GQ-DNABERT揭示了与组织特异性转录相关的GQ近位增强剂-促进剂相互作用
Dmitry Konovalov1, Dmitry Umerenkov2, Alan Herbert1,3
1International Laboratory of Bioinformatics, Institute of Artificial Intelligence and Digital Sciences, Faculty of Computer Science, National Research University Higher School of Economics, Moscow 101000, Russia.
Nucleic acids research
|October 16, 2025
概括
研究人员开发了GQ-DNABERT,这是一个大型语言模型,用于识别DNA中的G四重复 (GQ). 该工具有助于理解基因调节,并协调基因组过程中的实验数据.
科学领域:
- 基因组学和分子生物学
- 生物信息学和计算生物学
- 表观遗传学和基因调控
背景情况:
- 替代DNA构造,如G-四重复 (GQs),涉及到各种基因组过程,包括转录,DNA修复和应激反应.
- 现有的用于检测GQ的实验方法产生了可变的结果,突出了对标准化,全面数据集的需求.
- 飞,特定的DNA序列,被认为通过替代DNA构造来调节基因组功能.
研究的目的:
- 开发一种强大的计算工具,用于识别人类基因组中的G-四复合体 (GQs).
- 利用一个全面的GQ数据集来训练一个大型的语言模型来预测新的GQ事件.
- 研究预测GQs在基因调节中的作用,特别是增强剂-促进剂相互作用及其与基因表达的关联.
主要方法:
- 训练了一个大型语言模型,GQ-DNABERT,使用EndoQuad,一个全面的人类GQ数据集.
- 预测了跨基因和内基因区域的 de novo GQ,评估了与 cis 调节元素 (cCREs) 和 ATAC-seq 峰值的丰富.
- 使用正常和癌细胞的多omics数据 (scATAC-seq,scRNA-seq) 评估了GQ-DNABERT预测的近位增强剂-促进剂 (pEP) 对.
主要成果:
- GQ-DNABERT成功地回忆了培训数据,并预测了新的GQ,特别是在监管区域.
- 预测的GQ pEP对与基因表达有相关性,这表明它们可能作为组织特异性调节开关发挥作用.
- 与癌细胞中的GQ pEP对相关的基因与正常组织相比,在不同的生物过程中表现出丰富.
结论:
- GQ-DNABERT是扩展和协调ex vivo基因组数据的宝贵工具,特别是用于GQ识别.
- 该模型促进了对转录调节的研究,包括在单细胞实验环境中.
- 与GQ相关的调节元素可能在正常与癌症状态下在基因表达和细胞过程中发挥不同的作用.
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