Chen Wei, Tang Hua, Ye Jing, Lin Hao, Chou Kuo-Chen
Department of Physics, School of Sciences, and Center for Genomics and Computational Biology, North China University of Science and Technology, Tangshan, China; Gordon Life Science Institute, Boston, Massachusetts, USA.
Department of Pathophysiology, Southwest Medical University, Luzhou, China.
Mol Ther Nucleic Acids. 2016;5(7):e332. doi: 10.1038/mtna.2016.37.
As the most abundant RNA modification, pseudouridine plays important roles in many biological processes. Occurring at the uridine site and catalyzed by pseudouridine synthase, the modification has been observed in nearly all kinds of RNA, including transfer RNA, messenger RNA, small nuclear or nucleolar RNA, and ribosomal RNA. Accordingly, its importance to basic research and drug development is self-evident. Despite some experimental technologies have been developed to detect the pseudouridine sites, they are both time-consuming and expensive. Facing the explosive growth of RNA sequences in the postgenomic age, we are challenged to address the problem by computational approaches: For an uncharacterized RNA sequence, can we predict which of its uridine sites can be modified as pseudouridine and which ones cannot? Here a predictor called "iRNA-PseU" was proposed by incorporating the chemical properties of nucleotides and their occurrence frequency density distributions into the general form of pseudo nucleotide composition (PseKNC). It has been demonstrated via the rigorous jackknife test, independent dataset test, and practical genome-wide analysis that the proposed predictor remarkably outperforms its counterpart. For the convenience of most experimental scientists, the web-server for iRNA-PseU was established at http://lin.uestc.edu.cn/server/iRNA-PseU, by which users can easily get their desired results without the need to go through the mathematical details.
作为最为丰富的RNA修饰,假尿苷在许多生物学过程中发挥着重要作用。这种修饰发生在尿苷位点,由假尿苷合酶催化,几乎在所有类型的RNA中都有观察到,包括转运RNA、信使RNA、小核RNA或核仁RNA以及核糖体RNA。因此,其对基础研究和药物开发的重要性不言而喻。尽管已经开发了一些实验技术来检测假尿苷位点,但这些技术既耗时又昂贵。面对后基因组时代RNA序列的爆炸式增长,我们面临着通过计算方法解决该问题的挑战:对于一个未表征的RNA序列,我们能否预测其哪些尿苷位点可以被修饰为假尿苷,哪些不能?在此,通过将核苷酸的化学性质及其出现频率密度分布纳入伪核苷酸组成(PseKNC)的一般形式,提出了一种名为“iRNA-PseU”的预测器。通过严格的留一法检验、独立数据集检验和实际的全基因组分析证明,所提出的预测器明显优于同类预测器。为方便大多数实验科学家使用,在http://lin.uestc.edu.cn/server/iRNA-PseU上建立了iRNA-PseU的网络服务器,用户通过该服务器可以轻松获得所需结果,而无需了解数学细节。