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Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast
Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how g...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649002/ https://www.ncbi.nlm.nih.gov/pubmed/19300475 http://dx.doi.org/10.1371/journal.pcbi.1000311 |
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author | Ye, Chun Galbraith, Simon J. Liao, James C. Eskin, Eleazar |
author_facet | Ye, Chun Galbraith, Simon J. Liao, James C. Eskin, Eleazar |
author_sort | Ye, Chun |
collection | PubMed |
description | Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how genetic variations perturb the underlying transcription regulatory networks to induce differential gene expression. In this study, we describe a simple model of transcription regulation where the expression of a gene is completely characterized by two properties: the concentrations and promoter affinities of active transcription factors. We devise a method that extends Network Component Analysis (NCA) to determine how genetic variations in the form of single nucleotide polymorphisms (SNPs) perturb these two properties. Applying our method to a segregating population of Saccharomyces cerevisiae, we found statistically significant examples of trans-acting SNPs located in regulatory hotspots that perturb transcription factor concentrations and affinities for target promoters to cause global differential expression and cis-acting genetic variations that perturb the promoter affinities of transcription factors on a single gene to cause local differential expression. Although many genetic variations linked to gene expressions have been identified, it is not clear how they perturb the underlying regulatory networks that govern gene expression. Our work begins to fill this void by showing that many genetic variations affect the concentrations of active transcription factors in a cell and their affinities for target promoters. Understanding the effects of these perturbations can help us to paint a more complete picture of the complex landscape of transcription regulation. The software package implementing the algorithms discussed in this work is available as a MATLAB package upon request. |
format | Text |
id | pubmed-2649002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26490022009-03-20 Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast Ye, Chun Galbraith, Simon J. Liao, James C. Eskin, Eleazar PLoS Comput Biol Research Article Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how genetic variations perturb the underlying transcription regulatory networks to induce differential gene expression. In this study, we describe a simple model of transcription regulation where the expression of a gene is completely characterized by two properties: the concentrations and promoter affinities of active transcription factors. We devise a method that extends Network Component Analysis (NCA) to determine how genetic variations in the form of single nucleotide polymorphisms (SNPs) perturb these two properties. Applying our method to a segregating population of Saccharomyces cerevisiae, we found statistically significant examples of trans-acting SNPs located in regulatory hotspots that perturb transcription factor concentrations and affinities for target promoters to cause global differential expression and cis-acting genetic variations that perturb the promoter affinities of transcription factors on a single gene to cause local differential expression. Although many genetic variations linked to gene expressions have been identified, it is not clear how they perturb the underlying regulatory networks that govern gene expression. Our work begins to fill this void by showing that many genetic variations affect the concentrations of active transcription factors in a cell and their affinities for target promoters. Understanding the effects of these perturbations can help us to paint a more complete picture of the complex landscape of transcription regulation. The software package implementing the algorithms discussed in this work is available as a MATLAB package upon request. Public Library of Science 2009-03-20 /pmc/articles/PMC2649002/ /pubmed/19300475 http://dx.doi.org/10.1371/journal.pcbi.1000311 Text en Ye et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ye, Chun Galbraith, Simon J. Liao, James C. Eskin, Eleazar Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title | Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title_full | Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title_fullStr | Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title_full_unstemmed | Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title_short | Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast |
title_sort | using network component analysis to dissect regulatory networks mediated by transcription factors in yeast |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649002/ https://www.ncbi.nlm.nih.gov/pubmed/19300475 http://dx.doi.org/10.1371/journal.pcbi.1000311 |
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