Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, 
integrating data from different 'omics technologies and different species still 
requires considerable bioinformatics knowledge.Here we present the novel 
ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. 
ReactomeGSA can be used through Reactome's existing web interface and the novel 
ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. 
Data from different species is automatically mapped to a common pathway space. 
Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly 
integrated in the analysis. ReactomeGSA greatly reduces the technical barrier 
for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA 
to characterize the role of B cells in anti-tumor immunity. We compared B cell 
rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) 
transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium 
(CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the 
otherwise present activation through NFkappaB. This may be linked to the 
presence of a specific subset of tumor associated IgG+ plasma cells that lack 
NFkappaB activation in scRNA-seq data from human melanoma. This showcases how 
ReactomeGSA can derive novel biomedical insights by integrating large 
multi-omics datasets.