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ZSeeker:一种用于在基因组序列中检测Z-DNA的优化算法。

ZSeeker: an optimized algorithm for Z-DNA detection in genomic sequences.

作者信息

Wang Guliang, Mouratidis Ioannis, Provatas Kimonas, Chantzi Nikol, Patsakis Michail, Georgakopoulos-Soares Ilias, Vasquez Karen M

机构信息

Division of Pharmacology and Toxicology, Dell Pediatric Research Institute, College of Pharmacy, The University of Texas at Austin, 1400 Barbara Jordan Boulevard, Austin, TX 78723, United States.

Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States.

出版信息

Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf240.

DOI:10.1093/bib/bbaf240
PMID:40445004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12123511/
Abstract

Z-deoxyribonucleic acid (Z-DNA) is an alternative left-handed DNA structure with a zigzag-shaped backbone that differs from the right-handed canonical B-DNA helix. Z-DNA has been implicated in various biological processes, including transcription, replication, and DNA repair, and can induce genetic instability. Repetitive sequences of alternating purines and pyrimidines have the potential to adopt Z-DNA structures. ZSeeker is a novel computational tool developed for the accurate detection of potential Z-DNA-forming sequences in genomes, addressing key limitations of prior methods, such as computational inefficiency, difficult interpretability and usability, and lack of experimentally generated data. By introducing a novel methodology informed and validated by experimental data, ZSeeker enables the refined detection of potential Z-DNA-forming sequences. Built both as a standalone Python package and as an accessible web interface, ZSeeker allows users to input genomic sequences, adjust detection parameters, and view potential Z-DNA sequence distributions and Z-scores via downloadable visualizations. Our web platform provides a no-code solution for Z-DNA identification, with a focus on accessibility, user-friendliness, speed, and customizability. By providing efficient, high-throughput analysis, and enhanced detection accuracy, ZSeeker has the potential to support significant advancements in understanding the roles of Z-DNA in normal cellular functions, genetic instability, and its implications in human diseases.

摘要

Z-脱氧核糖核酸(Z-DNA)是一种另类的左手螺旋DNA结构,其主链呈锯齿状,不同于右手螺旋的经典B-DNA。Z-DNA参与了包括转录、复制和DNA修复在内的多种生物学过程,并可导致遗传不稳定。嘌呤和嘧啶交替出现的重复序列有可能形成Z-DNA结构。ZSeeker是一种新开发的计算工具,用于准确检测基因组中潜在的Z-DNA形成序列,解决了先前方法的关键局限性,如计算效率低、难以解释和使用,以及缺乏实验生成的数据。通过引入一种由实验数据提供信息并验证的新方法,ZSeeker能够精确检测潜在的Z-DNA形成序列。ZSeeker既作为一个独立的Python包构建,也作为一个易于访问的网络界面,允许用户输入基因组序列、调整检测参数,并通过可下载的可视化结果查看潜在的Z-DNA序列分布和Z分数。我们的网络平台为Z-DNA识别提供了一种无需编码的解决方案,重点在于可访问性、用户友好性、速度和可定制性。通过提供高效、高通量的分析以及更高的检测准确性,ZSeeker有潜力支持在理解Z-DNA在正常细胞功能、遗传不稳定中的作用及其对人类疾病的影响方面取得重大进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/5929e9a6dfa3/bbaf240f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/025d1d734696/bbaf240f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/fd93c94f04ce/bbaf240f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/39866369294a/bbaf240f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/5929e9a6dfa3/bbaf240f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/025d1d734696/bbaf240f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/fd93c94f04ce/bbaf240f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/39866369294a/bbaf240f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a1/12123511/5929e9a6dfa3/bbaf240f4.jpg

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1
ZSeeker: an optimized algorithm for Z-DNA detection in genomic sequences.ZSeeker:一种用于在基因组序列中检测Z-DNA的优化算法。
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ZSeeker: An optimized algorithm for Z-DNA detection in genomic sequences.ZSeeker:一种用于在基因组序列中检测Z-DNA的优化算法。
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本文引用的文献

1
Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease.Z 型翻转变体揭示了 Z-DNA 和 Z-RNA 在健康和疾病中的多种作用。
Life Sci Alliance. 2023 May 10;6(7). doi: 10.26508/lsa.202301962. Print 2023 Jul.
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Dynamic alternative DNA structures in biology and disease.生物学和疾病中的动态替代性DNA结构。
Nat Rev Genet. 2023 Apr;24(4):211-234. doi: 10.1038/s41576-022-00539-9. Epub 2022 Oct 31.
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High-throughput techniques enable advances in the roles of DNA and RNA secondary structures in transcriptional and post-transcriptional gene regulation.
高通量技术使得 DNA 和 RNA 二级结构在转录和转录后基因调控中的作用得到了进一步的发展。
Genome Biol. 2022 Jul 18;23(1):159. doi: 10.1186/s13059-022-02727-6.
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DNA Bending Force Facilitates Z-DNA Formation under Physiological Salt Conditions.DNA 弯曲力有助于生理盐条件下 Z-DNA 的形成。
J Am Chem Soc. 2022 Jul 27;144(29):13137-13145. doi: 10.1021/jacs.2c02466. Epub 2022 Jul 15.
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High-throughput characterization of the role of non-B DNA motifs on promoter function.非B DNA基序对启动子功能作用的高通量表征
Cell Genom. 2022 Apr 13;2(4). doi: 10.1016/j.xgen.2022.100111. Epub 2022 Mar 15.
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The complete sequence of a human genome.人类基因组的完整序列。
Science. 2022 Apr;376(6588):44-53. doi: 10.1126/science.abj6987. Epub 2022 Mar 31.
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Deep learning approach for predicting functional Z-DNA regions using omics data.深度学习方法,利用组学数据预测功能 Z-DNA 区域。
Sci Rep. 2020 Nov 5;10(1):19134. doi: 10.1038/s41598-020-76203-1.
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A predictable conserved DNA base composition signature defines human core DNA replication origins.可预测的保守 DNA 碱基组成特征定义了人类核心 DNA 复制起点。
Nat Commun. 2020 Sep 21;11(1):4826. doi: 10.1038/s41467-020-18527-0.
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ALU non-B-DNA conformations, flipons, binary codes and evolution.ALU非B-DNA构象、翻转子、二进制编码与进化
R Soc Open Sci. 2020 Jun 3;7(6):200222. doi: 10.1098/rsos.200222. eCollection 2020 Jun.
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Kethoxal-assisted single-stranded DNA sequencing captures global transcription dynamics and enhancer activity in situ.Kethoxal 辅助的单链 DNA 测序原位捕获全局转录动力学和增强子活性。
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