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Critical controllability in proteome-wide protein interaction network integrating transcriptome

Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in par...

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Autores principales: Ishitsuka, Masayuki, Akutsu, Tatsuya, Nacher, Jose C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819195/
https://www.ncbi.nlm.nih.gov/pubmed/27040162
http://dx.doi.org/10.1038/srep23541
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author Ishitsuka, Masayuki
Akutsu, Tatsuya
Nacher, Jose C.
author_facet Ishitsuka, Masayuki
Akutsu, Tatsuya
Nacher, Jose C.
author_sort Ishitsuka, Masayuki
collection PubMed
description Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development.
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spelling pubmed-48191952016-04-06 Critical controllability in proteome-wide protein interaction network integrating transcriptome Ishitsuka, Masayuki Akutsu, Tatsuya Nacher, Jose C. Sci Rep Article Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development. Nature Publishing Group 2016-04-04 /pmc/articles/PMC4819195/ /pubmed/27040162 http://dx.doi.org/10.1038/srep23541 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ishitsuka, Masayuki
Akutsu, Tatsuya
Nacher, Jose C.
Critical controllability in proteome-wide protein interaction network integrating transcriptome
title Critical controllability in proteome-wide protein interaction network integrating transcriptome
title_full Critical controllability in proteome-wide protein interaction network integrating transcriptome
title_fullStr Critical controllability in proteome-wide protein interaction network integrating transcriptome
title_full_unstemmed Critical controllability in proteome-wide protein interaction network integrating transcriptome
title_short Critical controllability in proteome-wide protein interaction network integrating transcriptome
title_sort critical controllability in proteome-wide protein interaction network integrating transcriptome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819195/
https://www.ncbi.nlm.nih.gov/pubmed/27040162
http://dx.doi.org/10.1038/srep23541
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