Exploring the reproducibility of probabilistic causal molecular network models

Ariella Cohain, Aparna A. Divaraniya, Kuixi Zhu, Joseph R. Scarpa, Andrew Kasarskis, Jun Zhu, Rui Chang, Joel T. Dudley, Eric E. Schadt

Research output: Contribution to journalConference articlepeer-review

12 Scopus citations

Abstract

Network reconstruction algorithms are increasingly being employed in biomedical and life sciences research to integrate large-scale, high-dimensional data informing on living systems. One particular class of probabilistic causal networks being applied to model the complexity and causal structure of biological data is Bayesian networks (BNs). BNs provide an elegant mathematical framework for not only inferring causal relationships among many different molecular and higher order phenotypes, but also for incorporating highly diverse priors that provide an efficient path for incorporating existing knowledge. While significant methodological developments have broadly enabled the application of BNs to generate and validate meaningful biological hypotheses, the reproducibility of BNs in this context has not been systematically explored. In this study, we aim to determine the criteria for generating reproducible BNs in the context of transcription-based regulatory networks. We utilize two unique tissues from independent datasets, whole blood from the GTEx Consortium and liver from the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Team (STARNET) study. We evaluated the reproducibility of the BNs by creating networks on data subsampled at different levels from each cohort and comparing these networks to the BNs constructed using the complete data. To help validate our results, we used simulated networks at varying sample sizes. Our study indicates that reproducibility of BNs in biological research is an issue worthy of further consideration, especially in light of the many publications that now employ findings from such constructs without appropriate attention paid to reproducibility. We find that while edge-to-edge reproducibility is strongly dependent on sample size, identification of more highly connected key driver nodes in BNs can be carried out with high confidence across a range of sample sizes.

Original languageEnglish (US)
Pages (from-to)120-131
Number of pages12
JournalPacific Symposium on Biocomputing
Volume0
Issue number212679
DOIs
StatePublished - 2017
Externally publishedYes
Event22nd Pacific Symposium on Biocomputing, PSB 2017 - Kohala Coast, United States
Duration: Jan 4 2017Jan 8 2017

ASJC Scopus subject areas

  • Biomedical Engineering
  • Computational Theory and Mathematics

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