A Bayesian approach for structure learning in oscillating regulatory networks
This addresses a challenging problem in systems biology for researchers studying oscillatory processes like circadian rhythms, but it is incremental as it builds on existing frequency domain and Bayesian techniques.
The paper tackles the problem of determining the structure of interaction networks underlying biological oscillations in transcriptional regulatory networks, presenting a Bayesian method that leverages oscillatory signals and shows substantial improvements over competing approaches when the oscillatory assumption is met, with competitive performance otherwise.
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. 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.