estimation of transposable element expression (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We demonstrate the utility of our approach through single locus analysis of HERV expression in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude and breadth of the retrotranscriptome can be vastly different among cell types. Furthermore, our approach is robust to differences in sequencing technology, and demonstrates that the retrotranscriptome has potential to be used for cell type identification. We compared our tool with other approaches for quantifying TE expression, and found that Telescope has the greatest resolution, as it estimates expression at specific TE insertions rather than at the TE subfamily level. Telescope performs highly accurate quantification of the retrotranscriptomic landscape in RNA-seq experiments, revealing a differential complexity in the transposable element biology of complex systems not previously observed. Telescope is available at https://github.com/mlbendall/telescope.