Integrating multi-omics data by learning modality invariant representations for improved prediction of overall survival of cancer.

Abstract

Breast and ovarian cancers are the second and the fifth leading causes of cancer death among women. Predicting the overall survival of breast and ovarian cancer patients can facilitate the therapeutics evaluation and treatment decision making. Multi-scale multi-omics data such as gene expression, DNA methylation, miRNA expression, and copy number variations can provide insights on personalized survival. However, how to effectively integrate multi-omics data remains a challenging task. In this paper, we develop multi-omics integration methods to improve the prediction of overall survival for breast cancer and ovarian cancer patients. Because multi-omics data for the same patient jointly impact the survival of cancer patients, features from different -omics modality are related and can be modeled by either association or causal relationship (e.g., pathways). By extracting these relationships among modalities, we can get rid of the irrelevant information from high-throughput multi-omics data. However, it is infeasible to use the Brute Force method to capture all possible multi-omics interactions. Thus, we use deep neural networks with novel divergence-based consensus regularization to capture multi-omics interactions implicitly by extracting modality-invariant representations. In comparing the concatenation-based integration networks with our new divergence-based consensus networks, the breast cancer overall survival C-index is improved from 0.655±0.062 to 0.671±0.046 when combing DNA methylation and miRNA expression, and from 0.627±0.062 to 0.667±0.073 when combing miRNA expression and copy number variations. In summary, our novel deep consensus neural network has successfully improved the prediction of overall survival for breast cancer and ovarian cancer patients by implicitly learning the multi-omics interactions.