Cargando…

Protein interaction networks as metric spaces: a novel perspective on distribution of hubs

BACKGROUND: In the post-genomic era, a central and overarching question in the analysis of protein-protein interaction networks continues to be whether biological characteristics and functions of proteins such as lethality, physiological malfunctions and malignancy are intimately linked to the topol...

Descripción completa

Detalles Bibliográficos
Autores principales: Fadhal, Emad, Gamieldien, Junaid, Mwambene, Eric C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902029/
https://www.ncbi.nlm.nih.gov/pubmed/24438364
http://dx.doi.org/10.1186/1752-0509-8-6
_version_ 1782300942147780608
author Fadhal, Emad
Gamieldien, Junaid
Mwambene, Eric C
author_facet Fadhal, Emad
Gamieldien, Junaid
Mwambene, Eric C
author_sort Fadhal, Emad
collection PubMed
description BACKGROUND: In the post-genomic era, a central and overarching question in the analysis of protein-protein interaction networks continues to be whether biological characteristics and functions of proteins such as lethality, physiological malfunctions and malignancy are intimately linked to the topological role proteins play in the network as a mathematical structure. One of the key features that have implicitly been presumed is the existence of hubs, highly connected proteins considered to play a crucial role in biological networks. We explore the structure of protein interaction networks of a number of organisms as metric spaces and show that hubs are non randomly positioned and, from a distance point of view, centrally located. RESULTS: By analysing how the human functional protein interaction network, the human signalling network, Saccharomyces cerevisiae, Arabidopsis thaliana and Escherichia coli protein-protein interaction networks from various databases are distributed as metric spaces, we found that proteins interact radially through a central node, high degree proteins coagulate in the centre of the network, and those far away from the centre have low degree. We further found that the distribution of proteins from the centre is in some hierarchy of importance and has biological significance. CONCLUSIONS: We conclude that structurally, protein interaction networks are mathematical entities that share properties between organisms but not necessarily with other networks that follow power-law. We therefore conclude that (i) if there are hubs defined by degree, they are not distributed randomly; (ii) zones closest to the centre of the network are enriched for critically important proteins and are also functionally very specialised for specific 'house keeping’ functions; (iii) proteins closest to the network centre are functionally less dispensable and may present good targets for therapy development; and (iv) network biology requires its own network theory modelled on actual biological evidence and that simply adopting theories from the social sciences may be misleading.
format Online
Article
Text
id pubmed-3902029
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-39020292014-01-26 Protein interaction networks as metric spaces: a novel perspective on distribution of hubs Fadhal, Emad Gamieldien, Junaid Mwambene, Eric C BMC Syst Biol Research Article BACKGROUND: In the post-genomic era, a central and overarching question in the analysis of protein-protein interaction networks continues to be whether biological characteristics and functions of proteins such as lethality, physiological malfunctions and malignancy are intimately linked to the topological role proteins play in the network as a mathematical structure. One of the key features that have implicitly been presumed is the existence of hubs, highly connected proteins considered to play a crucial role in biological networks. We explore the structure of protein interaction networks of a number of organisms as metric spaces and show that hubs are non randomly positioned and, from a distance point of view, centrally located. RESULTS: By analysing how the human functional protein interaction network, the human signalling network, Saccharomyces cerevisiae, Arabidopsis thaliana and Escherichia coli protein-protein interaction networks from various databases are distributed as metric spaces, we found that proteins interact radially through a central node, high degree proteins coagulate in the centre of the network, and those far away from the centre have low degree. We further found that the distribution of proteins from the centre is in some hierarchy of importance and has biological significance. CONCLUSIONS: We conclude that structurally, protein interaction networks are mathematical entities that share properties between organisms but not necessarily with other networks that follow power-law. We therefore conclude that (i) if there are hubs defined by degree, they are not distributed randomly; (ii) zones closest to the centre of the network are enriched for critically important proteins and are also functionally very specialised for specific 'house keeping’ functions; (iii) proteins closest to the network centre are functionally less dispensable and may present good targets for therapy development; and (iv) network biology requires its own network theory modelled on actual biological evidence and that simply adopting theories from the social sciences may be misleading. BioMed Central 2014-01-18 /pmc/articles/PMC3902029/ /pubmed/24438364 http://dx.doi.org/10.1186/1752-0509-8-6 Text en Copyright © 2014 Fadhal et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fadhal, Emad
Gamieldien, Junaid
Mwambene, Eric C
Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title_full Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title_fullStr Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title_full_unstemmed Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title_short Protein interaction networks as metric spaces: a novel perspective on distribution of hubs
title_sort protein interaction networks as metric spaces: a novel perspective on distribution of hubs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902029/
https://www.ncbi.nlm.nih.gov/pubmed/24438364
http://dx.doi.org/10.1186/1752-0509-8-6
work_keys_str_mv AT fadhalemad proteininteractionnetworksasmetricspacesanovelperspectiveondistributionofhubs
AT gamieldienjunaid proteininteractionnetworksasmetricspacesanovelperspectiveondistributionofhubs
AT mwambeneericc proteininteractionnetworksasmetricspacesanovelperspectiveondistributionofhubs