Topology of Transcriptional Regulatory Networks: Testing and Improving

With the increasing amount and complexity of data generated in biological experiments it is becoming necessary to enhance the performance and applicability of existing statistical data analysis methods. This enhancement is needed for the hidden biological information to be better resolved and better interpreted. Towards that aim, systematic incorporation of prior information in biological data analysis has been a challenging problem for systems biology. Several methods have been proposed to integrate data from different levels of information most notably from metabolomics, transcriptomics and proteomics and thus enhance biological interpretation. However, in order not to be misled by the dominance of incorrect prior information in the analysis, being able to discriminate between competing prior information is required. In this study, we show that discrimination between topological information in competing transcriptional regulatory network models is possible solely based on experimental data. We use network topology dependent decomposition of synthetic gene expression data to introduce both local and global discriminating measures. The measures indicate how well the gene expression data can be explained under the constraints of the model network topology and how much each regulatory connection in the model refuses to be constrained. Application of the method to the cell cycle regulatory network of Saccharomyces cerevisiae leads to the prediction of novel regulatory interactions, improving the information content of the hypothesized network model.