Zhang Ge, Chen Yitong, Yan Chaokun, Wang Jianlin, Liang Wenjuan, Luo Junwei, Luo Huimin
School of Computer and Information Engineering, Henan University, Kaifeng, Henan, China.
Henan Key Laboratory of Big Data Analysis and Processing, Henan University, Kaifeng, Henan, China.
Front Pharmacol. 2024 May 21;15:1398231. doi: 10.3389/fphar.2024.1398231. eCollection 2024.
Synthetic lethality (SL) is widely used to discover the anti-cancer drug targets. However, the identification of SL interactions through wet experiments is costly and inefficient. Hence, the development of efficient and high-accuracy computational methods for SL interactions prediction is of great significance. In this study, we propose MPASL, a multi-perspective learning knowledge graph attention network to enhance synthetic lethality prediction. MPASL utilizes knowledge graph hierarchy propagation to explore multi-source neighbor nodes related to genes. The knowledge graph ripple propagation expands gene representations through existing gene SL preference sets. MPASL can learn the gene representations from both gene-entity perspective and entity-entity perspective. Specifically, based on the aggregation method, we learn to obtain gene-oriented entity embeddings. Then, the gene representations are refined by comparing the various layer-wise neighborhood features of entities using the discrepancy contrastive technique. Finally, the learned gene representation is applied in SL prediction. Experimental results demonstrated that MPASL outperforms several state-of-the-art methods. Additionally, case studies have validated the effectiveness of MPASL in identifying SL interactions between genes.
合成致死(SL)被广泛用于发现抗癌药物靶点。然而,通过湿实验鉴定SL相互作用成本高且效率低。因此,开发高效、高精度的计算方法来预测SL相互作用具有重要意义。在本研究中,我们提出了MPASL,一种多视角学习知识图谱注意力网络,以增强合成致死预测。MPASL利用知识图谱层次传播来探索与基因相关的多源邻居节点。知识图谱涟漪传播通过现有的基因SL偏好集扩展基因表示。MPASL可以从基因-实体视角和实体-实体视角学习基因表示。具体来说,基于聚合方法,我们学习获得面向基因的实体嵌入。然后,使用差异对比技术通过比较实体的各层邻域特征来细化基因表示。最后,将学习到的基因表示应用于SL预测。实验结果表明,MPASL优于几种现有最先进的方法。此外,案例研究验证了MPASL在识别基因间SL相互作用方面的有效性。