一个可概括的Hi-C基础模型,用于跨物种的染色体架构,单细胞和多omics分析
Xiao Wang1,2, Yuanyuan Zhang3, Suhita Ray4
1Department of Genome Sciences, University of Washington, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
HiCFoundation是一个新的AI模型,它将3D基因组结构与表观基因组数据集成在一起. 它增强了Hi-C分析,揭示了细胞分化过程中的全基因组循环损失,并使单细胞分辨率成为可能.
科学领域:
- 基因组学就是基因组学.
- 计算生物学 计算生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 核DNA形成一个复杂的3D结构,影响细胞功能.
- 高通量染色体构造捕获 (Hi-C) 测量了基因组架构,而像ATAC-seq这样的表观基因组测试描述了调节.
- 整合Hi-C和表观基因组数据是具有挑战性的,因为数据属性和分析不一致.
研究的目的:
- 开发HiCFoundation,这是一个新的基础模型,用于对3D基因组结构和监管功能的综合分析.
- 改进Hi-C数据的分析,包括分辨率增强和循环检测.
- 将染色质构成与基因组功能联系起来,并使单细胞分辨率分析成为可能.
主要方法:
- 培训 HiCFoundation 在数百个测试中的数百万个 HiC 接触矩阵子矩阵上.
- 应用该模型来分析316个物种的基因组结构.
- 增强低覆盖范围的Hi-C数据以研究细胞分化.
- 从Hi-C数据预测表观基因组活动,并分析单细胞Hi-C数据.
主要成果:
- HiCFoundation在3D基因组分析任务中实现了最先进的性能.
- 该模型揭示了在造血干细胞和祖细胞分化过程中全基因组循环损失.
- 它证明了跨多种物种的概括性,并使单细胞基因组结构分析成为可能.
- HiCFoundation成功地将染色质构成与表观基因组功能联系起来.
结论:
- HiCFoundation为3D基因组架构分析提供了一个统一,高效和可解释的平台.
- 它促进了对基因组3D结构及其跨物种的调节机制的系统研究.
- 该模型推进了单细胞和多细胞分析,为基因组功能提供了新的见解.
相关概念视频
02:38Heterochromatin
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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
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01:01Euchromatin
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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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02:36Chromatin Immunoprecipitation- ChIP
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ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
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02:32Histone Modification
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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