Unveiling new disease, pathway, and gene associations via multi-scale neural network

PLoS One. 2020 Apr 6;15(4):e0231059. doi: 10.1371/journal.pone.0231059. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comorbidity
  • Computational Biology / methods*
  • Disease / genetics*
  • Gene Regulatory Networks*
  • Humans
  • Models, Biological
  • Neural Networks, Computer*
  • Prognosis
  • ROC Curve
  • Signal Transduction / genetics
  • Transcriptome*

Grants and funding

This work was supported by the European Research Council (ERC) Consolidator Grant 770827, UCL Computer Science, the Slovenian Research Agency project J1-8155, the Serbian Ministry of Education and Science Project III44006, the Prostate Project, the Fondation Toulouse Cancer Sante and Pierre Fabre Research Institute as part of the Chair of Bio-Informatics in Oncology of the CRCT, PhD Fellowship (BES-2016-077403) and the Spanish Ministry of Economics and Competitiveness (BFU2015-71241-R)