Understanding gene essentiality by finely characterizing hubs in the yeast protein interaction network

The centrality–lethality rule, i.e., high-degree proteins or hubs tend to be more essential than low-degree proteins in the yeast protein interaction network, reveals that a protein’s central position indicates its important function, but whether and why hubs tend to be more essential have been heavily debated. Here, we integrated gene expression and functional module data to classify hubs into four types: non-co-expressed non-co-cluster hubs, non-co-expressed co-cluster hubs, co-expressed non-co-cluster hubs and co-expressed co-cluster hubs. We found that all the four hub types are more essential than non-hubs, but they also show different enrichments in essential proteins. Non-co-expressed non-co-cluster hubs play key role in organizing different modules formed by the other three hub types, but they are less important to the survival of the yeast cell. Among the four hub types, co-expressed co-cluster hubs, which likely correspond to the core components of stable protein complexes, are the most essential. These results demonstrated that our classification of hubs into four types could better improve the understanding of gene essentiality.

Research highlights
► High-degree proteins or hubs tend to be more essential than low-degree proteins in the yeast protein interaction network.
► Intermodular hubs tend to be global connectors, while intramodular hubs tend to form local modules.
► The yeast protein network tends to be tolerant to intramodular hub attack, but the yeast cell tends to die upon the deletion of intramodular hub genes.
► The majority of hubs are essential due to their local role as core components of functional modules or complexes, but not due to their global role in organizing the whole network.