Xiao Zhengtao, Zou Qin, Liu Yu, Yang Xuerui
MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Joint Center for Life Sciences, Beijing 100084, China.
Nat Commun. 2016 Apr 4;7:11194. doi: 10.1038/ncomms11194.
The closely regulated process of mRNA translation is crucial for precise control of protein abundance and quality. Ribosome profiling, a combination of ribosome foot-printing and RNA deep sequencing, has been used in a large variety of studies to quantify genome-wide mRNA translation. Here, we developed Xtail, an analysis pipeline tailored for ribosome profiling data that comprehensively and accurately identifies differentially translated genes in pairwise comparisons. Applied on simulated and real datasets, Xtail exhibits high sensitivity with minimal false-positive rates, outperforming existing methods in the accuracy of quantifying differential translations. With published ribosome profiling datasets, Xtail does not only reveal differentially translated genes that make biological sense, but also uncovers new events of differential translation in human cancer cells on mTOR signalling perturbation and in human primary macrophages on interferon gamma (IFN-γ) treatment. This demonstrates the value of Xtail in providing novel insights into the molecular mechanisms that involve translational dysregulations.
mRNA翻译的严格调控过程对于精确控制蛋白质丰度和质量至关重要。核糖体谱分析，即核糖体足迹法与RNA深度测序的结合，已在大量研究中用于全基因组范围内mRNA翻译的定量分析。在此，我们开发了Xtail，这是一种专门针对核糖体谱分析数据的分析流程，可在成对比较中全面、准确地识别差异翻译基因。应用于模拟和真实数据集时，Xtail具有高灵敏度和极低的假阳性率，在定量差异翻译的准确性方面优于现有方法。利用已发表的核糖体谱分析数据集，Xtail不仅揭示了具有生物学意义的差异翻译基因，还发现了人类癌细胞在mTOR信号扰动时以及人类原代巨噬细胞在干扰素γ（IFN-γ）处理时新的差异翻译事件。这证明了Xtail在深入了解涉及翻译失调的分子机制方面的价值。
