Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.

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 thou...

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Autores principales:	Elena Zotenko, Julian Mestre, Dianne P O'Leary, Teresa M Przytycka
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1dfc41e3c4764ca69958bda9fabf7220
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spelling	oai:doaj.org-article:1dfc41e3c4764ca69958bda9fabf72202021-11-25T05:41:11ZWhy do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.1553-734X1553-735810.1371/journal.pcbi.1000140https://doaj.org/article/1dfc41e3c4764ca69958bda9fabf72202008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18670624/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The 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.Elena ZotenkoJulian MestreDianne P O'LearyTeresa M PrzytyckaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 8, p e1000140 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Elena Zotenko Julian Mestre Dianne P O'Leary Teresa M Przytycka Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
description	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.
format	article
author	Elena Zotenko Julian Mestre Dianne P O'Leary Teresa M Przytycka
author_facet	Elena Zotenko Julian Mestre Dianne P O'Leary Teresa M Przytycka
author_sort	Elena Zotenko
title	Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
title_short	Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
title_full	Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
title_fullStr	Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
title_full_unstemmed	Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
title_sort	why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/1dfc41e3c4764ca69958bda9fabf7220
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Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality.

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