Multitask Matrix Completion for Learning Protein Interactions Across Diseases

J Comput Biol. 2017 Jun;24(6):501-514. doi: 10.1089/cmb.2016.0201. Epub 2017 Jan 27.

Abstract

Disease-causing pathogens such as viruses introduce their proteins into the host cells in which they interact with the host's proteins, enabling the virus to replicate inside the host. These interactions between pathogen and host proteins are key to understanding infectious diseases. Often multiple diseases involve phylogenetically related or biologically similar pathogens. Here we present a multitask learning method to jointly model interactions between human proteins and three different but related viruses: Hepatitis C, Ebola virus, and Influenza A. Our multitask matrix completion-based model uses a shared low-rank structure in addition to a task-specific sparse structure to incorporate the various interactions. We obtain between 7 and 39 percentage points improvement in predictive performance over prior state-of-the-art models. We show how our model's parameters can be interpreted to reveal both general and specific interaction-relevant characteristics of the viruses. Our code is available online.

Keywords: host–pathogen protein–protein interaction; matrix completion; multitask learning; protein interaction prediction; viruses.

MeSH terms

  • Algorithms*
  • Computational Biology / methods*
  • Databases, Protein
  • Ebolavirus / metabolism
  • Hepacivirus / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Influenza A virus / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Interaction Maps*
  • Proteins / metabolism*

Substances

  • Proteins