Detecting translational regulation by change point analysis of ribosome profiling data sets.
Detecting translational regulation by change point analysis of ribosome profiling data sets.
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DOI：
10.1261/rna.045286.114
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Shanley DP
中科院分区：
文献类型：
--
作者：
Zupanic A;Meplan C;Grellscheid SN;Mathers JC;Kirkwood TB;Hesketh JE;Shanley DP
Ribo-Seq绘制成熟mRNA转录物上翻译核糖体的位置。而在正常翻译过程中，核糖体密度沿着mRNA编码区长度是恒定的，这可以在响应翻译调控事件时改变。在本研究中，我们开发了一种方法，利用核糖体密度的变化，从单个mrna的核糖体谱中检测其翻译调节。我们使用数学模型来显示核糖体密度的变化应该发生在mRNA的调控点。我们分析了小鼠胚胎干细胞的核糖核酸序列数据集，发现通过相应rna序列的归一化可以通过消除深度测序和比对伪影带来的偏差来提高核糖核酸序列的质量。归一化后，我们应用变化点算法来检测单个mRNA核糖体谱中存在的核糖体密度的变化。从UCSC基因组浏览器获得的其他序列和基因异构体信息使我们能够进一步将检测到的变化分类为不同的调节机制。特别是，我们检测到一些已知的mrna具有转录后调控，例如硒蛋白mrna的过早终止和Atf4的翻译控制，但还有一些mrna具有迄今未知的翻译调控。此外，我们的方法被证明对鉴定新的转录异构体是有用的。
Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosome density is constant along the length of the mRNA coding region, this can be altered in response to translational regulatory events. In the present study, we developed a method to detect translational regulation of individual mRNAs from their ribosome profiles, utilizing changes in ribosome density. We used mathematical modeling to show that changes in ribosome density should occur along the mRNA at the point of regulation. We analyzed a Ribo-Seq data set obtained for mouse embryonic stem cells and showed that normalization by corresponding RNA-Seq can be used to improve the Ribo-Seq quality by removing bias introduced by deep-sequencing and alignment artifacts. After normalization, we applied a change point algorithm to detect changes in ribosome density present in individual mRNA ribosome profiles. Additional sequence and gene isoform information obtained from the UCSC Genome Browser allowed us to further categorize the detected changes into different mechanisms of regulation. In particular, we detected several mRNAs with known post-transcriptional regulation, e.g., premature termination for selenoprotein mRNAs and translational control of Atf4, but also several more mRNAs with hitherto unknown translational regulation. Additionally, our approach proved useful for identification of new transcript isoforms.
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DOI：
10.1083/jcb.108.2.229
发表时间：
1989-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
DOI：
10.1088/0305-4470/36/8/302
发表时间：
2003-02-28
期刊：
JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL
影响因子：
--
作者：
Lakatos, G;Chou, T
通讯作者：
Chou, T
影响因子：
4.8
作者：
Howard, Michael T.;Carlson, Bradley A.;Hatfield, Dolph L.
通讯作者：
Hatfield, Dolph L.
影响因子：
14.9
作者：
Hansen KD;Brenner SE;Dudoit S
通讯作者：
Dudoit S
DOI：
10.1073/pnas.1207846109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Lee, Sooncheol;Liu, Botao;Qian, Shu-Bing
通讯作者：
Qian, Shu-Bing