Internetwork connectivity of molecular networks across species of life

Mahajan, Tarun; Dar, Roy D

Background Molecular interactions have been studied as independent complex networks in systems biology. However, molecular networks dont exist independently of each other. In a network of networks approach (called multiplex), we uncover the design principles for the joint organization of transcriptional regulatory network (TRN) and protein-protein interaction (PPI) network. Results We find that TRN and PPI networks are non-randomly coupled in the TRN-PPI multiplex across five different eukaryotic species. Gene degrees in TRN (number of downstream genes) are positively correlated with protein degrees in PPI (number of interacting protein partners). Gene-gene interactions in TRN and protein-protein interactions in PPI also non-randomly overlap in the multiplex. These design principles are conserved across the five eukaryotic species. We show that the robustness of the TRN-PPI multiplex is dependent on these design principles. Further, functionally important genes and proteins, such as essential, disease-related and those involved in host-pathogen PPI networks, are preferentially situated in essential parts of the human multiplex with highly overlapping interactions. Conclusion We unveil the multiplex architecture of TRN and PPI networks across different species. Multiplex architecture may thus define a general framework for studying molecular networks across the different species of life. This approach may uncover the building blocks of the hierarchical organization of molecular interactions.