Jessica A. Lasky-Su小组在研究中取得进展。他们报道了使用纳米颗粒富集平台的质谱蛋白质组学全基因组关联研究。相关论文于2025年11月27日发表在《自然—遗传学》杂志上。

在这里，该研究组表明基于质谱（MS）的蛋白质组学可以补充这些研究，并提供对特定蛋白质异构体和表位改变变体的作用的见解。利用Seer蛋白图纳米颗粒富集质谱平台，该团队在两个队列的血浆样品中蛋白质的全基因组关联研究中鉴定并复制了新的pQTLs，并评估了先前从亲和蛋白质组学平台报道的pQTLs。该团队发现，被评估的pQTLs中有大于30%被MS蛋白质组学证实与遗传变异引起蛋白质丰度变化的假设一致，而另外30%无法被复制，可能是由于表位效应，尽管需要根据具体情况考虑不可复制的其他解释。基于质谱的血浆样本全基因组关联分析说明了不同蛋白质组学方法在鉴定蛋白质数量性状位点方面的互补性。

据介绍，迄今为止，大多数关于蛋白质数量性状位点（pQTLs）的研究都依赖于亲和蛋白质组学平台，这些平台只能提供有限的目标蛋白质亚型信息，并且可能受到其表位结合遗传变异的影响。

附：英文原文

Title: A genome-wide association study of mass spectrometry proteomics using a nanoparticle enrichment platform

Author: Suhre, Karsten, Chen, Qingwen, Halama, Anna, Mendez, Kevin, Dahlin, Amber, Stephan, Nisha, Thareja, Gaurav, Sarwath, Hina, Guturu, Harendra, Dwaraka, Varun B., Smith, Ryan, Batzoglou, Serafim, Schmidt, Frank, Lasky-Su, Jessica A.

Issue&Volume: 2025-11-27

Abstract: Most studies to date of protein quantitative trait loci (pQTLs) have relied on affinity proteomics platforms, which provide only limited information about the targeted protein isoforms and may be affected by genetic variation in their epitope binding. Here we show that mass spectrometry (MS)-based proteomics can complement these studies and provide insights into the role of specific protein isoform and epitope-altering variants. Using the Seer Proteograph nanoparticle enrichment MS platform, we identified and replicated new pQTLs in a genome-wide association study of proteins in blood plasma samples from two cohorts and evaluated previously reported pQTLs from affinity proteomics platforms. We found that >30% of the evaluated pQTLs were confirmed by MS proteomics to be consistent with the hypothesis that genetic variants induce changes in protein abundance, whereas another 30% could not be replicated and are possibly due to epitope effects, although alternative explanations for nonreplication need to be considered on a case-by-case basis. Genome-wide association analyses of blood plasma samples using a mass spectrometry-based platform illustrate the complementarity of different proteomics approaches for identifying protein quantitative trait loci.

DOI: 10.1038/s41588-025-02413-w

Source: https://www.nature.com/articles/s41588-025-02413-w