Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 100142 Beijing, China.
School of Basic Medical Sciences, Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, 102206 Beijing, China.
Nucleic Acids Res. 2023 Oct 13;51(18):9552-9566. doi: 10.1093/nar/gkad720.
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/).
内在的 DNA 性质，包括弯曲，在各种生物系统中起着至关重要的作用。最近，一种名为 loop-seq 的高通量技术取得了一项进展，使得在一次实验中确定数十万条 50 碱基对 DNA 双链的柔韧性成为可能。然而，评估人类等大型基因组中的碱基分辨率序列柔韧性仍然具有挑战性，这需要数千次这样的实验。在这里，我们介绍了“BendNet”——一种深度神经网络，它可以通过使用酵母中的 loop-seq 结果作为训练数据，预测碱基分辨率的内在 DNA 弯曲度。BendNet 可以高精度地预测来自不同物种的任何给定序列的 DNA 柔韧性。为了探索 BendNet 的实用性，我们将其应用于人类基因组，并观察到 DNA 柔韧性与染色质特征和涉及转录/增强子调控、DNA 复制、转录因子结合和染色体外环状 DNA 生成的疾病风险区域相关。这些发现扩展了我们对哺乳动物中 DNA 力学及其与转录调控之间关联的理解。最后，我们通过应用 BendNet 为 307 个物种构建了基因组 DNA 柔韧性图谱的综合资源，并提供了一个在线工具来评估用户指定的 DNA 序列的柔韧性（http://www.dnabendnet.com/）。
