麻省理工学院和哈佛大学的布罗德研究所Catherine J. Wu小组近日取得一项新成果。经过不懈努力，他们探明了通过用户定义的肽库实现对癌症抗原的敏感检测。2026年2月9日出版的《自然—生物技术》发表了这项成果。

研究人员引入Pepyrus，它在大肠杆菌中产生热定义的、个体特异性或疾病特异性的肽文库，以提高MS肽鉴定的敏感性和信誉度，包括低丰度的新抗原。使用Pepyrus生成的肽库与HLA特异性数据无关的获取策略配对，课题组人员在每次注射中恢复了75%的预期序列，并鉴定出0.1复杂背景下的Fmol刺入肽。小组使用Pepyrus来创建个性化文库，促进临床相关HLA肽的鉴定，包括从黑色素瘤和肾细胞癌患者的细胞系中提取的几种新肽。Pepyrus能够识别罕见的HLA结合肽，并提供生成大型训练数据集的能力，以改进光谱，保留时间和离子迁移率预测工具。

研究人员表示，人类白细胞抗原（HLA）结合的肿瘤肽可以常规地从癌症样本中分离出来并进行主题质谱（MS）鉴定。然而，质谱方法可能是随机的或依赖于谱库，这些谱库通常不适用于个体特异性肽，它们限制了发现新肽的能力。

附：英文原文

Title: Sensitive detection of cancer antigens enabled by user-defined peptide libraries

Author: Manakongtreecheep, Kasidet, Ctortecka, Claudia, Correa-Medero, Luis O., Zhu, Timothy, Lippincott, Isabelle, Lawrence, Griffin M., Howard, Alexis, Hernandez, Gabrielle M., Forman, Cleo, Duggan, Emma C., Wilbrink, Marta A., Verzani, Eva K., Afeyan, Alexander B., Li, Jiaxun, Nesvizhskii, Alexey I., Oliveira, Giacomo, Keskin, Derin B., Ott, Patrick A., Clauser, Karl R., Bakalar, Matthew, Sarkizova, Siranush, Hacohen, Nir, Carr, Steven A., Abelin, Jennifer G., Wu, Catherine J.

Issue&Volume: 2026-02-09

Abstract: Human leukocyte antigen (HLA)-bound tumor peptides can be routinely isolated from cancer samples and identified using mass spectrometry (MS). However, MS approaches can be stochastic or rely on spectral libraries, which are not customarily available for individual-specific peptides, thus limiting the ability to discover novel peptides. Here, we introduce Pepyrus, which generates user-defined, individual-specific or disease-specific peptide libraries in Escherichia coli to improve the sensitivity and confidence of MS peptide identification, including lowly abundant neoantigens. Using Pepyrus-generated peptide libraries paired with an HLA-specific data-independent acquisition strategy, we recover >75% of the expected sequences per single injection for libraries of >10,000 peptides and identify 0.1fmol of spiked-in peptides in a complex background. We apply Pepyrus to create personalized libraries, facilitating identification of clinically relevant HLA peptides, including several novel peptides from cell lines derived from persons with melanoma and renal cell carcinoma. Pepyrus enables identification of rare HLA-bound peptides and provides the ability to generate large training datasets to improve spectra, retention time and ion mobility prediction tools.

DOI: 10.1038/s41587-026-03003-9

Source: https://www.nature.com/articles/s41587-026-03003-9