RiboProP: a probabilistic ribosome positioning algorithm for ribosome profiling
RiboProP: a probabilistic ribosome positioning algorithm for ribosome profiling
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RiboProP：用于核糖体分析的概率核糖体定位算法
DOI：
10.1093/bioinformatics/bty854
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发表时间：
2018
期刊：
影响因子：
5.8
通讯作者：
Berger, Bonnie
中科院分区：
文献类型：
--
作者：
Zhao, Dengke;Baez, William D;Fredrick, Kurt;Bundschuh, Ralf;Berger, Bonnie
核糖体分析已被广泛用于研究全基因组的翻译。它需要对核糖体保护的mRNA片段进行深度测序，然后将片段映射到参考基因组。对于诸如鉴定核糖体暂停位点之类的应用，仅将片段映射到给定基因是不够的，但必须为每个mRNA片段确定片段所代表的核糖体的确切位置。由于已知的微球菌核酸酶（MNase）序列偏倚导致核糖体保护片段的宽长度分布，使正确核糖体位置的分配变得复杂。微球菌核酸酶是细菌中最广泛使用的核酸酶，用于消化mrna。现有的映射算法在表征核糖体暂停动力学时存在mase偏差或准确性低的问题。结果介绍了一种新的计算方法，将核糖体保护片段定位到核糖体位置。我们首先建立了mase消化和mrna核糖体保护之间相互作用的数学模型。然后，我们使用该模型在每个基因水平上重建核糖体占用谱。我们证明了我们的方法能够减轻由mase引入的序列偏差，并在密码子分辨率上准确定位核糖体暂停位点。我们相信我们的方法可以广泛应用于需要密码子解析的细菌核糖体分析研究。可用性和实现实现我们的方法的源代码可以在http://bioserv.mps.ohio-state.edu/RiboProP.Supplementary的GPL3许可下下载，补充数据可以在bioinformatics online上获得。
MotivationRibosome profiling has been widely used to study translation in a genome-wide fashion. It requires deep sequencing of ribosome protected mRNA fragments followed by mapping of fragments to the reference genome. For applications such as identification of ribosome pausing sites, it is not enough to map a fragment to a given gene, but the exact position of the ribosome represented by the fragment must be identified for each mRNA fragment. The assignment of the correct ribosome position is complicated by the broad length distribution of the ribosome protected fragments caused by the known sequence bias of micrococcal nuclease (MNase), the most widely used nuclease for digesting mRNAs in bacteria. Available mapping algorithms suffer from either MNase bias or low accuracy in characterizing the ribosome pausing kinetics.ResultsIn this paper, we introduce a new computational method for mapping the ribosome protected fragments to ribosome locations. We first develop a mathematical model of the interplay between MNase digestion and ribosome protection of the mRNAs. We then use the model to reconstruct the ribosome occupancy profile on a per gene level. We demonstrate that our method has the capability of mitigating the sequence bias introduced by MNase and accurately locating ribosome pausing sites at codon resolution. We believe that our method can be broadly applied to ribosome profiling studies on bacteria where codon resolution is necessary.Availability and implementationSource code implementing our approach can be downloaded under GPL3 license at http://bioserv.mps.ohio-state.edu/RiboProP.Supplementary informationSupplementary data are available atBioinformaticsonline.
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