Why Do Hubs in the Yeast Protein Interaction Network Tend To Be Essential: Reexamining the Connection between the Network Topology and Essentiality
By Elena Zotenko, Julián Mestre, Dianne P. O'Leary, Teresa M. Przytycka. PLoS Comput. Biol., 2008
407 citations recorded by the source corpus.
The centrality-lethality rule, which notes that high-degree nodes in a protein interaction network tend to correspond to proteins that are essential, suggests that the topological prominence of a protein in a protein interaction network may be a good predictor of its biological importance. Even though the correlation between degree and essentiality was confirmed by many independent studies, the reason for this correlation remains illusive. Several hypotheses about putative connections between essentiality of hubs and the topology of protein–protein interaction networks have been proposed, but as we demonstrate, these explanations are not supported by the properties of protein interaction networks. To identify the main topological determinant of essentiality and to provide a biological explanation for the connection between the network topology and essentiality, we performed a rigorous analysis of six variants of the genomewide protein interaction network for Saccharomyces cerevisiae obtained using different techniques. We demonstrated that the majority of hubs are essential due to their involvement in Essential Complex Biological Modules, a group of densely connected proteins with shared biological function that are enriched in essential proteins. Moreover, we rejected two previously proposed explanations for the centrality-lethality rule, one relating the essentiality of hubs to their role in the overall network connectivity and another relying on the recently published essential protein interactions model.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2ffa623068f5388cad1919ae0e853e9fffcf8cd5
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
- Roded Sharan
- Trey Ideker
- Lenore J. Cowen
- Saket Navlakha
- Benjamin J. Raphael
- Ron Shamir
- Igor Ulitsky
- Anastasia Baryshnikova
Citations in the corpus
- Network propagation: a universal amplifier of genetic associations (2017, background): “…include ranking differentially expressed genes 61 , predicting gene essentiality and pleiotropy (that is, association with multiple phenotypes) 62,63 , identifying signalling-regulatory pathways 64,65 , predicting drug side effects 66 , reducing noise in PPI networks 67,68 , defining functional…”
- Learning the Structural Vocabulary of a Network (2017, background): “…how protein-protein interactions are perturbed due to node failures or environmental noise (Kitano, 2004; Albert, Jeong, & Barabasi, 2000; Barabasi & Oltvai, 2004; Alon, 2003; Zotenko, Mestre, O’Leary, & Przytycka, 2008), and how these perturbations can lead to disease (Barabasi et al., 2011).”
- Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia (2019, background): “Available theoretical and experimental evidence suggests that disruption of a network hub, or genes that regulate the hub, could alter the entire gene network 6,7,24,43 .”