DBDNMF: A Dual Branch Deep Neural Matrix Factorization method for drug response prediction.

Journal: PLoS computational biology
Published Date:

Abstract

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.

Authors

  • Hui Liu
    Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Feng Wang
    Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
  • Jian Yu
    Key laboratory of Transplantation, Chinese Academy of Medical Sciences, Tianjin, 300192, China; Tianjin Key Laboratory for Organ Transplantation, Tianjin First Center Hospital, Tianjin, 300192, China; Department of Liver Transplantation, Tianjin Medical University First Center Clinical College, Tianjin, 300192, China; Tianjin Key Laboratory of Molecular and Treatment of Liver Cancer, Tianjin First Center Hospital, Tianjin, 300192, China.
  • Yong Pan
    School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, Jiangsu, China.
  • Chaoju Gong
    School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, Jiangsu, China.
  • Liang Zhang
  • Lin Zhang
    Laboratory of Molecular Translational Medicine, Centre for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Clinical Research Center for Birth Defects of Sichuan Province, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: zhanglin@scu.edu.cn.