跨人体细胞类型转录的基础模型
Xi Fu1,2, Shentong Mo3,4, Alejandro Buendia5
1Program of Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY, USA. xf2217@cumc.columbia.edu.
Nature
|January 8, 2025
概括
一个新的计算模型,通用表达变换器 (GET),只使用序列和染色质可访问性数据,准确地预测人类不同细胞类型的基因表达. 这一突破增强了对基因调控和转录因子相互作用的理解.
科学领域:
- 基因组学
- 计算生物学
- 分子生物学
背景情况:
- 转录调节对于生物过程至关重要,但当前的计算模型在细胞类型和条件中难以概括.
- 准确预测基因表达需要理解调节序列和蛋白质之间的复杂相互作用.
研究的目的:
- 介绍GET (通用表达转换器),这是一个可解释的基础模型,用于在人类细胞类型中发现调节语法.
- 开发一个可通用的计算模型来预测基因表达和推断调节网络.
主要方法:
- 使用染色体可访问性数据和序列信息作为GET模型的输入.
- 在 213 种人类胎儿和成人细胞类型中训练和评估 GET,评估其在预测基因表达,调节活性和转录因子相互作用方面的表现.
- 使用基于lentivirus的大规模并行报告测试,将GET的性能与现有模型进行比较.
主要成果:
- 在预测基因表达方面,即使在新型细胞中,GET也取得了实验级准确性.
- 在不同测序平台和测试中表现出适应性.
- 鉴定了先前模型遗漏的远端调节区域,并发现了新的转录因子相互作用,包括与白血病风险相关的相互作用.
结论:
- GET为转录提供了一个可通用和准确的基础模型,其性能优于当前的方法.
- 该模型可以创建基因调节和转录因子相互作用的细胞类型特定目录.
- 在不同的生物环境中研究基因调节的能力得到了提升.
相关概念视频
General Transcription Factors
5.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.2K
Transcription Factors
75.6K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.6K
Transcription
19.7K
Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
19.7K
Transcription Elongation Factors
10.7K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
10.7K
Eukaryotic Transcription Activators
10.9K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
10.9K
Transcription Initiation
16.2K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.2K


