Department of Electronics and Information Engineering, Chonbuk National University, Jeonju 54896, Korea.
Advanced Electronics and Information Research Center, Chonbuk National University, Jeonju 54896, Korea.
Genes (Basel). 2019 Aug 1;10(8):587. doi: 10.3390/genes10080587.
Alternative splicing (AS) is the process of combining different parts of the pre-mRNA to produce diverse transcripts and eventually different protein products from a single gene. In computational biology field, researchers try to understand AS behavior and regulation using computational models known as "Splicing Codes". The final goal of these algorithms is to make an in-silico prediction of AS outcome from genomic sequence. Here, we develop a deep learning approach, called Deep Splicing Code (DSC), for categorizing the well-studied classes of AS namely alternatively skipped exons, alternative 5ss, alternative 3ss, and constitutively spliced exons based only on the sequence of the exon junctions. The proposed approach significantly improves the prediction and the obtained results reveal that constitutive exons have distinguishable local characteristics from alternatively spliced exons. Using the motif visualization technique, we show that the trained models learned to search for competitive alternative splice sites as well as motifs of important splicing factors with high precision. Thus, the proposed approach greatly expands the opportunities to improve alternative splicing modeling. In addition, a web-server for AS events prediction has been developed based on the proposed method and made available at https://home.jbnu.ac.kr/NSCL/dsc.htm.
可变剪接(AS)是指前体 mRNA 结合不同部分产生不同转录本的过程,最终由单个基因产生不同的蛋白质产物。在计算生物学领域,研究人员试图使用称为“剪接代码”的计算模型来理解 AS 行为和调控。这些算法的最终目标是根据基因组序列对 AS 结果进行计算机预测。在这里,我们开发了一种称为深度剪接代码(DSC)的深度学习方法,仅基于外显子连接序列对经过充分研究的 AS 类别进行分类,即选择性跳过外显子、选择性 5ss、选择性 3ss 和组成性剪接外显子。所提出的方法显著提高了预测的准确性,并且所得到的结果表明,组成性外显子与选择性剪接外显子具有可区分的局部特征。通过使用基序可视化技术,我们表明,训练的模型能够高精度地搜索竞争性的替代剪接位点以及重要剪接因子的基序。因此,所提出的方法极大地扩展了改进替代剪接建模的机会。此外,还基于所提出的方法开发了一个用于 AS 事件预测的网络服务器,并可在 https://home.jbnu.ac.kr/NSCL/dsc.htm 上访问。