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Fabregat, A.

Publications and source records attributed to Fabregat, A..

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ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Pathway analyses are key methods to analyse 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 Reactomes 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 thereby greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses. We used ReactomeGSA to characterise the role of B cells in anti-tumour immunity. We compared B cell rich and poor human cancer samples from five TCGA transcriptomics and two CPTAC proteomics studies. There, B cell-rich lung adenocarcinoma samples lack the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumour 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.

bioinformatics↗

PathwayMatcher: multi-omics pathway mapping and proteoform network generation

BackgroundMapping biomedical data to functional knowledge is an essential task in bioinformatics and can be achieved by querying identifiers, e.g. gene sets, in pathway knowledgebases. However, the isoform and post-translational modification states of proteins are lost when converting input and pathways into gene-centric lists.\n\nFindingsBased on the Reactome knowledgebase, we built a network of protein-protein interactions accounting for the documented isoform and modification statuses of proteins. We then implemented a command line application called PathwayMatcher (github.com/PathwayAnalysisPlatform/PathwayMatcher) to query this network. PathwayMatcher supports multiple types of omics data as input, and outputs the possibly affected biochemical reactions, subnetworks, and pathways.\n\nConclusionsPathwayMatcher enables refining the network-representation of pathways by including isoform and post-translational modifications. The specificity of pathway analyses is hence adapted to different levels of granularity and it becomes possible to distinguish interactions between different forms of the same protein.

bioinformatics↗