Unveiling new disease, pathway, and gene associations via multi-scale neural network
Thomas Gaudelet, Noël Malod‐Dognin, Jon Sánchez-Valle, Véra Pancaldi, Alfonso Valencia, Nataša Pržulj
Abstract
Diseases involve complex modifications to the cellular machinery. The gene expression profile of the affected cells contains characteristic patterns linked to a disease. Hence, new biological knowledge about a disease can be extracted from these profiles, improving our ability to diagnose and assess disease risks. This knowledge can be used for drug re-purposing, or by physicians to evaluate a patient's condition and co-morbidity risk. Here, we consider differential gene expressions obtained by microarray technology for patients diagnosed with various diseases. Based on these data and cellular multi-scale organization, we aim at uncovering disease-disease, disease-gene and disease-pathway associations. We propose a neural network with structure based on the multi-scale organization of proteins in a cell into biological pathways. We show that this model is able to correctly predict the diagnosis for the majority of patients. Through the analysis of the trained model, we predict disease-disease, disease-pathway, and disease-gene associations and validate the predictions by comparisons to known interactions and literature search, proposing putative explanations for the predictions.