MetalinksDB: a flexible and contextualizable resource of metabolite-protein interactions
From the catalytic breakdown of nutrients to signaling, interactions between metabolites and proteins play an essential role in cellular function. An important case is cell-cell communication, where metabolites, secreted into the microenvironment, initiate signaling cascades by binding to intra- or...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 2024
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| In: |
Briefings in bioinformatics
Year: 2024, Volume: 25, Issue: 4, Pages: bbae347$p1-12 |
| ISSN: | 1477-4054 |
| DOI: | 10.1093/bib/bbae347 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1093/bib/bbae347
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| Author Notes: | Elias Farr, Daniel Dimitrov, Christina Schmidt, Denes Turei, Sebastian Lobentanzer, Aurelien Dugourd, Julio Saez-Rodriguez |
| Summary: | From the catalytic breakdown of nutrients to signaling, interactions between metabolites and proteins play an essential role in cellular function. An important case is cell-cell communication, where metabolites, secreted into the microenvironment, initiate signaling cascades by binding to intra- or extracellular receptors of neighboring cells. Protein-protein cell-cell communication interactions are routinely predicted from transcriptomic data. However, inferring metabolite-mediated intercellular signaling remains challenging, partially due to the limited size of intercellular prior knowledge resources focused on metabolites. Here, we leverage knowledge-graph infrastructure to integrate generalistic metabolite-protein with curated metabolite-receptor resources to create MetalinksDB. MetalinksDB is an order of magnitude larger than existing metabolite-receptor resources and can be tailored to specific biological contexts, such as diseases, pathways, or tissue/cellular locations. We demonstrate MetalinksDB’s utility in identifying deregulated processes in renal cancer using multi-omics bulk data. Furthermore, we infer metabolite-driven intercellular signaling in acute kidney injury using spatial transcriptomics data. MetalinksDB is a comprehensive and customizable database of intercellular metabolite-protein interactions, accessible via a web interface (https://metalinks.omnipathdb.org/) and programmatically as a knowledge graph (https://github.com/biocypher/metalinks). We anticipate that by enabling diverse analyses tailored to specific biological contexts, MetalinksDB will facilitate the discovery of disease-relevant metabolite-mediated intercellular signaling processes. |
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| Item Description: | Veröffentlicht: 22. Juli 2024 Gesehen am 28.04.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1477-4054 |
| DOI: | 10.1093/bib/bbae347 |