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Assessing base-resolution DNA mechanics on the genome scale

Intrinsic DNA properties including bending play a crucial role in diverse biological systems. A recent advance in a high-throughput technology called loop-seq makes it possible to determine the bendability of hundred thousand 50-bp DNA duplexes in one experiment. However, it's still challenging...

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Autores principales: Jiang, Wen-Jie, Hu, Congcong, Lai, Futing, Pang, Weixiong, Yi, Xinyao, Xu, Qianyi, Wang, Haojie, Zhou, Jialu, Zhu, Hanwen, Zhong, Chunge, Kuang, Zeyu, Fan, Ruiqi, Shen, Jing, Zhou, Xiaorui, Wang, Yu-Juan, Wong, Catherine C L, Zheng, Xiaoqi, Wu, Hua-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570052/
https://www.ncbi.nlm.nih.gov/pubmed/37697433
http://dx.doi.org/10.1093/nar/gkad720
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author Jiang, Wen-Jie
Hu, Congcong
Lai, Futing
Pang, Weixiong
Yi, Xinyao
Xu, Qianyi
Wang, Haojie
Zhou, Jialu
Zhu, Hanwen
Zhong, Chunge
Kuang, Zeyu
Fan, Ruiqi
Shen, Jing
Zhou, Xiaorui
Wang, Yu-Juan
Wong, Catherine C L
Zheng, Xiaoqi
Wu, Hua-Jun
author_facet Jiang, Wen-Jie
Hu, Congcong
Lai, Futing
Pang, Weixiong
Yi, Xinyao
Xu, Qianyi
Wang, Haojie
Zhou, Jialu
Zhu, Hanwen
Zhong, Chunge
Kuang, Zeyu
Fan, Ruiqi
Shen, Jing
Zhou, Xiaorui
Wang, Yu-Juan
Wong, Catherine C L
Zheng, Xiaoqi
Wu, Hua-Jun
author_sort Jiang, Wen-Jie
collection PubMed
description Intrinsic DNA properties including bending play a crucial role in diverse biological systems. A recent advance in a high-throughput technology called loop-seq makes it possible to determine the bendability of hundred thousand 50-bp DNA duplexes in one experiment. However, it's still challenging to assess base-resolution sequence bendability in large genomes such as human, which requires thousands of such experiments. Here, we introduce ‘BendNet’—a deep neural network to predict the intrinsic DNA bending at base-resolution by using loop-seq results in yeast as training data. BendNet can predict the DNA bendability of any given sequence from different species with high accuracy. To explore the utility of BendNet, we applied it to the human genome and observed DNA bendability is associated with chromatin features and disease risk regions involving transcription/enhancer regulation, DNA replication, transcription factor binding and extrachromosomal circular DNA generation. These findings expand our understanding on DNA mechanics and its association with transcription regulation in mammals. Lastly, we built a comprehensive resource of genomic DNA bendability profiles for 307 species by applying BendNet, and provided an online tool to assess the bendability of user-specified DNA sequences (http://www.dnabendnet.com/).
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spelling pubmed-105700522023-10-14 Assessing base-resolution DNA mechanics on the genome scale Jiang, Wen-Jie Hu, Congcong Lai, Futing Pang, Weixiong Yi, Xinyao Xu, Qianyi Wang, Haojie Zhou, Jialu Zhu, Hanwen Zhong, Chunge Kuang, Zeyu Fan, Ruiqi Shen, Jing Zhou, Xiaorui Wang, Yu-Juan Wong, Catherine C L Zheng, Xiaoqi Wu, Hua-Jun Nucleic Acids Res Computational Biology Intrinsic DNA properties including bending play a crucial role in diverse biological systems. A recent advance in a high-throughput technology called loop-seq makes it possible to determine the bendability of hundred thousand 50-bp DNA duplexes in one experiment. However, it's still challenging to assess base-resolution sequence bendability in large genomes such as human, which requires thousands of such experiments. Here, we introduce ‘BendNet’—a deep neural network to predict the intrinsic DNA bending at base-resolution by using loop-seq results in yeast as training data. BendNet can predict the DNA bendability of any given sequence from different species with high accuracy. To explore the utility of BendNet, we applied it to the human genome and observed DNA bendability is associated with chromatin features and disease risk regions involving transcription/enhancer regulation, DNA replication, transcription factor binding and extrachromosomal circular DNA generation. These findings expand our understanding on DNA mechanics and its association with transcription regulation in mammals. Lastly, we built a comprehensive resource of genomic DNA bendability profiles for 307 species by applying BendNet, and provided an online tool to assess the bendability of user-specified DNA sequences (http://www.dnabendnet.com/). Oxford University Press 2023-09-11 /pmc/articles/PMC10570052/ /pubmed/37697433 http://dx.doi.org/10.1093/nar/gkad720 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Computational Biology
Jiang, Wen-Jie
Hu, Congcong
Lai, Futing
Pang, Weixiong
Yi, Xinyao
Xu, Qianyi
Wang, Haojie
Zhou, Jialu
Zhu, Hanwen
Zhong, Chunge
Kuang, Zeyu
Fan, Ruiqi
Shen, Jing
Zhou, Xiaorui
Wang, Yu-Juan
Wong, Catherine C L
Zheng, Xiaoqi
Wu, Hua-Jun
Assessing base-resolution DNA mechanics on the genome scale
title Assessing base-resolution DNA mechanics on the genome scale
title_full Assessing base-resolution DNA mechanics on the genome scale
title_fullStr Assessing base-resolution DNA mechanics on the genome scale
title_full_unstemmed Assessing base-resolution DNA mechanics on the genome scale
title_short Assessing base-resolution DNA mechanics on the genome scale
title_sort assessing base-resolution dna mechanics on the genome scale
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570052/
https://www.ncbi.nlm.nih.gov/pubmed/37697433
http://dx.doi.org/10.1093/nar/gkad720
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