Assessing base-resolution DNA mechanics on the genome scale

Abstract 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 ch...

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Bibliographic Details
Published in:Nucleic acids research 2023-10, Vol.51 (18), p.9552-9566
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Chromatin - chemistry
Chromatin - genetics
Chromatin - metabolism
Computational Biology
DNA - chemistry
DNA - genetics
DNA - metabolism
Genome, Human
Genomics - methods
Humans
Neural Networks, Computer
Nucleic Acid Conformation
Sequence Analysis, DNA - methods
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Summary:Abstract 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/). Graphical Abstract Graphical Abstract
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkad720