Global versus Local Hubs in Human Protein-Protein Interaction Network

In this study, we have constructed tissue-specific protein protein interaction networks for 70 human tissues and have identified three types of hubs based on their expression breadths: (a) tissue-specific hubs (TSHs) (proteins that are expressed in <= 10 tissues and also form hubs in <= 10 tissues), (b) tissue-preferred hubs (TPHs) (proteins expressed in >= 60 tissues but are highly connected in <= 10 tissues), and (c) housekeeping hubs (HKHs) (proteins that are expressed in >= 60 tissues and also form hubs in >= 60 tissues). Comparative analyses revealed significant differences between TSHs and HKHs and also revealed that TPHs behave more like HKHs. TSHs are lengthier, more disordered, and also quickly evolving proteins as compared with HKHs. Despite having a similar number of binding surfaces and interacting domains, TSHs are associated with a lower degree of centrality as compared with HKHs, suggesting that TSHs are unsaturated with regard to their binding capability and are perhaps evolving with regard to their interactions. TSHs are less abundantly expressed as compared with HKHs and are enriched with PEST motifs, indicating their tight regulation. All of these properties of TSHs and HKHs correlate with their distinct functional roles; TSHs are involved in tissue-specific functional roles, viz., secretors, receptors, and signaling proteins, whereas HKHs are involved in core-cellular functions such as transcription, translation, and so on. Our study, therefore, brings forth a clear and distinct classification of hubs simply based on their expression breadth and further assumes significance in the light of the highly debated dichotomy of date and party hubs, which is based on the coexpression pattern of hubs with their partners.