Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Proteomics and Metabolomics Facility, and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2017 Nov 23;8(1):1749. doi: 10.1038/s41467-017-01981-8.
Translation is principally regulated at the initiation stage. The development of the translation initiation (TI) sequencing (TI-seq) technique has enabled the global mapping of TIs and revealed unanticipated complex translational landscapes in metazoans. Despite the wide adoption of TI-seq, there is no computational tool currently available for analyzing TI-seq data. To fill this gap, we develop a comprehensive toolkit named Ribo-TISH, which allows for detecting and quantitatively comparing TIs across conditions from TI-seq data. Ribo-TISH can also predict novel open reading frames (ORFs) from regular ribosome profiling (rRibo-seq) data and outperform several established methods in both computational efficiency and prediction accuracy. Applied to published TI-seq/rRibo-seq data sets, Ribo-TISH uncovers a novel signature of elevated mitochondrial translation during amino-acid deprivation and predicts novel ORFs in 5'UTRs, long noncoding RNAs, and introns. These successful applications demonstrate the power of Ribo-TISH in extracting biological insights from TI-seq/rRibo-seq data.
翻译主要在起始阶段进行调控。翻译起始（TI）测序（TI-seq）技术的发展使 TI 的全局作图成为可能，并揭示了后生动物中意想不到的复杂翻译景观。尽管 TI-seq 已被广泛采用，但目前还没有用于分析 TI-seq 数据的计算工具。为了填补这一空白，我们开发了一个名为 Ribo-TISH 的综合工具包，该工具包允许从 TI-seq 数据中检测和定量比较不同条件下的 TI。Ribo-TISH 还可以从常规核糖体图谱（rRibo-seq）数据中预测新的开放阅读框（ORF），并且在计算效率和预测准确性方面均优于几种已建立的方法。将 Ribo-TISH 应用于已发表的 TI-seq/rRibo-seq 数据集，揭示了氨基酸剥夺期间线粒体翻译升高的新特征，并预测了 5'UTR、长非编码 RNA 和内含子中的新 ORF。这些成功的应用证明了 Ribo-TISH 从 TI-seq/rRibo-seq 数据中提取生物学见解的强大功能。
