期刊
JOURNAL OF PROTEOME RESEARCH
卷 20, 期 4, 页码 1972-1980出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00602
关键词
proteomics; quantification; R; peptides; bioinformatics; computation; proteoform; proteins; linear model; statistics
资金
- NIH [T15LM007359, 5T32HG002760, 5P41GM108538]
PeCorA is a strategy for detecting quantitative disagreements between peptides in shotgun proteomics, providing important insights in protein quantitation studies. It can identify regulated post-translational modifications or poorly quantified peptides, improving the accuracy of protein quantitation. By using PeCorA, potential anomalies in the proteome can be uncovered, leading to more reliable results in protein quantity analysis.
Shotgun proteomics techniques infer the presence and quantity of proteins using peptide proxies produced by cleavage of the proteome with a protease. Most protein quantitation strategies assume that multiple peptides derived from a protein will behave quantitatively similar across treatment groups, but this assumption may be false due to (1) heterogeneous proteoforms and (2) technical artifacts. Here we describe a strategy called peptide correlation analysis (PeCorA) that detects quantitative disagreements between peptides mapped to the same protein. PeCorA fits linear models to assess whether a peptide's change across treatment groups differs from all other peptides assigned to the same protein. PeCorA revealed that similar to 15% of proteins in a mouse microglia stress data set contain at least one discordant peptide. Inspection of the discordant peptides shows the utility of PeCorA for the direct and indirect detection of regulated post-translational modifications (PTMs) and also for the discovery of poorly quantified peptides. The exclusion of poorly quantified peptides before protein quantity summarization decreased falsepositives in a benchmark data set. Finally, PeCorA suggests that the inactive isoform of prothrombin, a coagulation cascade protease, is more abundant in plasma from COVID-19 patients relative to non-COVID-19 controls. PeCorA is freely available as an R package that works with arbitrary tables of quantified peptides.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据