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Identification of transcription factor high accumulation DNA zones

BACKGROUND: Transcription factors (TF) play a crucial role in the regulation of gene transcription; alterations of their activity and binding to DNA areas are strongly involved in cancer and other disease onset and development. For proper biomedical investigation, it is hence essential to correctly...

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Autores principales: Cascianelli, Silvia, Ceddia, Gaia, Marchesi, Alberto, Masseroli, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590011/
https://www.ncbi.nlm.nih.gov/pubmed/37864168
http://dx.doi.org/10.1186/s12859-023-05528-1
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author Cascianelli, Silvia
Ceddia, Gaia
Marchesi, Alberto
Masseroli, Marco
author_facet Cascianelli, Silvia
Ceddia, Gaia
Marchesi, Alberto
Masseroli, Marco
author_sort Cascianelli, Silvia
collection PubMed
description BACKGROUND: Transcription factors (TF) play a crucial role in the regulation of gene transcription; alterations of their activity and binding to DNA areas are strongly involved in cancer and other disease onset and development. For proper biomedical investigation, it is hence essential to correctly trace TF dense DNA areas, having multiple bindings of distinct factors, and select DNA high occupancy target (HOT) zones, showing the highest accumulation of such bindings. Indeed, systematic and replicable analysis of HOT zones in a large variety of cells and tissues would allow further understanding of their characteristics and could clarify their functional role. RESULTS: Here, we propose, thoroughly explain and discuss a full computational procedure to study in-depth DNA dense areas of transcription factor accumulation and identify HOT zones. This methodology, developed as a computationally efficient parametric algorithm implemented in an R/Bioconductor package, uses a systematic approach with two alternative methods to examine transcription factor bindings and provide comparative and fully-reproducible assessments. It offers different resolutions by introducing three distinct types of accumulation, which can analyze DNA from single-base to region-oriented levels, and a moving window, which can estimate the influence of the neighborhood for each DNA base under exam. CONCLUSIONS: We quantitatively assessed the full procedure by using our implemented software package, named TFHAZ, in two example applications of biological interest, proving its full reliability and relevance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-023-05528-1.
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spelling pubmed-105900112023-10-22 Identification of transcription factor high accumulation DNA zones Cascianelli, Silvia Ceddia, Gaia Marchesi, Alberto Masseroli, Marco BMC Bioinformatics Software BACKGROUND: Transcription factors (TF) play a crucial role in the regulation of gene transcription; alterations of their activity and binding to DNA areas are strongly involved in cancer and other disease onset and development. For proper biomedical investigation, it is hence essential to correctly trace TF dense DNA areas, having multiple bindings of distinct factors, and select DNA high occupancy target (HOT) zones, showing the highest accumulation of such bindings. Indeed, systematic and replicable analysis of HOT zones in a large variety of cells and tissues would allow further understanding of their characteristics and could clarify their functional role. RESULTS: Here, we propose, thoroughly explain and discuss a full computational procedure to study in-depth DNA dense areas of transcription factor accumulation and identify HOT zones. This methodology, developed as a computationally efficient parametric algorithm implemented in an R/Bioconductor package, uses a systematic approach with two alternative methods to examine transcription factor bindings and provide comparative and fully-reproducible assessments. It offers different resolutions by introducing three distinct types of accumulation, which can analyze DNA from single-base to region-oriented levels, and a moving window, which can estimate the influence of the neighborhood for each DNA base under exam. CONCLUSIONS: We quantitatively assessed the full procedure by using our implemented software package, named TFHAZ, in two example applications of biological interest, proving its full reliability and relevance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-023-05528-1. BioMed Central 2023-10-20 /pmc/articles/PMC10590011/ /pubmed/37864168 http://dx.doi.org/10.1186/s12859-023-05528-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Software
Cascianelli, Silvia
Ceddia, Gaia
Marchesi, Alberto
Masseroli, Marco
Identification of transcription factor high accumulation DNA zones
title Identification of transcription factor high accumulation DNA zones
title_full Identification of transcription factor high accumulation DNA zones
title_fullStr Identification of transcription factor high accumulation DNA zones
title_full_unstemmed Identification of transcription factor high accumulation DNA zones
title_short Identification of transcription factor high accumulation DNA zones
title_sort identification of transcription factor high accumulation dna zones
topic Software
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590011/
https://www.ncbi.nlm.nih.gov/pubmed/37864168
http://dx.doi.org/10.1186/s12859-023-05528-1
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