The SysteMHC Atlas project

Abstract

Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts.

The HLA Ligand Atlas - A resource of natural HLA ligands presented on benign tissues

“…to 195,507 for HLA-II, as currently encompassed in SysteMHC (Shao et al, 2018) and IEDB (Vita et al, 2015) ( Figure 1B).…”

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA

“…The main challenge for a targeted pHLA therapeutic is achieving sufficient specificity in the context of a vast landscape of potential self-antigens. For instance, even on individual cell types, data from our in-house mass spectrometry database and published direct evidence demonstrate that the number of unique peptides can be in the range of tens of thousands (39)(40)(41)(42). Considering the full human protein-coding genome, the number of peptides presented has been estimated to be over 11 million (43).…”

Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry

“…13,16,74,76,77 Additional software for upstream and downstream processing of data is available and search engines can be integrated into larger platforms, such as OpenMS 78 and the Trans Peptidomic Pipeline (TPP), 76 allowing the design of complex workflows. Due to different results obtained from database search employing various algorithms, MS data can be uploaded directly into the SysteMHC Atlas project 79 and the PRoteomics IDentifications (PRIDE) database. 80 Generally, proteomic workflows both for MS analysis and automated sequence identification have been adapted to the field of HLA peptidomics, often at the expense of HLA ligands.…”