Reconstruction of gene networks using prior knowledge

Abstract

Background: Reconstructing gene regulatory networks (GRNs) from expression data is a challenging task that has become essential to the understanding of complex regulatory mechanisms in cells. The major issues are the usually very high ratio of number of genes to sample size, and the noise in the available data. Integrating biological prior knowledge to the learning process is a natural and promising way to partially compensate for the lack of reliable expression data and to increase the accuracy of network reconstruction algorithms. Results: In this manuscript, we present PriorPC, a new algorithm based on the PC algorithm. PC algorithm is one of the most popular methods for Bayesian network reconstruction. The result of PC is known to depend on the order in which conditional independence tests are processed, especially for large networks. PriorPC uses prior knowledge to exclude unlikely edges from network estimation and introduces a particular ordering for the conditional independence tests. We show on synthetic data that the structural accuracy of networks obtained with PriorPC is greatly improved compared to PC. Conclusion: PriorPC improves structural accuracy of inferred gene networks by using soft priors which assign to edges a probability of existence. It is robust to false prior which is not avoidable in the context of biological data. PriorPC is also fast and scales well for large networks which is important for its applicability to real data.