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bioRxiv · 10.1101/2023.12.30.573715

MetalinksDB: a flexible and contextualizable resource of metabolite-protein interactions

Farr, E. B.·Dimitrov, D.·Turei, D.·Schmidt, C.·Lobentanzer, S.·Dugourd, A.·Saez-Rodriguez, J.
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Abstract

Interactions between proteins and metabolites are key for cellular function, from the catalytic breakdown of nutrients to signaling. An important case is cell-cell communication, where cellular metabolites are secreted into the microenvironment and initiate a signaling cascade by binding to an intra- or extracellular receptor of another cell. While protein-protein mediated cell-cell communication is routinely inferred from transcriptomic data, for metabolite-protein interactions this is challenging due to the limitations of high-throughput single-cell and spatial metabolomics technologies, together with the absence of comprehensive prior knowledge resources that include metabolites. Here we report MetalinksDB, a comprehensive and flexible database of intercellular metabolite-protein interactions that is a magnitude larger than existing ones. MetalinksDB can be tailored to specific biological contexts such as diseases, pathways, or tissue/cellular locations by querying subsets of interactions using the web interface (https://metalinks.omnipathdb.org/) or the knowledge graph adapters. We showcase the use of MetalinksDB by identifying deregulated processes in renal cancer patients from multi-omics data as well as inferring metabolite-mediated cell-cell communication events driving acute kidney injury from spatial transcriptomic data. We anticipate that MetalinksDB will facilitate the study of metabolite-mediated communication processes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/573715v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@18c78aaorg.highwire.dtl.DTLVardef@145f21borg.highwire.dtl.DTLVardef@119d16borg.highwire.dtl.DTLVardef@3febb_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Farr, E. B., Dimitrov, D., Turei, D., Schmidt, C., Lobentanzer, S., Dugourd, A., Saez-Rodriguez, J.. 2023-12-30. MetalinksDB: a flexible and contextualizable resource of metabolite-protein interactions. https://doi.org/10.1101/2023.12.30.573715

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