Improvements in the reconstruction of time-varying gene regulatory networks: Dynamic programming and regularization by information sharing among genes

Marco Grzegorczyk*, Dirk Husmeier*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

57 Citations (Scopus)

Abstract

Method: Dynamic Bayesian networks (DBNs) have been applied widely to reconstruct the structure of regulatory processes from time series data, and they have established themselves as a standard modelling tool in computational systems biology. The conventional approach is based on the assumption of a homogeneous Markov chain, and many recent research efforts have focused on relaxing this restriction. An approach that enjoys particular popularity is based on a combination of a DBN with a multiple changepoint process, and the application of a Bayesian inference scheme via reversible jump Markov chain Monte Carlo (RJMCMC). In the present article, we expand this approach in two ways. First, we show that a dynamic programming scheme allows the changepoints to be sampled from the correct conditional distribution, which results in improved convergence over RJMCMC. Second, we introduce a novel Bayesian clustering and information sharing scheme among nodes, which provides a mechanism for automatic model complexity tuning.

Results: We evaluate the dynamic programming scheme on expression time series for Arabidopsis thaliana genes involved in circadian regulation. In a simulation study we demonstrate that the regularization scheme improves the network reconstruction accuracy over that obtained with recently proposed inhomogeneous DBNs. For gene expression profiles from a synthetically designed Saccharomyces cerevisiae strain under switching carbon metabolism we show that the combination of both: dynamic programming and regularization yields an inference procedure that outperforms two alternative established network reconstruction methods from the biology literature.

Original languageEnglish
Pages (from-to)693-699
Number of pages7
JournalBioinformatics
Volume27
Issue number5
DOIs
Publication statusPublished - 1-Mar-2011

Keywords

  • DELAYS

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