DBDNMF:用于药物反应预测的双分支深度神经矩阵因式分解方法

IF 4.3 2区 生物学 PLoS Computational Biology Pub Date : 2024-04-01 DOI:10.1371/journal.pcbi.1012012
Hui Liu, Feng Wang, Jian Yu, Yong Pan, Chaoju Gong, Liang Zhang, Lin Zhang
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引用次数: 0

摘要

在精准医疗时代,细胞系对药物的抗癌反应迫切需要个性化的精准医疗决策。湿法实验测量耗时长、成本高,而且几乎不可能广泛应用。设计能精确预测药物与细胞系之间反应的计算模型,可为进一步的研究提供可靠的参考。现有的基于矩阵因式分解或神经网络的反应预测方法表明,线性或非线性潜特征都适用于药物反应的精确预测,且效果显著。然而,大多数方法仅考虑药物反应预测中的线性或非线性关系。在此,我们提出一种双分支深度神经矩阵因式分解(DBDNMF)方法来解决上述问题。DBDNMF 通过灵活的输入学习药物和细胞系的潜在表征,并通过一系列隐藏的神经网络层重建部分观察到的矩阵。在癌症细胞系百科全书(CCLE)和癌症药物敏感性基因组学(GDSC)数据集上的实验结果表明,药物预测的准确性超过了最先进的药物反应预测算法,证明了其可靠性和稳定性。分层聚类结果表明,具有相似反应水平的药物往往针对相似的信号通路,来自相同组织亚型的细胞系往往具有相同的反应模式,这与之前发表的研究结果一致。
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DBDNMF: A Dual Branch Deep Neural Matrix Factorization method for drug response prediction
Anti-cancer response of cell lines to drugs is in urgent need for individualized precision medical decision-making in the era of precision medicine. Measurements with wet-experiments is time-consuming and expensive and it is almost impossible for wide ranges of application. The design of computational models that can precisely predict the responses between drugs and cell lines could provide a credible reference for further research. Existing methods of response prediction based on matrix factorization or neural networks have revealed that both linear or nonlinear latent characteristics are applicable and effective for the precise prediction of drug responses. However, the majority of them consider only linear or nonlinear relationships for drug response prediction. Herein, we propose a Dual Branch Deep Neural Matrix Factorization (DBDNMF) method to address the above-mentioned issues. DBDNMF learns the latent representation of drugs and cell lines through flexible inputs and reconstructs the partially observed matrix through a series of hidden neural network layers. Experimental results on the datasets of Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) show that the accuracy of drug prediction exceeds state-of-the-art drug response prediction algorithms, demonstrating its reliability and stability. The hierarchical clustering results show that drugs with similar response levels tend to target similar signaling pathway, and cell lines coming from the same tissue subtype tend to share the same pattern of response, which are consistent with previously published studies.
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来源期刊
PLoS Computational Biology
PLoS Computational Biology 生物-生化研究方法
CiteScore
7.10
自引率
4.70%
发文量
820
期刊介绍: PLOS Computational Biology features works of exceptional significance that further our understanding of living systems at all scales—from molecules and cells, to patient populations and ecosystems—through the application of computational methods. Readers include life and computational scientists, who can take the important findings presented here to the next level of discovery. Research articles must be declared as belonging to a relevant section. More information about the sections can be found in the submission guidelines. Research articles should model aspects of biological systems, demonstrate both methodological and scientific novelty, and provide profound new biological insights. Generally, reliability and significance of biological discovery through computation should be validated and enriched by experimental studies. Inclusion of experimental validation is not required for publication, but should be referenced where possible. Inclusion of experimental validation of a modest biological discovery through computation does not render a manuscript suitable for PLOS Computational Biology. Research articles specifically designated as Methods papers should describe outstanding methods of exceptional importance that have been shown, or have the promise to provide new biological insights. The method must already be widely adopted, or have the promise of wide adoption by a broad community of users. Enhancements to existing published methods will only be considered if those enhancements bring exceptional new capabilities.
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