410V Poster Online - Virtual Posters
Tuesday June 07, 11:00 AM - 3:00 PM

Authors:
Gary Churchill ²; Tian Zhang ¹; Gregory Keele ²; Steven Munger ²; Fernando Pardo-Manuel de Villena ³; Martin Ferris ³; Joao Paulo ¹; Steven Gygi ¹

Affiliations:
1) Harvard University, Cambridge, MA; 2) The Jackson Laboratory, Bar Harbor, ME; 3) University of North Carolina at Chapel Hill, Chapel HIll, NC

Keywords:
Other (Genetic analysis of multi-omics data identifies drivers of protein phosphorylation)

Phosphorylation is a chemical process in which a phosphate group is added to an organic compound. Site-specific phosphorylation of proteins regulates many cellular processes including activation of enzymes and signaling cascades. The abundance of phosphorylated peptides can be measured by mass spectrometry and is determined by the abundance of the target protein/peptide and the proportion of target sites that are phosphorylated. We quantified the abundance of phosphorylated peptides, as well as proteins and transcripts in heart, liver, and kidney tissue samples from 116 genetically diverse female and male mice of the Collaborative Cross strain panel. We identified ~700 phosphorylation quantitative trait loci (phQTL) in the three tissues and applied genetic mediation analysis to identify causal drivers of phosphorylation. Candidate mediators included kinases, phosphatases, cytokines, and other factors with established roles as well as identifying novel interactions between target proteins and genes that regulate protein phosphorylation. Our analysis highlights multiple targets of pyruvate dehydrogenase kinase 1 (PDK1), a regulator of mitochondrial function that shows reduced activity in the NZO/HILtJ mouse, a polygenic model of obesity and type 2 diabetes.