Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming
Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming
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DOI：
10.1038/s41598-019-42348-x
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发表时间：
2019-04-18
影响因子：
4.6
通讯作者：
O'Brien, Edward P.
中科院分区：
文献类型：
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作者：
Ahmed, Nabeel;Sormanni, Pietro;O'Brien, Edward P.
从Ribo-Seq实验中识别核糖体保护的mRNA片段上的A-和P-位点位置是在密码子水平上定量分析转录组范围翻译特性的基本步骤。Ribo-Seq数据的许多分析已经利用应用于窄范围的片段大小的启发式方法来鉴定A位点。在这项研究中，我们使用的目标函数最大化，反映了核糖体的核糖体保护片段上的A-位点必须驻留在第二和终止密码子的mRNA之间的事实，使用的编程来确定A-网站。这将A位点位置鉴定为片段大小及其在从S产生的Ribo-Seq数据中的5'端阅读框的函数。酿酒酵母和小鼠胚胎干细胞。所确定的A-位点的位置的正确性表明，这种方法，与其他相比，产生最大的核糖体密度在建立失速位点。通过提供更高的准确性和更宽范围的片段大小的利用，我们的方法增加了与密码子长度尺度上的翻译延伸相关的潜在生物信号的信噪比。
Identifying the A- and P-site locations on ribosome-protected mRNA fragments from Ribo-Seq experiments is a fundamental step in the quantitative analysis of transcriptome-wide translation properties at the codon level. Many analyses of Ribo-Seq data have utilized heuristic approaches applied to a narrow range of fragment sizes to identify the A-site. In this study, we use Integer Programming to identify the A-site by maximizing an objective function that reflects the fact that the ribosome's A-site on ribosome-protected fragments must reside between the second and stop codons of an mRNA. This identifies the A-site location as a function of the fragment's size and its 5' end reading frame in Ribo-Seq data generated from S. cerevisiae and mouse embryonic stem cells. The correctness of the identified A-site locations is demonstrated by showing that this method, as compared to others, yields the largest ribosome density at established stalling sites. By providing greater accuracy and utilization of a wider range of fragment sizes, our approach increases the signal-to-noise ratio of underlying biological signals associated with translation elongation at the codon length scale.