Department of Biomedical Engineering, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan.
Medical Device Innovation Center, National Cheng Kung University, No.1 University Road, Tainan 701, Taiwan.
J Chem Inf Model. 2024 Apr 8;64(7):2445-2453. doi: 10.1021/acs.jcim.3c01150. Epub 2023 Oct 30.
miRNAs (microRNAs) target specific mRNA (messenger RNA) sites to regulate their translation expression. Although miRNA targeting can rely on seed region base pairing, animal miRNAs, including human miRNAs, typically cooperate with several cofactors, leading to various noncanonical pairing rules. Therefore, identifying the binding sites of animal miRNAs remains challenging. Because experiments for mapping miRNA targets are costly, computational methods are preferred for extracting potential miRNA-mRNA fragment binding pairs first. However, existing prediction tools can have significant false positives due to the prevalent noncanonical miRNA binding behaviors and the information-biased training negative sets that were used while constructing these tools. To overcome these obstacles, we first prepared an information-balanced miRNA binding pair ground-truth data set. A miRNA-mRNA interaction-aware model was then designed to help identify miRNA binding events. On the test set, our model (auROC = 94.4%) outperformed existing models by at least 2.8% in auROC. Furthermore, we showed that this model can suggest potential binding patterns for miRNA-mRNA sequence interacting pairs. Finally, we made the prepared data sets and the designed model available at http://cosbi2.ee.ncku.edu.tw/mirna_binding/download.
miRNAs(microRNAs)靶向特定的 mRNA(信使 RNA)位点来调节其翻译表达。尽管 miRNA 的靶向作用可以依赖于种子区碱基配对,但包括人类 miRNA 在内的动物 miRNA 通常与几个辅助因子合作,导致各种非典型的配对规则。因此,鉴定动物 miRNA 的结合位点仍然具有挑战性。由于 miRNA 靶标定位实验的成本较高,因此,在提取潜在的 miRNA-mRNA 片段结合对时,首选计算方法。然而,由于普遍存在的非典型 miRNA 结合行为以及在构建这些工具时使用的信息偏置训练负集,现有的预测工具可能会有大量的假阳性。为了克服这些障碍,我们首先准备了一个信息平衡的 miRNA 结合对真实数据集。然后设计了一个 miRNA-mRNA 相互作用感知模型来帮助识别 miRNA 结合事件。在测试集上,我们的模型(auROC=94.4%)在 auROC 上比现有模型至少高出 2.8%。此外,我们表明该模型可以为 miRNA-mRNA 序列相互作用对建议潜在的结合模式。最后,我们在 http://cosbi2.ee.ncku.edu.tw/mirna_binding/download 上提供了准备好的数据集和设计好的模型。