Integrating external biological knowledge in the construction of regulatory networks from time-series expression data
1 Department of Microbiology, University of Washington, Box 358070, Seattle, WA, 98195, USA
2 Department of Statistics, University of Washington, Box 354320, Seattle, WA, 98195, USA
3 Department of Biochemistry, University of Washington, Box 357350, Seattle, WA, 98195, USA
4 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, 10029, USA
BMC Systems Biology 2012, 6:101 doi:10.1186/1752-0509-6-101Published: 16 August 2012
Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge.
We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA) variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models.
We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.