A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.

Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs) is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is becaus...

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Autores principales:	Tammy M K Cheng, Lucas Goehring, Linda Jeffery, Yu-En Lu, Jacqueline Hayles, Béla Novák, Paul A Bates
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cbe6b368acf14614882175ae25be8929
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spelling	oai:doaj.org-article:cbe6b368acf14614882175ae25be89292021-11-18T05:52:46ZA structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.1553-734X1553-735810.1371/journal.pcbi.1002738https://doaj.org/article/cbe6b368acf14614882175ae25be89292012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23093928/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs) is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is because complex information at both the protein and pathway level has to be integrated. Given that the idea of integrating both protein and pathway dynamics to estimate the systemic impact of missense mutations in proteins remains predominantly unexplored, we investigate the practicality of such an approach by formulating mathematical models and comparing them with experimental data to study missense mutations. We present two case studies: (1) interpreting systemic perturbation for mutations within the cell cycle control mechanisms (G2 to mitosis transition) for yeast; (2) phenotypic classification of neuron-related human diseases associated with mutations within the mitogen-activated protein kinase (MAPK) pathway. We show that the application of simplified mathematical models is feasible for understanding the effects of small sequence changes on cellular behavior. Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation.Tammy M K ChengLucas GoehringLinda JefferyYu-En LuJacqueline HaylesBéla NovákPaul A BatesPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 10, p e1002738 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Tammy M K Cheng Lucas Goehring Linda Jeffery Yu-En Lu Jacqueline Hayles Béla Novák Paul A Bates A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
description	Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs) is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is because complex information at both the protein and pathway level has to be integrated. Given that the idea of integrating both protein and pathway dynamics to estimate the systemic impact of missense mutations in proteins remains predominantly unexplored, we investigate the practicality of such an approach by formulating mathematical models and comparing them with experimental data to study missense mutations. We present two case studies: (1) interpreting systemic perturbation for mutations within the cell cycle control mechanisms (G2 to mitosis transition) for yeast; (2) phenotypic classification of neuron-related human diseases associated with mutations within the mitogen-activated protein kinase (MAPK) pathway. We show that the application of simplified mathematical models is feasible for understanding the effects of small sequence changes on cellular behavior. Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation.
format	article
author	Tammy M K Cheng Lucas Goehring Linda Jeffery Yu-En Lu Jacqueline Hayles Béla Novák Paul A Bates
author_facet	Tammy M K Cheng Lucas Goehring Linda Jeffery Yu-En Lu Jacqueline Hayles Béla Novák Paul A Bates
author_sort	Tammy M K Cheng
title	A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
title_short	A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
title_full	A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
title_fullStr	A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
title_full_unstemmed	A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
title_sort	structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cbe6b368acf14614882175ae25be8929
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A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.

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