用RNA速度进行因果基因调节分析,揭示了缓慢和快速转录因子之间的相互作用
Rohit Singh1, Alexander P Wu1, Anish Mudide2
1Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
Cell systems
|May 16, 2024
概括
维洛拉玛利用单细胞表达动态推断基因调节网络 (GRNs). 这种方法揭示了转录因子 (TF) 速度与疾病的关系,将缓慢的TF与质瘤和快速的TF与神经精神疾病联系起来.
科学领域:
- 计算生物学 计算生物学
- 基因组学就是基因组学.
- 系统生物学 系统生物学
背景情况:
- 单细胞表达动态为基因调控网络 (GRNs) 提供了洞察力.
- 现有的GRN推断方法往往无法捕捉复杂的分支差异化轨迹或需要细胞的线性排序.
- 转录因子 (TFs) 在细胞过程中调节基因表达起着至关重要的作用.
研究的目的:
- 开发一种新的计算方法,Velorama,用于因果GRN推理,以适应复杂的单细胞分化动态.
- 为了能够估计TF-目标基因相互作用的速度.
- 在人类发展和疾病的背景下,研究TF相互作用速度和调节功能之间的关系.
主要方法:
- 维洛拉玛表示单细胞分化作为细胞的定向非循环图 (DAG).
- DAG是使用伪时间或RNA速度测量来构建的.
- 该方法允许估计TF对目标基因的影响速度.
主要成果:
- 维洛拉玛成功地模拟了超越线性轨迹的复杂差异化动态.
- 有证据表明,TF相互作用的速度与它们的监管作用之间存在相关性.
- 在人体皮质形成过程中,缓慢的TFs与质瘤有关,而快速的TFs与神经精神疾病有关.
结论:
- 维洛拉玛为从单细胞表达动态的因果GRN推断提供了一个强大的框架.
- TF相互作用速度是理解基因调节及其与疾病的联系的一个重要因素.
- 维洛拉玛是RNA速度工具包中一个有价值的补充,用于研究分化和疾病机制.
更多相关视频
11:00Metabolic Labeling of Newly Transcribed RNA for High Resolution Gene Expression Profiling of RNA Synthesis, Processing and Decay in Cell Culture
Published on: August 8, 2013
27.2K
07:23Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
8.5K
相关概念视频
01:23Regulation of Expression at Multiple Steps
893
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
893
02:24Regulation of Expression Occurs at Multiple Steps
22.6K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.6K
02:36RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
01:30Structure of a Gene
12.5K
A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
12.5K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
01:42What is Gene Expression?
167.4K
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
167.4K