通过使用深度学习来预测基因组修饰的A/B区块
Suchen Zheng1, Nitya Thakkar1, Hannah L Harris2
1Department of Computer Science, Brown University, Providence, RI, USA.
iScience
|April 22, 2024
概括
研究人员开发了CoRNN,这是一种新的工具,可以通过基因组修改来预测基因组分离. 这种方法克服了Hi-C数据的高成本,使细胞类型特定的3D基因组组织研究成为可能.
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:
- 三维基因组组织,特别是染色质分为活性 (A) 和非活性 (B) 的细分,对细胞功能至关重要.
- 研究细胞类型特定的基因组组织受到 Hi-C 数据生成的高成本和复杂性的阻碍.
研究的目的:
- 开发一种具有成本效益的计算工具,用于预测基因组细分.
- 为了能够对细胞类型特定的3D基因组组织进行大规模分析.
主要方法:
- 开发一个称为CoRNN.的循环神经网络 (RNN) 模型.
- 使用基因组修饰丰富数据作为CoRNN的输入.
- 使用跨细胞类型分析和独立数据集验证CoRNN的预测性能.
主要成果:
- CoRNN准确地预测了不同细胞类型的A/B区,平均AuROC为90.9%.
- 鉴定出H3K27ac和H3K36me3等基因组标记是隔间状态的强有力的预测因素.
- 错误的预测在模糊的分类区域中被发现,这表明需要进一步调查的领域.
- 该模型通过成功预测独立组织样本中的隔间来证明了可通用性.
结论:
- CoRNN提供了一种强大且易于使用的方法来预测3D基因组组织.
- 该工具可以在没有昂贵的实验数据的情况下研究细胞类型特定的基因组活动.
- CoRNN在独立样本上的验证强调了它在基因组研究中的广泛适用性.
相关概念视频
02:38Heterochromatin
12.5K
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...
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...
12.5K
02:32Histone Modification
13.3K
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...
13.3K
01:01Euchromatin
6.9K
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...
6.9K
01:32Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
02:25Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
03:17Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K