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DNAcycP:一种用于 DNA 环化能力预测的深度学习工具。

DNAcycP: a deep learning tool for DNA cyclizability prediction.

机构信息

Department of Statistics, Northwestern University, 633 Clark Street, Evanston, IL 60208, USA.

NSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, IL 60208, USA.

出版信息

Nucleic Acids Res. 2022 Apr 8;50(6):3142-3154. doi: 10.1093/nar/gkac162.

Abstract

DNA mechanical properties play a critical role in every aspect of DNA-dependent biological processes. Recently a high throughput assay named loop-seq has been developed to quantify the intrinsic bendability of a massive number of DNA fragments simultaneously. Using the loop-seq data, we develop a software tool, DNAcycP, based on a deep-learning approach for intrinsic DNA cyclizability prediction. We demonstrate DNAcycP predicts intrinsic DNA cyclizability with high fidelity compared to the experimental data. Using an independent dataset from in vitro selection for enrichment of loopable sequences, we further verified the predicted cyclizability score, termed C-score, can well distinguish DNA fragments with different loopability. We applied DNAcycP to multiple species and compared the C-scores with available high-resolution chemical nucleosome maps. Our analyses showed that both yeast and mouse genomes share a conserved feature of high DNA bendability spanning nucleosome dyads. Additionally, we extended our analysis to transcription factor binding sites and surprisingly found that the cyclizability is substantially elevated at CTCF binding sites in the mouse genome. We further demonstrate this distinct mechanical property is conserved across mammalian species and is inherent to CTCF binding DNA motif.

摘要

DNA 的机械性质在依赖 DNA 的生物过程的各个方面都起着至关重要的作用。最近,开发了一种称为 loop-seq 的高通量测定法,可以同时定量大量 DNA 片段的固有柔韧性。使用 loop-seq 数据,我们基于深度学习方法开发了一个名为 DNAcycP 的软件工具,用于预测内在的 DNA 环化能力。与实验数据相比,我们证明 DNAcycP 可以高度准确地预测内在的 DNA 环化能力。使用来自体外选择的富集可环化序列的独立数据集,我们进一步验证了预测的环化能力得分(称为 C 分数)可以很好地区分具有不同环化能力的 DNA 片段。我们将 DNAcycP 应用于多种物种,并将 C 分数与可用的高分辨率化学核小体图谱进行比较。我们的分析表明,酵母和小鼠基因组都具有跨越核小体二联体的高 DNA 弯曲性的保守特征。此外,我们将分析扩展到转录因子结合位点,令人惊讶的是,在小鼠基因组中 CTCF 结合位点处的环化能力显著升高。我们进一步证明,这种独特的力学特性在哺乳动物物种中是保守的,并且是 CTCF 结合 DNA 基序所固有的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9bd/8989542/f48c4e027b8d/gkac162fig1.jpg

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