An expanded protein-protein interaction network in Bacillus subtilis reveals a group of hubs: Exploration by an integrative approach.

We have generated a protein-protein interaction network in Bacillus subtilis focused on several essential cellular processes such as cell division, cell responses to various stresses, the bacterial cytoskeleton, DNA replication and chromosome maintenance by careful application of the yeast two-hybrid approach. This network, composed of 793 interactions linking 287 proteins with an average connectivity of five interactions per protein, represents a valuable resource for future functional analyses. A striking feature of the network is a group of highly connected hubs (GoH) linking many different cellular processes. Most of the proteins of the GoH have unknown functions and are associated to the membrane. By the integration of available knowledge, in particular of transcriptome data sets, the GoH was decomposed into subgroups of party hubs corresponding to protein complexes or regulatory pathways expressed under different conditions. At a global level, the GoH might function as a very robust group of date hubs having partially redundant functions to integrate information from the different cellular pathways. Our analyses also provide a rational way to study the highly redundant functions of the GoH by a genetic approach.