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准确的转录因子活动推断,用MetaTF解读单细胞转录基因数据中的细胞身份

Yongfei Hu^1,2, Yuanyuan Zhu³, Guangjue Tang¹

¹Department of Bioinformatics, Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|May 21, 2025

概括

一个新的计算框架,metaTF,准确地从单细胞RNA测序 (scRNA-seq) 数据中推断出转录因子 (TF) 的活性. 这有助于更好地理解细胞的身份和功能,在复杂的生物系统,如瘤.

科学领域:

计算生物学计算生物学
基因组学就是基因组学.
癌症研究癌症研究

背景情况:

瘤中的细胞异质性会影响癌症的进展和治疗.
单细胞RNA测序 (scRNA-seq) 揭示了瘤微环境中的细胞多样性.
目前使用基因表达相似性的细胞身份表征方法可能无法捕获不同的功能角色.

研究的目的:

从scRNA-seq数据中推断转录因子 (TF) 活动的新计算框架metaTF的引入.
根据TF活动估计的现有方法来评估metaTF的绩效.
为了证明metaTF在表征细胞身份和功能在生物环境中的实用性.

主要方法:

开发metaTF,一个用于TF活动推断的计算框架.
将metaTF应用于scRNA-seq数据集,包括小鼠造血干细胞发育和乳腺癌.
对metaTF与现有的TF活动推断方法进行比较分析.

主要成果:

metaTF在估计TF活动方面表现优于现有方法.
metaTF在小鼠造血干细胞发育过程中有效地表征细胞身份.
metaTF提供了乳腺癌细胞的卓越功能特征,并确定了神经调节的T细胞的新型子集.

结论:

metaTF能够从scRNA-seq数据中进行强大的TF活动分析.
该框架显著增强了细胞身份和功能的表征.
metaTF有助于理解复杂组织中的细胞独特性和功能.

关键词:

细胞身份是细胞的身份.在 scRNA-seqq 中.转录因子活动活性.瘤免疫微环境是一个微环境.

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相关概念视频

General Transcription Factors

General Transcription Factors

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...

Transcription Factors

Transcription Factors

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...

Combinatorial Gene Control

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

Cell Specific Gene Expression

Cell Specific Gene Expression

Transcription

Transcription

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,...

Chromatin Immunoprecipitation- ChIP

Chromatin Immunoprecipitation- ChIP

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...