Abstract
MOTIVATION: Common human diseases result from the interplay of genes and their biologically associated pathways. Genetic pathway analyses provide more biological insight as compared to conventional gene-based analysis. In this article, we propose a framework combining genetic data into pathway structure and using an ensemble of convolutional neural networks (CNNs) along with a Canonical Correlation Regularizer layer for comprehensive prediction of disease risk. The novelty of our approach lies in our two-step framework: (i) utilizing the CNN's effectiveness to extract the complex gene associations within individual genetic pathways and (ii) fusing features from ensemble of CNNs through Canonical Correlation Regularization layer to incorporate the interactions between pathways which share common genes. During prediction, we also address the important issues of interpretability of neural network models, and identifying the pathways and genes playing an important role in prediction. RESULTS: Implementation of our methodology into three real cancer genetic datasets for different prediction tasks validates our model's generalizability and robustness. Comparing with conventional models, our methodology provides consistently better performance with AUC improvement of 11% on predicting early/late-stage kidney cancer, 10% on predicting kidney versus liver cancer type and 7% on predicting survival status in ovarian cancer as compared to the next best conventional machine learning model. The robust performance of our deep learning algorithm indicates that disease prediction using neural networks in multiple functionally related genes across different pathways improves genetic data-based prediction and understanding molecular mechanisms of diseases. AVAILABILITY AND IMPLEMENTATION: https://github.com/divya031090/ReGeNNe.