基因指南 (GeneCompass):通过基于知识的跨物种基础模型解读通用基因调节机制
Xiaodong Yang1,2,3, Guole Liu4,5, Guihai Feng1,6,7
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cell research
|October 7, 2024
概括
我们开发了GeneCompass,这是一款分析数百万个单细胞转录组的AI模型,以发现跨物种的通用基因调节机制. 这种方法加速了细胞命运调节器和潜在药物点的发现.
科学领域:
- 基因组学就是基因组学.
- 计算生物学 计算生物学
- 发展生物学 发展生物学
背景情况:
- 了解通用基因调节机制是生物学和医学的关键.
- 当前的研究往往忽略了跨物种和多细胞类型的整合.
- 单细胞测序和深度学习为综合分析提供了新的途径.
研究的目的:
- 开发一种跨物种基础模型来破译基因调节机制.
- 整合来自人类和小鼠的大规模单细胞转录组数据.
- 识别细胞命运转变和潜在治疗点中的关键因素.
主要方法:
- 构建了超过1.01亿个人类和小鼠单细胞转录组的数据集.
- 开发了GeneCompass,一个基于知识的跨物种基础模型.
- 利用自主监督学习和微调用于下游生物任务.
主要成果:
- GeneCompass有效地整合了生物知识,以提高基因调节的理解.
- 该模型在单个物种和跨物种分析中表现优于现有的方法.
- 确定了成功诱导人类胚胎干细胞分化成为淋巴结核命运的候选基因.
结论:
- GeneCompass利用人工智能揭示了通用的基因调节机制.
- 该模型显示了发现细胞命运调节者的巨大潜力.
- 加速了用于临床应用的新药标的识别.
相关概念视频
Combinatorial Gene Control
8.3K
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...
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...
8.3K
Evolutionary Relationships through Genome Comparisons
5.7K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
5.7K
Constitutive and Regulated Gene Expression
2
Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
2
Reporter Genes
11.3K
Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
11.3K
Regulation of Expression at Multiple Steps
875
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...
875
Cell Specific Gene Expression
13.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.5K


