IEEE/ACM Trans Comput Biol Bioinform. 2020 May-Jun;17(3):748-757. doi: 10.1109/TCBB.2019.2909908. Epub 2019 Apr 9.
Synthetic lethality (SL) is a promising concept for novel discovery of anti-cancer drug targets. However, wet-lab experiments for detecting SLs are faced with various challenges, such as high cost, low consistency across platforms, or cell lines. Therefore, computational prediction methods are needed to address these issues. This paper proposes a novel SL prediction method, named SL MF, which employs logistic matrix factorization to learn latent representations of genes from the observed SL data. The probability that two genes are likely to form SL is modeled by the linear combination of gene latent vectors. As known SL pairs are more trustworthy than unknown pairs, we design importance weighting schemes to assign higher importance weights for known SL pairs and lower importance weights for unknown pairs in SL MF. Moreover, we also incorporate biological knowledge about genes from protein-protein interaction (PPI) data and Gene Ontology (GO). In particular, we calculate the similarity between genes based on their GO annotations and topological properties in the PPI network. Extensive experiments on the SL interaction data from SynLethDB database have been conducted to demonstrate the effectiveness of SL MF.
合成致死性 (SL) 是一种有前途的新型抗癌药物靶点发现概念。然而,用于检测 SL 的湿实验室实验面临着各种挑战,例如成本高、平台间一致性低或细胞系不同。因此,需要计算预测方法来解决这些问题。本文提出了一种新的 SL 预测方法,称为 SL MF,它使用逻辑矩阵分解从观察到的 SL 数据中学习基因的潜在表示。通过基因潜在向量的线性组合来模拟两个基因形成 SL 的可能性。由于已知的 SL 对比未知的 SL 对更可信,我们设计了重要性加权方案,为 SL MF 中的已知 SL 对分配更高的重要性权重,为未知 SL 对分配更低的重要性权重。此外,我们还结合了来自蛋白质-蛋白质相互作用 (PPI) 数据和基因本体论 (GO) 的基因生物学知识。具体来说,我们根据基因的 GO 注释和 PPI 网络中的拓扑性质计算基因之间的相似性。已经在 SynLethDB 数据库的 SL 相互作用数据上进行了广泛的实验,以证明 SL MF 的有效性。