Gene-centric multi-omics integration with convolutional encoders for cancer drug response prediction.

MOTIVATION

Tumor heterogeneity, including genetic and transcriptomic characteristics, can reduce the efficacy of anticancer pharmacological therapy, resulting in clinical variability in patient response to therapeutic medications. Multi-omics integration can allow in silico models to provide an additional perspective on a biological system.

METHODS

In this study, we propose a gene-centric multi-channel (GCMC) architecture to integrate multi-omics for predicting cancer drug response. GCMC transformed multi-omics profiles into a three-dimensional tensor with an additional dimension for omics types. GCMC's convolutional encoders captures multi-omics profiles for each gene and yields gene-centric features to predict drug responses.

RESULTS

We evaluated GCMC on various datasets, including The Cancer Genome Atlas (TCGA) patients, patient-derived xenografts (PDX) mice models, and the Genomics of Drug Sensitivity in Cancer (GDSC) cell line datasets. GCMC achieved better performance than baseline models, including single-omics models, in more than 75% of 265 drugs from GDSC cell line datasets. Furthermore, as for the clinical applicability of GCMC, it achieved the best performance on TCGA and PDX datasets in terms of both AUPR and AUC. We also analyzed models' capability of integrating multi-omics profiles by measuring the contribution ratio of omics types. GCMC can incorporate multi-omics profiles in various manners to enhance performance for each drug type. These results suggested that GCMC can improve performance and feature extraction capability by integrating multi-omics profiles in a gene-centric manner.