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Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations
MOTIVATION: Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031777/ https://www.ncbi.nlm.nih.gov/pubmed/31529022 http://dx.doi.org/10.1093/bioinformatics/btz709 |
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author | Zhu, Qian Tekpli, Xavier Troyanskaya, Olga G Kristensen, Vessela N |
author_facet | Zhu, Qian Tekpli, Xavier Troyanskaya, Olga G Kristensen, Vessela N |
author_sort | Zhu, Qian |
collection | PubMed |
description | MOTIVATION: Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. RESULTS: We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes. AVAILABILITY AND IMPLEMENTATION: The analysis code and data are deposited at https://bitbucket.org/qzhu/breast.cancer.tf/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. |
format | Online Article Text |
id | pubmed-7031777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70317772020-02-25 Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations Zhu, Qian Tekpli, Xavier Troyanskaya, Olga G Kristensen, Vessela N Bioinformatics Discovery Notes MOTIVATION: Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. RESULTS: We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes. AVAILABILITY AND IMPLEMENTATION: The analysis code and data are deposited at https://bitbucket.org/qzhu/breast.cancer.tf/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2020-02-15 2019-09-16 /pmc/articles/PMC7031777/ /pubmed/31529022 http://dx.doi.org/10.1093/bioinformatics/btz709 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Discovery Notes Zhu, Qian Tekpli, Xavier Troyanskaya, Olga G Kristensen, Vessela N Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title | Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title_full | Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title_fullStr | Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title_full_unstemmed | Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title_short | Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
title_sort | subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations |
topic | Discovery Notes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031777/ https://www.ncbi.nlm.nih.gov/pubmed/31529022 http://dx.doi.org/10.1093/bioinformatics/btz709 |
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