Zhao Bo-Wei, He Yi-Zhou, Su Xiao-Rui, Yang Yue, Li Guo-Dong, Huang Yu-An, Hu Peng-Wei, You Zhu-Hong, Hu Lun
IEEE J Biomed Health Inform. 2024 Jul;28(7):4281-4294. doi: 10.1109/JBHI.2024.3383591. Epub 2024 Jul 2.
As post-transcriptional regulators of gene expression, micro-ribonucleic acids (miRNAs) are regarded as potential biomarkers for a variety of diseases. Hence, the prediction of miRNA-disease associations (MDAs) is of great significance for an in-depth understanding of disease pathogenesis and progression. Existing prediction models are mainly concentrated on incorporating different sources of biological information to perform the MDA prediction task while failing to consider the fully potential utility of MDA network information at the motif-level. To overcome this problem, we propose a novel motif-aware MDA prediction model, namely MotifMDA, by fusing a variety of high- and low-order structural information. In particular, we first design several motifs of interest considering their ability to characterize how miRNAs are associated with diseases through different network structural patterns. Then, MotifMDA adopts a two-layer hierarchical attention to identify novel MDAs. Specifically, the first attention layer learns high-order motif preferences based on their occurrences in the given MDA network, while the second one learns the final embeddings of miRNAs and diseases through coupling high- and low-order preferences. Experimental results on two benchmark datasets have demonstrated the superior performance of MotifMDA over several state-of-the-art prediction models. This strongly indicates that accurate MDA prediction can be achieved by relying solely on MDA network information. Furthermore, our case studies indicate that the incorporation of motif-level structure information allows MotifMDA to discover novel MDAs from different perspectives.
作为基因表达的转录后调节因子,微小核糖核酸(miRNA)被视为多种疾病的潜在生物标志物。因此,预测miRNA与疾病的关联(MDA)对于深入了解疾病的发病机制和进展具有重要意义。现有的预测模型主要集中在整合不同来源的生物信息来执行MDA预测任务,而未能考虑基序水平上MDA网络信息的全部潜在效用。为了克服这个问题,我们通过融合各种高阶和低阶结构信息,提出了一种新颖的基序感知MDA预测模型,即MotifMDA。具体而言,我们首先根据其表征miRNA如何通过不同网络结构模式与疾病相关联的能力,设计了几个感兴趣的基序。然后,MotifMDA采用两层分层注意力来识别新的MDA。具体来说,第一个注意力层根据给定MDA网络中基序的出现情况学习高阶基序偏好,而第二个注意力层通过耦合高阶和低阶偏好来学习miRNA和疾病的最终嵌入。在两个基准数据集上的实验结果表明,MotifMDA优于几种现有最先进的预测模型。这有力地表明,仅依靠MDA网络信息就可以实现准确的MDA预测。此外,我们的案例研究表明,纳入基序水平的结构信息使MotifMDA能够从不同角度发现新的MDA。
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