A Bayesian approach for structure learning in oscillating regulatory networks

Bioinformatics. 2015 Nov 15;31(22):3617-24. doi: 10.1093/bioinformatics/btv414. Epub 2015 Jul 14.

Abstract

Motivation: Oscillations lie at the core of many biological processes, from the cell cycle, to circadian oscillations and developmental processes. Time-keeping mechanisms are essential to enable organisms to adapt to varying conditions in environmental cycles, from day/night to seasonal. Transcriptional regulatory networks are one of the mechanisms behind these biological oscillations. However, while identifying cyclically expressed genes from time series measurements is relatively easy, determining the structure of the interaction network underpinning the oscillation is a far more challenging problem.

Results: Here, we explicitly leverage the oscillatory nature of the transcriptional signals and present a method for reconstructing network interactions tailored to this special but important class of genetic circuits. Our method is based on projecting the signal onto a set of oscillatory basis functions using a Discrete Fourier Transform. We build a Bayesian Hierarchical model within a frequency domain linear model in order to enforce sparsity and incorporate prior knowledge about the network structure. Experiments on real and simulated data show that the method can lead to substantial improvements over competing approaches if the oscillatory assumption is met, and remains competitive also in cases it is not.

Availability: DSS, experiment scripts and data are available at http://homepages.inf.ed.ac.uk/gsanguin/DSS.zip.

Contact: d.trejo-banos@sms.ed.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics
  • Bayes Theorem
  • Cell Cycle / genetics
  • Circadian Clocks / genetics
  • Computer Simulation
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Gene Expression Regulation, Plant
  • Gene Regulatory Networks*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics