GenNet framework: interpretable deep learning for predicting phenotypes from genetic data.

Journal: Communications biology
Published Date:

Abstract

Applying deep learning in population genomics is challenging because of computational issues and lack of interpretable models. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this framework, interpretable and memory-efficient neural network architectures are constructed by embedding biologically knowledge from public databases, resulting in neural networks that contain only biologically plausible connections. We applied the framework to seventeen phenotypes and found well-replicated genes such as HERC2 and OCA2 for hair and eye color, and novel genes such as ZNF773 and PCNT for schizophrenia. Additionally, the framework identified ubiquitin mediated proteolysis, endocrine system and viral infectious diseases as most predictive biological pathways for schizophrenia. GenNet is a freely available, end-to-end deep learning framework that allows researchers to develop and use interpretable neural networks to obtain novel insights into the genetic architecture of complex traits and diseases.

Authors

  • Arno van Hilten
    Department of Radiology and Nuclear Medicine, Erasmus MC, Medical Center, Rotterdam, the Netherlands. a.vanhilten@erasmusmc.nl.
  • Steven A Kushner
    Department of Psychiatry, Erasmus MC, Medical Center, Rotterdam, the Netherlands.
  • Manfred Kayser
    Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: m.kayser@erasmusmc.nl.
  • M Arfan Ikram
  • Hieab H H Adams
    Department of Radiology and Nuclear Medicine, Erasmus MC, Medical Center, Rotterdam, the Netherlands.
  • Caroline C W Klaver
    Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands; Institute for Molecular and Clinical Ophthalmology, Basel, Switzerland.
  • Wiro J Niessen
    Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Gennady V Roshchupkin
    Department of Radiology and Nuclear Medicine, Erasmus MC, Medical Center, Rotterdam, the Netherlands. g.roshchupkin@erasmusmc.nl.