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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01196

High-dimensional Bayesian network inference from systems genetics data using genetic node ordering

 Lingfei Wang1, Pieter Audenaert2 and  Tom Michoel1, 3*
  • 1Genetics and Genomics, The Roslin Institute, University of Edinburgh, United Kingdom
  • 2Ghent University, Belgium
  • 3Computational Biology Unit, Department of Informatics, University of Bergen, Norway

Studying the impact of genetic variation on gene regulatory networks is essential to understand the biological mechanisms by which genetic variation causes variation in phenotypes. Bayesian networks provide an elegant statistical approach for multi-trait genetic mapping and modelling causal trait relationships. However, inferring Bayesian gene networks from high-dimensional genetics and genomics data is challenging, because the number of possible networks scales super-exponentially with the number of nodes, and the computational cost of conventional Bayesian network inference methods quickly becomes prohibitive. We propose an alternative method to infer high-quality Bayesian gene networks that easily scales to thousands of genes. Our method first reconstructs a node ordering by conducting pairwise causal inference tests between genes, which then allows to infer a Bayesian network via a series of independent variable selection problems, one for each gene. We demonstrate using simulated and real systems genetics data that this results in a Bayesian network with equal, and sometimes better, likelihood than the conventional methods, while having a significantly higher overlap with groundtruth networks and being orders of magnitude faster. Moreover our method allows for a unified false discovery rate control across genes and individual edges, and thus a rigorous and easily interpretable way for tuning the sparsity level of the inferred network. Bayesian network inference using pairwise node ordering is a highly efficient approach for reconstructing gene regulatory networks when prior information for the inclusion of edges exists or can be inferred from the available data.

Keywords: Systems genetics, Network Inference, Bayesian network, eQTL analysis, Gene expresion

Received: 03 Jul 2019; Accepted: 29 Oct 2019.

Copyright: © 2019 Wang, Audenaert and Michoel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Tom Michoel, University of Bergen, Computational Biology Unit, Department of Informatics, Bergen, Norway, tom.michoel@uib.no