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.

免疫肽组（immunopeptidome）指由主要组织相容性复合体（MHC）分子呈递于细胞表面的全套肽段库。细胞毒性T细胞会扫描该肽段库，以识别源自肿瘤或受感染细胞的非己抗原。鉴定临床可用的抗原靶点，是开发治疗性癌症疫苗、T细胞疗法及其他基于T细胞受体的生物制剂的关键所在。当前临床对免疫肽组学的关注度与日俱增，推动了高通量蛋白质基因组学平台的发展，这类平台可实现MHC相关肽段的系统级分析。随着质谱仪的灵敏度与通量不断提升，如今已可从不足1亿个细胞中检测到数千种肽段。为高效管理此类仪器产生的海量数据，我们开发了MHC相关肽发现平台（MAPDP）——一款用于免疫肽组学分析的新型基于云的开源计算平台。该平台可通过网络门户便捷访问数据库中存储的免疫肽组，提供过滤工具、多种可视化功能、多源注释信息（如IEDB、dbSNP、gnomAD数据库）、肽结合亲和力预测（mhcflurry、NetMHC）、HLA基因分型，以及个性化蛋白质组数据库的生成功能。本文通过在两份已发表的卵巢癌数据集中鉴定携带新型遗传变异的MHC肽段，验证了MAPDP的各项功能。