Cargando…

Controllability analysis of molecular pathways points to proteins that control the entire interaction network

Inputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Devkota, Prajwal, Wuchty, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031241/
https://www.ncbi.nlm.nih.gov/pubmed/32076007
http://dx.doi.org/10.1038/s41598-020-59717-6
_version_ 1783499334782812160
author Devkota, Prajwal
Wuchty, Stefan
author_facet Devkota, Prajwal
Wuchty, Stefan
author_sort Devkota, Prajwal
collection PubMed
description Inputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of proteins control a high number of pathways and vice versa. Transcending different topological levels, proteins that controlled a large number of pathways also controlled a network of interactions when all pathways were combined. Furthermore, control proteins that were robust when interactions were rewired or inverted also increasingly controlled an increasing number of pathways. As for functional characteristics, such control proteins were enriched with regulatory and signaling genes, disease genes and drug targets. Focusing on evolutionary characteristics, proteins that controlled different pathways had a penchant to be evolutionarily conserved as equal counterparts in other organisms, indicating the fundamental role that control analysis of pathways plays for our understanding of regulation, disease and evolution.
format Online
Article
Text
id pubmed-7031241
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-70312412020-02-26 Controllability analysis of molecular pathways points to proteins that control the entire interaction network Devkota, Prajwal Wuchty, Stefan Sci Rep Article Inputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of proteins control a high number of pathways and vice versa. Transcending different topological levels, proteins that controlled a large number of pathways also controlled a network of interactions when all pathways were combined. Furthermore, control proteins that were robust when interactions were rewired or inverted also increasingly controlled an increasing number of pathways. As for functional characteristics, such control proteins were enriched with regulatory and signaling genes, disease genes and drug targets. Focusing on evolutionary characteristics, proteins that controlled different pathways had a penchant to be evolutionarily conserved as equal counterparts in other organisms, indicating the fundamental role that control analysis of pathways plays for our understanding of regulation, disease and evolution. Nature Publishing Group UK 2020-02-19 /pmc/articles/PMC7031241/ /pubmed/32076007 http://dx.doi.org/10.1038/s41598-020-59717-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Devkota, Prajwal
Wuchty, Stefan
Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title_full Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title_fullStr Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title_full_unstemmed Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title_short Controllability analysis of molecular pathways points to proteins that control the entire interaction network
title_sort controllability analysis of molecular pathways points to proteins that control the entire interaction network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031241/
https://www.ncbi.nlm.nih.gov/pubmed/32076007
http://dx.doi.org/10.1038/s41598-020-59717-6
work_keys_str_mv AT devkotaprajwal controllabilityanalysisofmolecularpathwayspointstoproteinsthatcontroltheentireinteractionnetwork
AT wuchtystefan controllabilityanalysisofmolecularpathwayspointstoproteinsthatcontroltheentireinteractionnetwork