Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China.
Bioinformatics. 2020 Aug 1;36(15):4263-4268. doi: 10.1093/bioinformatics/btaa492.
Methylation and transcription factors (TFs) are part of the mechanisms regulating gene expression. However, the numerous mechanisms regulating the interactions between methylation and TFs remain unknown. We employ machine-learning techniques to discover the characteristics of TFs that bind to methylation sites.
The classical machine-learning analysis process focuses on improving the performance of the analysis method. Conversely, we focus on the functional properties of the TF sequences. We obtain the principal properties of TFs, namely, the basic polar and hydrophobic Ile amino acids affecting the interaction between TFs and methylated DNA. The recall of the positive instances is 0.878 when their basic polar value is >0.1743. Both basic polar and hydrophobic Ile amino acids distinguish 74% of TFs bound to methylation sites. Therefore, we infer that basic polar amino acids affect the interactions of TFs with methylation sites. Based on our results, the role of the hydrophobic Ile residue is consistent with that described in previous studies, and the basic polar amino acids may also be a key factor modulating the interactions between TFs and methylation.
Supplementary data are available at Bioinformatics online.
甲基化和转录因子(TFs)是调节基因表达的机制的一部分。然而,调节甲基化和 TFs 之间相互作用的众多机制仍不清楚。我们采用机器学习技术来发现与甲基化位点结合的 TF 的特征。
经典的机器学习分析过程侧重于提高分析方法的性能。相反,我们关注的是 TF 序列的功能特性。我们获得了 TF 的主要特性,即影响 TF 与甲基化 DNA 相互作用的基本极性和疏水性 Ile 氨基酸。当基本极性值大于 0.1743 时,阳性实例的召回率为 0.878。基本极性和疏水性 Ile 氨基酸可区分 74%与甲基化位点结合的 TF。因此,我们推断基本极性氨基酸会影响 TF 与甲基化位点的相互作用。基于我们的结果,疏水性 Ile 残基的作用与先前研究中描述的作用一致,而基本极性氨基酸也可能是调节 TF 与甲基化相互作用的关键因素。
补充数据可在 Bioinformatics 在线获得。