MAPDP: A Cloud-Based Computational Platform for Immunopeptidomics Analyses

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.

免疫肽库对应于由主要组织相容性复合物（MHC）分子在细胞表面展示的肽库。细胞毒性T细胞扫描此肽库以识别源自肿瘤或感染细胞的非己抗原。识别可操作的抗原靶点是开发治疗性癌症疫苗、T细胞疗法以及其他基于T细胞受体的生物制剂的关键。随着对免疫肽组学的临床兴趣日益增长，高通量蛋白质组学平台的发展也得到加速，这些平台提供了MHC相关肽的系统级分析。质谱仪灵敏度和通量的提升，现在使得从不到一亿个细胞中检测到数千个肽成为可能。为了管理这些仪器产生的大量数据，我们开发了MHC相关肽发现平台（MAPDP），这是一个新颖的开源云计算平台，用于免疫肽组学分析。它通过网络门户提供便捷的访问，包括存储在数据库中的免疫肽库、过滤工具、多种可视化、注释（例如，IEDB、dbSNP、gnomAD）、肽结合亲和力预测（mhcflurry、NetMHC）、HLA基因分型以及个性化蛋白质组库的生成。本文通过发现MHC肽中包含在两个先前发表的卵巢癌数据集中识别出的新遗传变异，展示了MAPDP的功能。