Identification of Gene Networks with Time Delayed Regulation Based on Temporal Expression Profiles

Abstract

There are fundamental limitations in inferring the functional interaction structure of a gene (regulatory) network only from sequence information such as binding motifs. To overcome such limitations, various approaches have been developed to infer the functional interaction structure from expression profiles. However, most of them have not been so successful due to the experimental limitations and computational complexity. Hence, there is a pressing need to develop a simple but effective methodology that can systematically identify the functional interaction structure of a gene network from time-series expression profiles. In particular, we need to take into account the different time delay effects in gene regulation since they are ubiquitously present. We have considered a new experiment that measures the overall expression changes after a perturbation on a specific gene. Based on this experiment, we have proposed a new inference method that can take account of the time delay induced while the perturbation affects its primary target genes. Specifically, we have developed an algebraic equation from which we can identify the subnetwork structure around the perturbed gene. We have also analyzed the influence of time delay on the inferred network structure. The proposed method is particularly useful for identification of a gene network with small variations in the time delay of gene regulation.