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通过靶向数据库搜索方法增强基于质谱的MHC-I肽段鉴定

Enhancing Mass Spectrometry-Based MHC-I Peptide Identification Through a Targeted Database Search Approach.

作者信息

Konda Prathyusha, Murphy J Patrick, Nielsen Morten, Gujar Shashi

机构信息

Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.

Department of Pathology, Dalhousie University, Halifax, NS, Canada.

出版信息

Methods Mol Biol. 2019;2024:301-307. doi: 10.1007/978-1-4939-9597-4_19.

DOI:10.1007/978-1-4939-9597-4_19
PMID:31364058
Abstract

MHC-bound peptide ligands dictate the activation and specificity of CD8+ T- cells-based and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these peptides, wherein MS/MS spectra are compared against a reference proteome. Unfortunately, matching immunopeptide MS/MS to reference proteome databases is hindered by inflated search spaces attributed to the number of matches that need to be considered due to a lack of enzyme restriction. These large search spaces limit the efficiency with which MHC-I peptides are identified. Here we offer a solution to this problem whereby we describe a targeted database search approach and accompanying tool SpectMHC that is based on a priori predicted MHC-I peptides (Murphy et al., J Proteome Res 16:1806-1816, 2017).

摘要

与主要组织相容性复合体(MHC)结合的肽配体决定了基于CD8 + T细胞的激活和特异性,因此对于设计T细胞免疫疗法很重要。近年来,质谱(MS)技术的进步使得能够精确鉴定这些肽,即将MS / MS谱与参考蛋白质组进行比较。不幸的是,由于缺乏酶切限制而需要考虑的匹配数量导致搜索空间膨胀,这阻碍了免疫肽MS / MS与参考蛋白质组数据库的匹配。这些巨大的搜索空间限制了MHC-I肽的鉴定效率。在此,我们提供了一个解决此问题的方案,即描述一种基于先验预测的MHC-I肽的靶向数据库搜索方法及配套工具SpectMHC(Murphy等人,《蛋白质组研究杂志》16:1806 - 1816,2017)。

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