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基于潜在空间的多种异质网络表示用于合成致死性预测。

Multiple Heterogeneous Networks Representation With Latent Space for Synthetic Lethality Prediction.

出版信息

IEEE Trans Nanobioscience. 2024 Oct;23(4):564-571. doi: 10.1109/TNB.2024.3444922. Epub 2024 Oct 15.

Abstract

Computational synthetic lethality (SL) method has become a promising strategy to identify SL gene pairs for targeted cancer therapy and cancer medicine development. Feature representation for integrating various biological networks is crutial to improve the identification performance. However, previous feature representation, such as matrix factorization and graph neural network, projects gene features onto latent variables by keeping a specific geometric metric. There is a lack of models of gene representational latent space with considerating multiple dimentionalities correlation and preserving latent geometric structures in both sample and feature spaces. Therefore, we propose a novel method to model gene Latent Space using matrix Tri-Factorization (LSTF) to obtain gene representation with embedding variables resulting from the potential interpretation of synthetic lethality. Meanwhile, manifold subspace regularization is applied to the tri-factorization to capture the geometrical manifold structure in the latent space with gene PPI functional and GO semantic embeddings. Then, SL gene pairs are identified by the reconstruction of the associations with gene representations in the latent space. The experimental results illustrate that LSTF is superior to other state-of-the-art methods. Case study demonstrate the effectiveness of the predicted SL associations.

摘要

计算合成致死(SL)方法已成为一种有前途的策略,可用于鉴定靶向癌症治疗和癌症药物开发的 SL 基因对。整合各种生物网络的特征表示对于提高识别性能至关重要。然而,以前的特征表示方法,如矩阵分解和图神经网络,通过保持特定的几何度量将基因特征投影到潜在变量上。缺乏考虑多个维度相关性并保留样本和特征空间中潜在几何结构的基因表示潜在空间模型。因此,我们提出了一种使用矩阵三因子分解(LSTF)来建模基因潜在空间的新方法,以获得具有潜在合成致死解释的嵌入变量的基因表示。同时,流形子空间正则化应用于三因子分解,以捕获潜在空间中的几何流形结构,该结构与基因 PPI 功能和 GO 语义嵌入相关。然后,通过在潜在空间中使用基因表示对关联进行重建来识别 SL 基因对。实验结果表明,LSTF 优于其他最先进的方法。案例研究证明了预测的 SL 关联的有效性。

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