误解变体cysteinome的多原子分层
Heta Desai1,2, Samuel Ofori1, Lisa Boatner1,3
1Biological Chemistry Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
bioRxiv : the preprint server for biology
|August 30, 2023
概括
遗传变异经常导致癌症基因组中获得的囊蛋白,影响驱动突变和精确疗法. 我们的研究表明,这些氨酸是常见的和可用药物的点,为治疗提供了新的途径.
科学领域:
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
- 癌症生物学 癌症生物学
背景情况:
- 癌症基因组含有众多的遗传变异,错误的突变经常导致获得最常见的改变氨基酸 - - 氨酸.
- 这些获得的氨酸具有重要意义,因为它们可以充当驱动突变,并代表精确癌症治疗的标.
- 尽管它们的流行程度和治疗潜力很高,但大多数获得的半氨酸的功能作用和特征在很大程度上仍未得到研究.
研究的目的:
- 用一种新的化学蛋白质基因组学方法来描述癌症和健康基因组中氨酸获取的情况.
- 为了识别由遗传变异引起的功能性,氧化还原敏感性和潜在的可药物治疗的氨酸残留物.
- 探索获得的半氨酸的治疗含义,并制定蛋白型特异性药物发现策略.
主要方法:
- 囊蛋白化学蛋白质组学与整个外体和RNA测序数据的整合.
- 开发一个化学蛋白质基因组学平台,包括定制的2阶段错误发现率 (FDR) 控制的蛋白质基因搜索和FragPipe接口.
- 利用CADD预测来评估导致囊获取的变异的有害性.
主要成果:
- 囊的获取是癌症和健康基因组中遗传变异的常见结果,特别是当DNA修复受到损害时.
- 该研究确定了116个细胞系中11个细胞系中116个cysteine获取的实例,其中10个残留物被电友药物样分子结合.
- 发现了大量的参考囊素 (791) 接近误解变异,这表明开发蛋白形特异性化学探针的潜力.
结论:
- 化学蛋白质基因组学是一个强大的平台,用于揭示由遗传变异驱动的氨酸获取的功能格局.
- 获得的半氨酸代表了潜在的药物点和用于精确癌症治疗的可用药物的丰富来源.
- 这种方法有望推进蛋白形特异性生物学,并指导新型治疗策略的开发.
更多相关视频
07:15Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
11.0K
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.8K
相关概念视频
Cystic Fibrosis: Pathogenesis
278
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
278
Single Nucleotide Polymorphisms-SNPs
15.2K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.2K
Pleiotropy
40.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.6K
Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K
