使用染色体深度学习模型从基因标记预测基因表达,取决于基因标记功能,调节距离和细胞状态
Alan E Murphy1,2, Aydan Askarova1,2, Boris Lenhard3
1UK Dementia Research Institute at Imperial College London, 86 Wood Lane, London W12 0BZ, UK.
Nucleic acids research
|December 11, 2024
概括
基因标记活性和基因表达是相关的,但细胞状态和基因组位置很重要. 机器学习模型现在考虑这些因素来预测转录并揭示生物学见解.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- 从基因标记中预测基因表达对于理解表观遗传学至关重要.
- 之前的机器学习模型忽略了细胞状态,基因素标记功能和远端调节元素.
- 需要更全面的模型来整合这些因素,以获得更深入的生物学洞察力.
研究的目的:
- 综合调查七种组分体标记和11种细胞类型和多种细胞状态的基因表达之间的关系.
- 开发和应用先进的深度学习模型 (卷积和基于注意力的模型) 来预测来自激素标记活动的转录,无论是在促进器和远程调节元件上.
- 通过in silico扰动测试,探索这些模型的实用性,以发现新的生物学见解,包括功能和疾病相关的位置.
主要方法:
- 利用了大规模的数据集,包括11种不同的细胞类型的7个组素标记.
- 采用卷积神经网络和基于注意力的深度学习模型来预测转录活动.
- 在近端 (促进体) 和远端调节元件中研究了基因素标记活性.
- 在体中进行的基因素标记扰动测试,以评估功能影响.
主要成果:
- 证明了基因组标记功能,基因组距离和细胞状态共同影响基因组标记和转录之间的关系.
- 发现没有一个单一的基因组标记能够在所有基因组和细胞环境中一致预测基因表达.
- 通过in silico扰动实验确定了特定的功能和与疾病相关的基因组位置.
- 建立了一个利用染色体深度学习模型产生新生物学发现的框架.
结论:
- 基因标记活性和基因表达之间的关系是复杂的,并且取决于环境,受细胞状态和基因组位置的影响.
- 从表观遗传数据中准确预测转录状态,需要考虑多个因素的整体方法.
- 深度学习模型提供了一个强大的平台,用于剖析表观遗传调节,并发现新的生物学见解,包括潜在的治疗点.
相关概念视频
02:32Histone Modification
13.0K
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...
13.0K
02:36Chromatin Immunoprecipitation- ChIP
11.1K
Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
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...
Types of ChIP
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...
11.1K
02:35Chromatin Position Affects Gene Expression
23.2K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.2K
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
8.2K
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...
8.2K
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