The SysteMHC Atlas v2.0, an updated resource for mass spectrometry-based immunopeptidomics

The SysteMHC Atlas v1.0 was the first public repository dedicated to mass spectrometry-based immunopeptidomics. Here we introduce a newly released version of the SysteMHC Atlas v2.0 (https://systemhc.sjtu.edu.cn), a comprehensive collection of 7190 MS files from 303 allotypes. We extended and optimized a computational pipeline that allows the identification of MHC-bound peptides carrying on unexpected post-translational modifications (PTMs), thereby resulting in 471K modified peptides identified over 60 distinct PTM types. In total, we identified approximately 1.0 million and 1.1 million unique peptides for MHC class I and class II immunopeptidomes, respectively, indicating a 6.8-fold increase and a 28-fold increase to those in v1.0. The SysteMHC Atlas v2.0 introduces several new features, including the inclusion of non-UniProt peptides, and the incorporation of several novel computational tools for FDR estimation, binding affinity prediction and motif deconvolution. Additionally, we enhanced the user interface, upgraded website framework, and provided external links to other resources related. Finally, we built and provided various spectral libraries as community resources for data mining and future immunopeptidomic and proteomic analysis. We believe that the SysteMHC Atlas v2.0 is a unique resource to provide key insights to the immunology and proteomics community and will accelerate the development of vaccines and immunotherapies. Graphical Abstract