Reconstruction of biological networks by incorporating prior knowledge into Bayesian network models

Bayesian network model is widely used for reverse engineering of biological network structures. An advantage of this model is its capability to integrate prior knowledge into the model learning process, which can lead to improving the quality of the network reconstruction outcome. Some previous works have explored this area with focus on using prior knowledge of the direct molecular links, except for a few recent ones proposing to examine the effects of molecular orderings. In this study, we propose a Bayesian network model that can integrate both direct links and orderings into the model. Random weights are assigned to these two types of prior knowledge to alleviate bias toward certain types of information. We evaluate our model performance using both synthetic data and biological data for the RAF signaling network, and illustrate the significant improvement on network structure reconstruction of the proposing models over the existing methods. We also examine the correlation between the improvement and the abundance of ordering prior knowledge. To address the issue of generating prior knowledge, we propose an approach to automatically extract potential molecular orderings from knowledge resources such as Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Gene Ontology (GO) annotation.