Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.

Metabolic network reconstructions represent valuable scaffolds for '-omics' data integration and are used to computationally interrogate network properties. However, they do not explicitly account for the synthesis of macromolecules (i.e., proteins and RNA). Here, we present the first geno...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ines Thiele, Neema Jamshidi, Ronan M T Fleming, Bernhard Ø Palsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1466f5970cd145adbc6b2f632a4ea199
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1466f5970cd145adbc6b2f632a4ea199
record_format	dspace
spelling	oai:doaj.org-article:1466f5970cd145adbc6b2f632a4ea1992021-11-25T05:41:47ZGenome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.1553-734X1553-735810.1371/journal.pcbi.1000312https://doaj.org/article/1466f5970cd145adbc6b2f632a4ea1992009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19282977/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Metabolic network reconstructions represent valuable scaffolds for '-omics' data integration and are used to computationally interrogate network properties. However, they do not explicitly account for the synthesis of macromolecules (i.e., proteins and RNA). Here, we present the first genome-scale, fine-grained reconstruction of Escherichia coli's transcriptional and translational machinery, which produces 423 functional gene products in a sequence-specific manner and accounts for all necessary chemical transformations. Legacy data from over 500 publications and three databases were reviewed, and many pathways were considered, including stable RNA maturation and modification, protein complex formation, and iron-sulfur cluster biogenesis. This reconstruction represents the most comprehensive knowledge base for these important cellular functions in E. coli and is unique in its scope. Furthermore, it was converted into a mathematical model and used to: (1) quantitatively integrate gene expression data as reaction constraints and (2) compute functional network states, which were compared to reported experimental data. For example, the model predicted accurately the ribosome production, without any parameterization. Also, in silico rRNA operon deletion suggested that a high RNA polymerase density on the remaining rRNA operons is needed to reproduce the reported experimental ribosome numbers. Moreover, functional protein modules were determined, and many were found to contain gene products from multiple subsystems, highlighting the functional interaction of these proteins. This genome-scale reconstruction of E. coli's transcriptional and translational machinery presents a milestone in systems biology because it will enable quantitative integration of '-omics' datasets and thus the study of the mechanistic principles underlying the genotype-phenotype relationship.Ines ThieleNeema JamshidiRonan M T FlemingBernhard Ø PalssonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 3, p e1000312 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ines Thiele Neema Jamshidi Ronan M T Fleming Bernhard Ø Palsson Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
description	Metabolic network reconstructions represent valuable scaffolds for '-omics' data integration and are used to computationally interrogate network properties. However, they do not explicitly account for the synthesis of macromolecules (i.e., proteins and RNA). Here, we present the first genome-scale, fine-grained reconstruction of Escherichia coli's transcriptional and translational machinery, which produces 423 functional gene products in a sequence-specific manner and accounts for all necessary chemical transformations. Legacy data from over 500 publications and three databases were reviewed, and many pathways were considered, including stable RNA maturation and modification, protein complex formation, and iron-sulfur cluster biogenesis. This reconstruction represents the most comprehensive knowledge base for these important cellular functions in E. coli and is unique in its scope. Furthermore, it was converted into a mathematical model and used to: (1) quantitatively integrate gene expression data as reaction constraints and (2) compute functional network states, which were compared to reported experimental data. For example, the model predicted accurately the ribosome production, without any parameterization. Also, in silico rRNA operon deletion suggested that a high RNA polymerase density on the remaining rRNA operons is needed to reproduce the reported experimental ribosome numbers. Moreover, functional protein modules were determined, and many were found to contain gene products from multiple subsystems, highlighting the functional interaction of these proteins. This genome-scale reconstruction of E. coli's transcriptional and translational machinery presents a milestone in systems biology because it will enable quantitative integration of '-omics' datasets and thus the study of the mechanistic principles underlying the genotype-phenotype relationship.
format	article
author	Ines Thiele Neema Jamshidi Ronan M T Fleming Bernhard Ø Palsson
author_facet	Ines Thiele Neema Jamshidi Ronan M T Fleming Bernhard Ø Palsson
author_sort	Ines Thiele
title	Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
title_short	Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
title_full	Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
title_fullStr	Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
title_full_unstemmed	Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
title_sort	genome-scale reconstruction of escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/1466f5970cd145adbc6b2f632a4ea199
work_keys_str_mv	AT inesthiele genomescalereconstructionofescherichiacolistranscriptionalandtranslationalmachineryaknowledgebaseitsmathematicalformulationanditsfunctionalcharacterization AT neemajamshidi genomescalereconstructionofescherichiacolistranscriptionalandtranslationalmachineryaknowledgebaseitsmathematicalformulationanditsfunctionalcharacterization AT ronanmtfleming genomescalereconstructionofescherichiacolistranscriptionalandtranslationalmachineryaknowledgebaseitsmathematicalformulationanditsfunctionalcharacterization AT bernhardøpalsson genomescalereconstructionofescherichiacolistranscriptionalandtranslationalmachineryaknowledgebaseitsmathematicalformulationanditsfunctionalcharacterization
_version_	1718414501453234176

Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.

Ejemplares similares