利用表观基因组和三维基因组组织来解释调控变异
Brittany Baur1, Junha Shin1, Jacob Schreiber2
1Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS computational biology
|July 10, 2023
概括
这项研究引入了L-HiC-Reg来绘制调节相互作用,并识别受遗传变异影响的基因网络. 这种方法有助于理解复杂的疾病,如精神分裂症和冠状动脉疾病.
科学领域:
- 基因组学就是基因组学.
- 系统生物学 系统生物学
- 计算生物学 计算生物学
背景情况:
- 由于未知的基因目标和细胞类型背景,了解调节变异如何影响复杂的特征是很困难的.
- 细胞类型特定的远程调节相互作用是研究这些影响的关键,但高分辨率地图很少.
- 鉴定变体准的基因子网络仍然是一个挑战.
研究的目的:
- 开发一种计算方法来预测细胞类型特定的远程调节相互作用.
- 创建一个框架来识别来自全基因组关联研究 (GWAS) 的变异向的基因网络.
- 解释与复杂的表型相关的调节性单核酸多态 (SNP).
主要方法:
- 开发了L-HiC-Reg,一种随机森林回归模型,用于预测各种细胞类型的高分辨率接触数.
- 集成的L-HiC-Reg预测与基于网络的框架来识别变异向基因网络.
- 将该方法应用于路线图表表观遗传学绘图联盟的55种细胞类型,并分析了GWAS数据.
主要成果:
- 成功预测了55种细胞类型的调控相互作用,使调控SNP的解释成为可能.
- 描述了十五种复杂的表型,包括精神分裂症,冠状动脉疾病 (CAD) 和克罗恩病.
- 鉴定了差异连接的基因子网络,揭示了调控性SNP的已知和新型基因目标.
结论:
- 开发的L-HiC-Reg方法和网络分析管道为研究监管变化的特定环境影响提供了强大的框架.
- 这种方法通过将调节变异与特定的基因网络联系起来,提高了对复杂疾病遗传结构的理解.
- 这项研究提供了有价值的相互作用汇总和分析管道,用于监管基因组学和复杂特征遗传学的未来研究.
相关概念视频
01:46Epigenetic Regulation
31.1K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.1K
03:17Inheritance of Chromatin Structures
6.3K
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...
6.3K
02:35Chromatin Position Affects Gene Expression
23.4K
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...
23.4K
02:32Position-effect Variegation
6.4K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.4K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.1K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.1K
02:02Cis-regulatory Sequences
9.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K