Tissue specific protein-protein associations prioritize candidate disease associated genes
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ABSTRACT: Proteins that interact together participate in the same cellular process and influence the same organismal traits. Despite the progress in mapping protein interactions we lack knowledge of how these change across tissues. Due to coordinated (post)transcriptional control, protein complex members have highly correlated abundances that are predictive of functional association. Here, we have compiled 7840 proteomic samples measuring protein levels in 11 human tissues and use these to define an atlas of tissue specific protein associations. This method recapitulates known protein complexes and the larger structural organization of the cell. Stable protein complexes are well preserved across tissues with signaling and metabolic interactions showing larger variation. Less than 20% of interaction changes across tissues are estimated to be due to protein expression differences with cell-type specific cellular structures, such as synaptic vesicles, being a second significant driver of differences. We further supported the brain protein association network through co-fraction experiments in synaptosomes, curation of brain derived pull-down data and AlphaFold2 models and illustrate how this network can functionally prioritize candidate genes within loci linked to brain disorders
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Rattus Norvegicus (rat)
TISSUE(S): Brain
SUBMITTER: Marc van Oostrum
LAB HEAD: Bernd Wollscheid
PROVIDER: PXD049084 | Pride | 2024-05-17
REPOSITORIES: Pride
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