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Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks

BACKGROUND: Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework...

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Detalles Bibliográficos
Autores principales: Wolfe, Cecily J, Kohane, Isaac S, Butte, Atul J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1239911/
https://www.ncbi.nlm.nih.gov/pubmed/16162296
http://dx.doi.org/10.1186/1471-2105-6-227
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author Wolfe, Cecily J
Kohane, Isaac S
Butte, Atul J
author_facet Wolfe, Cecily J
Kohane, Isaac S
Butte, Atul J
author_sort Wolfe, Cecily J
collection PubMed
description BACKGROUND: Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA) heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. RESULTS: We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO)? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. CONCLUSION: We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing whether pairs of functions operate together.
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spelling pubmed-12399112005-10-03 Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks Wolfe, Cecily J Kohane, Isaac S Butte, Atul J BMC Bioinformatics Research Article BACKGROUND: Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA) heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. RESULTS: We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO)? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. CONCLUSION: We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing whether pairs of functions operate together. BioMed Central 2005-09-14 /pmc/articles/PMC1239911/ /pubmed/16162296 http://dx.doi.org/10.1186/1471-2105-6-227 Text en Copyright © 2005 Wolfe et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wolfe, Cecily J
Kohane, Isaac S
Butte, Atul J
Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title_full Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title_fullStr Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title_full_unstemmed Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title_short Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
title_sort systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1239911/
https://www.ncbi.nlm.nih.gov/pubmed/16162296
http://dx.doi.org/10.1186/1471-2105-6-227
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