iGTP:学习可解释的细胞嵌入,以推断单细胞转录组的基础生物机制
medRxiv : the preprint server for health sciences
|December 9, 2024
概括
一个新的可解释的生成转录程序 (iGTP) 框架模型转录程序和单细胞RNA测序数据的蛋白质-蛋白质相互作用. iGTP增强了对细胞反应的理解,并预测了对干扰的反应.
科学领域:
- 计算生物学 计算生物学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 变异自编码器 (VAE) 为单细胞转录组提供低维表示,但往往缺乏生物解释性.
- 现有的深度学习模型很难将转录程序 (TP) 和蛋白质-蛋白质相互作用 (PPI) 等生物结构集成到潜伏空间中.
研究的目的:
- 开发一个新的可解释的生成转录程序 (iGTP) 框架.
- 模拟TP空间和PPI在生物状态中的重要性.
- 提高单细胞数据分析的生物解释性和下游任务性能.
主要方法:
- 设计了iGTP框架,集成TP和PPI信息.
- 利用基因本体学,法典途径和PPI数据库用于生物背景.
- 集成的潜层与图形神经网络用于扰乱响应推断.
- 应用iGTP嵌入与细胞状态生成的潜在扩散模型.
主要成果:
- iGTP阐明了基底真理细胞反应,并在功能丰富方面表现优于现有的方法.
- 该框架成功地推断出细胞对干扰的反应.
- 使用iGTPTPTP嵌入和潜伏扩散模型,为特定细胞类型和状态生成准确的细胞嵌入.
结论:
- 对于单细胞转录组学,IGTP在PPI和TP两级提供了洞察力.
- 该框架显示了预测对新扰应答的巨大潜力.
- iGTP提高了生物研究中的深度学习模型的可解释性和实用性.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Cell Specific Gene Expression
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...
Reporter Genes
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.
Commonly used reporter...
Commonly used reporter...
Cell Specific Gene Expression
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...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...


