整合RNAseq转录组学和N-甘氨基组学揭示了生物合成途径,并预测了结构特定的N-甘氨基表达
Michael Russelle S Alvarez1, Xavier A Holmes1, Armin Oloumi1
1Department of Chemistry, University of California, Davis Davis California USA cblebrilla@ucdavis.edu.
Chemical science
|April 7, 2025
概括
机器学习模型从糖基因表达中预测蛋白质N-甘氨酸的丰富性,有助于发现癌症和自身免疫性疾病等疾病的治疗点.
科学领域:
- 糖化学和系统生物学 系统生物学
- 计算生物学 计算生物学
- 生物化学 生物化学
背景情况:
- 蛋白N-糖化在疾病发病过程中至关重要,但由于生物合成途径重叠,鉴定涉及的特定糖基因是复杂的.
- 异常的N-糖化与各种疾病有关,包括癌症,神经退行性和自身免疫性疾病,突出了对治疗点的需求.
研究的目的:
- 开发监督机器学习模型,以根据糖基因表达来预测N-甘氨酸的丰富性.
- 阐明不同细胞类型和条件的甘氨基基表达和N-甘氨酸组成之间的相互作用.
主要方法:
- 经过训练的回归模型使用配对的LC-MS/MS N-glycomic和3'-TagSeq转录组数据集.
- 利用来自多种组织来源 (B细胞,大脑,结肠,肺,肌肉,前列腺) 的数据,包括约400个N-甘氨酸化合物和>160个甘氨基基基因.
- 经验证的模型准确性 (R2 > 0.8) 和评估的葡萄糖基因重要性评分用于N-葡萄糖的预测.
主要成果:
- 准确的预测模型 (R2>0.8) 已开发用于N-甘氨酸在各种细胞类型的丰富度,包括肺癌和B细胞.
- 模型重要性得分确定了特定的甘氨基基因和N-甘氨酸类型之间的显著关联.
- 预测在不同的细胞输入量中保持一致,优于LC-MS/MS甘氨基化合物.
结论:
- 开发的机器学习模型可靠地预测N-糖化,即使细胞输入低,包括单细胞样本.
- 这些发现提供了关于细胞N-糖化机制的见解,并确定了与糖化相关疾病的潜在治疗策略.
- 这项研究为了解糖原-N-甘氨酸相互作用及其与疾病相关性提供了一个框架.
相关概念视频
RNA-seq
9.7K
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
9.7K
Ribosome Profiling
3.4K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.4K


