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MAPDP:一个基于云的免疫肽组学分析计算平台。

MAPDP: A Cloud-Based Computational Platform for Immunopeptidomics Analyses.

机构信息

Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3C 3J7, Canada.

Department of Biochemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada.

出版信息

J Proteome Res. 2020 Apr 3;19(4):1873-1881. doi: 10.1021/acs.jproteome.9b00859. Epub 2020 Mar 13.

Abstract

The immunopeptidome corresponds to the repertoire of peptides presented at the cell surface by the major histocompatibility complex (MHC) molecules. Cytotoxic T cells scan this repertoire to identify nonself antigens that can arise from tumors or infected cells. The identification of actionable antigenic targets is key to the development of therapeutic cancer vaccines, T-cell therapy, and other T-cell receptor-based biologics. The growing clinical interest for immunopeptidomics has accelerated the development of high throughput proteogenomic platforms that provide a system-level analysis of MHC-associated peptides. Improvement in sensitivity and throughput of mass spectrometers now allows the detection of a few thousands of peptides from less than 100 million cells. To manage the amount of data generated by these instruments, we have developed the MHC-associated peptide discovery platform (MAPDP), a novel open-source cloud-based computational platform for immunopeptidomic analyses. It provides convenient access from a web portal to immunopeptidomes stored in the database, filtering tools, various visualizations, annotations (e.g., IEDB, dbSNP, gnomAD), peptide-binding affinity prediction (mhcflurry, NetMHC), HLA genotyping, and the generation of personalized proteome databases. MAPDP functionalities are demonstrated here by the discovery of MHC peptides featuring new genetic variants identified in two previously published ovarian carcinoma data sets.

摘要

免疫肽组学对应于主要组织相容性复合体 (MHC) 分子在细胞表面呈现的肽谱。细胞毒性 T 细胞扫描这个肽谱,以识别来自肿瘤或感染细胞的非自身抗原。鉴定可行的抗原性靶标是开发治疗性癌症疫苗、T 细胞疗法和其他基于 T 细胞受体的生物制剂的关键。免疫肽组学的临床兴趣日益浓厚,加速了高通量蛋白质基因组学平台的发展,这些平台提供了 MHC 相关肽的系统水平分析。质谱仪的灵敏度和通量的提高现在允许从不到 1 亿个细胞中检测到几千个肽。为了管理这些仪器产生的数据量,我们开发了 MHC 相关肽发现平台 (MAPDP),这是一种用于免疫肽组学分析的新型开源基于云的计算平台。它通过 Web 门户方便地访问存储在数据库中的免疫肽组,提供过滤工具、各种可视化、注释(例如 IEDB、dbSNP、gnomAD)、肽结合亲和力预测(mhcflurry、NetMHC)、HLA 基因分型和个性化蛋白质组数据库的生成。通过在两个先前发表的卵巢癌数据集发现具有新遗传变异的 MHC 肽,展示了 MAPDP 的功能。

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