Synergistic drug combination prediction by integrating multiomics data in deep learning models

Tianyu Zhang, Liwei Zhang, Philip R.O. Payne, Fuhai Li

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Intrinsic and acquired drug resistance is a major challenge in cancer therapy. Synergistic drug combinations could help to overcome drug resistance. However, the number of possible drug combinations is enormous, and it is infeasible to experimentally screen all drug combinations with limited resources. Therefore, computational models to predict and prioritize effective drug combinations are important for combination therapy discovery. Compared with existing models, we propose a novel deep learning model, AuDNNsynergy, to predict the synergy of pairwise drug combinations by integrating multiomics data. Specifically, three autoencoders are trained using the gene expression, copy number, and genetic mutation data of tumor samples from The Cancer Genome Atlas (TCGA). Then the gene expression, copy number, and mutation of individual cancer cell lines are coded using the three trained autoencoders. The physicochemical features of individual drugs and the encoded omics data of individual cancer cell lines are used as the input features of a deep neural network that predicts the synergy score of given pairwise drug combinations against the specific cancer cell lines. The comparison results showed the proposed AuDNNsynergy model outperforms, specifically in terms of rank correlation metric, four state-of-the-art approaches, namely, DeepSynergy, Gradient Boosting Machines, Random Forests, and Elastic Nets.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press
Pages223-238
Number of pages16
Volume2194
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2194
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Deep learning models
  • Multiomics
  • Prediction methods

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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  • Cite this

    Zhang, T., Zhang, L., Payne, P. R. O., & Li, F. (2021). Synergistic drug combination prediction by integrating multiomics data in deep learning models. In Methods in Molecular Biology (Vol. 2194, pp. 223-238). (Methods in Molecular Biology; Vol. 2194). Humana Press. https://doi.org/10.1007/978-1-0716-0849-4_12