Using Deep Learning to Associate Human Genes With Age-Related Diseases

Bioinformatics. 2020 Apr 1;36(7):2202-2208. doi: 10.1093/bioinformatics/btz887.

Abstract

Motivation: One way to identify genes possibly associated with ageing is to build a classification model (from the machine learning field) capable of classifying genes as associated with multiple age-related diseases. To build this model, we use a pre-compiled list of human genes associated with age-related diseases and apply a novel Deep Neural Network (DNN) method to find associations between gene descriptors (e.g. Gene Ontology terms, protein-protein interaction data and biological pathway information) and age-related diseases.

Results: The novelty of our new DNN method is its modular architecture, which has the capability of combining several sources of biological data to predict which ageing-related diseases a gene is associated with (if any). Our DNN method achieves better predictive performance than standard DNN approaches, a Gradient Boosted Tree classifier (a strong baseline method) and a Logistic Regression classifier. Given the DNN model produced by our method, we use two approaches to identify human genes that are not known to be associated with age-related diseases according to our dataset. First, we investigate genes that are close to other disease-associated genes in a complex multi-dimensional feature space learned by the DNN algorithm. Second, using the class label probabilities output by our DNN approach, we identify genes with a high probability of being associated with age-related diseases according to the model. We provide evidence of these putative associations retrieved from the DNN model with literature support.

Availability and implementation: The source code and datasets can be found at: https://github.com/fabiofabris/Bioinfo2019.

Supplementary information: Supplementary data are available at Bioinformatics online.