PathCNN: interpretable convolutional neural networks for survival prediction and pathway analysis applied to glioblastoma

MOTIVATION: Convolutional neural networks (CNNs) have achieved great success in the areas of image processing and computer vision, handling grid-structured inputs and efficiently capturing local dependencies through multiple levels of abstraction. However, a lack of interpretability remains a key barrier to the adoption of deep neural networks, particularly in predictive modeling of disease outcomes. Moreover, because biological array data are generally represented in a non-grid structured format, CNNs cannot be applied directly. RESULTS: To address these issues, we propose a novel method, called PathCNN, that constructs an interpretable CNN model on integrated multi-omics data using a newly defined pathway image. PathCNN showed promising predictive performance in differentiating between long-term survival (LTS) and non-LTS when applied to glioblastoma multiforme (GBM). The adoption of a visualization tool coupled with statistical analysis enabled the identification of plausible pathways associated with survival in GBM. In summary, PathCNN demonstrates that CNNs can be effectively applied to multi-omics data in an interpretable manner, resulting in promising predictive power while identifying key biological correlates of disease. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at: https://github.com/mskspi/PathCNN.