Inference of Circadian Regulatory Networks

We assess the accuracy of various state-of-the-art methods for reconstructing gene and protein regulatory networks in the context of circadian regulation. Gene expression and protein concentration time series are simulated from a recently published regulatory network of the circadian clock in A. thaliana, which is mathematically described by a Markov jump process based on Michaelis-Menten kinetics. Our study provides relative network reconstruction accuracy scores for a critical comparative performance evaluation, quantifies the influence of systematically missing values related to unknown protein concentrations and mRNA transcription rates, and investigates the dependence of the performance on the network topology and the degree of recurrency. An application to recent gene expression time series from qPCR experiments suggests new hypotheses about the structure of the central circadian gene regulatory network in A. thaliana.