Effective integration of multi-omics with prior knowledge to identify biomarkers via explainable graph neural networks.

Journal: NPJ systems biology and applications
PMID:

Abstract

The rapid growth of multi-omics datasets and the wealth of biological knowledge necessitates the development of effective methods for their integration. Such methods are essential for building predictive models and identifying drug targets based on a limited number of samples. We propose a framework called GNNRAI for the supervised integration of multi-omics data with biological priors represented as knowledge graphs. Our framework leverages graph neural networks (GNNs) to model the correlation structures among features from high-dimensional 'omics data, which reduces the effective dimensions in data and enables us to analyze thousands of genes simultaneously using hundreds of samples. Furthermore, our framework incorporates explainability methods to elucidate informative biomarkers. We apply our framework to Alzheimer's disease (AD) multi-omics data, showing that the integration of transcriptomics and proteomics data with prior AD knowledge is effective, improving the prediction accuracy of AD status over single-omics analyses and highlighting both known and novel AD-predictive biomarkers.

Authors

  • Rohit K Tripathy
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Zachary Frohock
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Hong Wang
    Department of Cardiology, Liuzhou Workers' Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.
  • Gregory A Cary
    The Jackson Laboratory, Bar Harbor, ME, USA.
  • Stephen Keegan
    The Jackson Laboratory, Bar Harbor, ME, USA.
  • Gregory W Carter
    The Jackson Laboratory, Bar Harbor, ME, USA. Gregory.Carter@jax.org.
  • Yi Li
    Wuhan Zoncare Bio-Medical Electronics Co., Ltd, Wuhan, China.