Epistasis in a model of molecular signal transduction.

Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we st...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alain Pumir, Boris Shraiman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cc73f34d1b3f44b69444852286386818
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cc73f34d1b3f44b69444852286386818
record_format	dspace
spelling	oai:doaj.org-article:cc73f34d1b3f44b694448522863868182021-11-18T05:50:32ZEpistasis in a model of molecular signal transduction.1553-734X1553-735810.1371/journal.pcbi.1001134https://doaj.org/article/cc73f34d1b3f44b694448522863868182011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21589889/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in terms of relating genotypes to phenotypes: to what extent does the effect of a genetic variation at one locus depend on genetic variation at all other loci? Systematic quantitative measurements of epistasis--the deviation from additivity in the effect of alleles at different loci--on a given quantitative trait remain a major challenge. Here, we take a complementary approach of studying theoretically the effect of varying multiple parameters in a validated model of molecular signal transduction. To connect with the genotype/phenotype mapping we interpret parameters of the model as different loci with discrete choices of these parameters as alleles, which allows us to systematically examine the dependence of the signaling output--a quantitative trait--on the set of possible allelic combinations. We show quite generally that quantitative traits behave approximately additively (weak epistasis) when alleles correspond to small changes of parameters; epistasis appears as a result of large differences between alleles. When epistasis is relatively strong, it is concentrated in a sparse subset of loci and in low order (e.g. pair-wise) interactions. We find that focusing on interaction between loci that exhibit strong additive effects is an efficient way of identifying most of the epistasis. Our model study defines a theoretical framework for interpretation of experimental data and provides statistical predictions for the structure of genetic interaction expected for moderately complex biological circuits.Alain PumirBoris ShraimanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 5, p e1001134 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Alain Pumir Boris Shraiman Epistasis in a model of molecular signal transduction.
description	Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in terms of relating genotypes to phenotypes: to what extent does the effect of a genetic variation at one locus depend on genetic variation at all other loci? Systematic quantitative measurements of epistasis--the deviation from additivity in the effect of alleles at different loci--on a given quantitative trait remain a major challenge. Here, we take a complementary approach of studying theoretically the effect of varying multiple parameters in a validated model of molecular signal transduction. To connect with the genotype/phenotype mapping we interpret parameters of the model as different loci with discrete choices of these parameters as alleles, which allows us to systematically examine the dependence of the signaling output--a quantitative trait--on the set of possible allelic combinations. We show quite generally that quantitative traits behave approximately additively (weak epistasis) when alleles correspond to small changes of parameters; epistasis appears as a result of large differences between alleles. When epistasis is relatively strong, it is concentrated in a sparse subset of loci and in low order (e.g. pair-wise) interactions. We find that focusing on interaction between loci that exhibit strong additive effects is an efficient way of identifying most of the epistasis. Our model study defines a theoretical framework for interpretation of experimental data and provides statistical predictions for the structure of genetic interaction expected for moderately complex biological circuits.
format	article
author	Alain Pumir Boris Shraiman
author_facet	Alain Pumir Boris Shraiman
author_sort	Alain Pumir
title	Epistasis in a model of molecular signal transduction.
title_short	Epistasis in a model of molecular signal transduction.
title_full	Epistasis in a model of molecular signal transduction.
title_fullStr	Epistasis in a model of molecular signal transduction.
title_full_unstemmed	Epistasis in a model of molecular signal transduction.
title_sort	epistasis in a model of molecular signal transduction.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cc73f34d1b3f44b69444852286386818
work_keys_str_mv	AT alainpumir epistasisinamodelofmolecularsignaltransduction AT borisshraiman epistasisinamodelofmolecularsignaltransduction
_version_	1718424816975872000

Epistasis in a model of molecular signal transduction.

Ejemplares similares