Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1.

Richard Bonneau, Nitin S. Baliga, Eric W. Deutsch, Paul Shannon, Leroy Hood

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Large fractions of all fully sequenced genomes code for proteins of unknown function. Annotating these proteins of unknown function remains a critical bottleneck for systems biology and is crucial to understanding the biological relevance of genome-wide changes in mRNA and protein expression, protein-protein and protein-DNA interactions. The work reported here demonstrates that de novo structure prediction is now a viable option for providing general function information for many proteins of unknown function. RESULTS: We have used Rosetta de novo structure prediction to predict three-dimensional structures for 1,185 proteins and protein domains (<150 residues in length) found in Halobacterium NRC-1, a widely studied halophilic archaeon. Predicted structures were searched against the Protein Data Bank to identify fold similarities and extrapolate putative functions. They were analyzed in the context of a predicted association network composed of several sources of functional associations such as: predicted protein interactions, predicted operons, phylogenetic profile similarity and domain fusion. To illustrate this approach, we highlight three cases where our combined procedure has provided novel insights into our understanding of chemotaxis, possible prophage remnants in Halobacterium NRC-1 and archaeal transcriptional regulators. CONCLUSIONS: Simultaneous analysis of the association network, coordinated mRNA level changes in microarray experiments and genome-wide structure prediction has allowed us to glean significant biological insights into the roles of several Halobacterium NRC-1 proteins of previously unknown function, and significantly reduce the number of proteins encoded in the genome of this haloarchaeon for which no annotation is available.

Original languageEnglish (US)
JournalGenome Biology
Volume5
Issue number8
StatePublished - 2004

Fingerprint

Halobacterium
Systems Biology
Archaea
Biological Sciences
protein
prediction
Proteins
proteins
genome
Genome
Prophages
Messenger RNA
chemotaxis
Chemotaxis
operon
Operon

ASJC Scopus subject areas

  • Genetics

Cite this

Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1. / Bonneau, Richard; Baliga, Nitin S.; Deutsch, Eric W.; Shannon, Paul; Hood, Leroy.

In: Genome Biology, Vol. 5, No. 8, 2004.

Research output: Contribution to journalArticle

Bonneau, Richard ; Baliga, Nitin S. ; Deutsch, Eric W. ; Shannon, Paul ; Hood, Leroy. / Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1. In: Genome Biology. 2004 ; Vol. 5, No. 8.
@article{b9594c12b87b4700acb5e8a0c290ab40,
title = "Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1.",
abstract = "BACKGROUND: Large fractions of all fully sequenced genomes code for proteins of unknown function. Annotating these proteins of unknown function remains a critical bottleneck for systems biology and is crucial to understanding the biological relevance of genome-wide changes in mRNA and protein expression, protein-protein and protein-DNA interactions. The work reported here demonstrates that de novo structure prediction is now a viable option for providing general function information for many proteins of unknown function. RESULTS: We have used Rosetta de novo structure prediction to predict three-dimensional structures for 1,185 proteins and protein domains (<150 residues in length) found in Halobacterium NRC-1, a widely studied halophilic archaeon. Predicted structures were searched against the Protein Data Bank to identify fold similarities and extrapolate putative functions. They were analyzed in the context of a predicted association network composed of several sources of functional associations such as: predicted protein interactions, predicted operons, phylogenetic profile similarity and domain fusion. To illustrate this approach, we highlight three cases where our combined procedure has provided novel insights into our understanding of chemotaxis, possible prophage remnants in Halobacterium NRC-1 and archaeal transcriptional regulators. CONCLUSIONS: Simultaneous analysis of the association network, coordinated mRNA level changes in microarray experiments and genome-wide structure prediction has allowed us to glean significant biological insights into the roles of several Halobacterium NRC-1 proteins of previously unknown function, and significantly reduce the number of proteins encoded in the genome of this haloarchaeon for which no annotation is available.",
author = "Richard Bonneau and Baliga, {Nitin S.} and Deutsch, {Eric W.} and Paul Shannon and Leroy Hood",
year = "2004",
language = "English (US)",
volume = "5",
journal = "Genome Biology",
issn = "1474-7596",
publisher = "BioMed Central",
number = "8",

}

TY - JOUR

T1 - Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1.

AU - Bonneau, Richard

AU - Baliga, Nitin S.

AU - Deutsch, Eric W.

AU - Shannon, Paul

AU - Hood, Leroy

PY - 2004

Y1 - 2004

N2 - BACKGROUND: Large fractions of all fully sequenced genomes code for proteins of unknown function. Annotating these proteins of unknown function remains a critical bottleneck for systems biology and is crucial to understanding the biological relevance of genome-wide changes in mRNA and protein expression, protein-protein and protein-DNA interactions. The work reported here demonstrates that de novo structure prediction is now a viable option for providing general function information for many proteins of unknown function. RESULTS: We have used Rosetta de novo structure prediction to predict three-dimensional structures for 1,185 proteins and protein domains (<150 residues in length) found in Halobacterium NRC-1, a widely studied halophilic archaeon. Predicted structures were searched against the Protein Data Bank to identify fold similarities and extrapolate putative functions. They were analyzed in the context of a predicted association network composed of several sources of functional associations such as: predicted protein interactions, predicted operons, phylogenetic profile similarity and domain fusion. To illustrate this approach, we highlight three cases where our combined procedure has provided novel insights into our understanding of chemotaxis, possible prophage remnants in Halobacterium NRC-1 and archaeal transcriptional regulators. CONCLUSIONS: Simultaneous analysis of the association network, coordinated mRNA level changes in microarray experiments and genome-wide structure prediction has allowed us to glean significant biological insights into the roles of several Halobacterium NRC-1 proteins of previously unknown function, and significantly reduce the number of proteins encoded in the genome of this haloarchaeon for which no annotation is available.

AB - BACKGROUND: Large fractions of all fully sequenced genomes code for proteins of unknown function. Annotating these proteins of unknown function remains a critical bottleneck for systems biology and is crucial to understanding the biological relevance of genome-wide changes in mRNA and protein expression, protein-protein and protein-DNA interactions. The work reported here demonstrates that de novo structure prediction is now a viable option for providing general function information for many proteins of unknown function. RESULTS: We have used Rosetta de novo structure prediction to predict three-dimensional structures for 1,185 proteins and protein domains (<150 residues in length) found in Halobacterium NRC-1, a widely studied halophilic archaeon. Predicted structures were searched against the Protein Data Bank to identify fold similarities and extrapolate putative functions. They were analyzed in the context of a predicted association network composed of several sources of functional associations such as: predicted protein interactions, predicted operons, phylogenetic profile similarity and domain fusion. To illustrate this approach, we highlight three cases where our combined procedure has provided novel insights into our understanding of chemotaxis, possible prophage remnants in Halobacterium NRC-1 and archaeal transcriptional regulators. CONCLUSIONS: Simultaneous analysis of the association network, coordinated mRNA level changes in microarray experiments and genome-wide structure prediction has allowed us to glean significant biological insights into the roles of several Halobacterium NRC-1 proteins of previously unknown function, and significantly reduce the number of proteins encoded in the genome of this haloarchaeon for which no annotation is available.

UR - http://www.scopus.com/inward/record.url?scp=10044281116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10044281116&partnerID=8YFLogxK

M3 - Article

VL - 5

JO - Genome Biology

JF - Genome Biology

SN - 1474-7596

IS - 8

ER -