MassIVE MSV000090110

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Sample multiplexing-based targeted pathway proteomics with real-time analytics reveals the impact of genetic variation on protein expression

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Description

Targeted proteomics enables hypothesis-driven research by measuring the cellular expression of protein cohorts related by function, disease, or class after perturbation. Here, we present a pathway-centric approach and an assay builder resource for targeting entire pathways of proteins selected from up to 10,000 expressed proteins to directly measure their abundances, exploiting sample multiplexing to increase throughput by 16-fold. The strategy, termed GoDig, requires only a single-shot LC-MS analysis, ~1 ug combined peptide material, and real-time analytics to trigger simultaneous quantification of up to 16 samples for hundreds of analytes. We applied GoDig to quantify the impact of genetic variation on protein expression in mice fed a high-fat diet. Protein abundances were quantified for multiple protein families (e.g., kinases, lipid metabolism- and lipid droplet-associated proteins) across 480 fully-genotyped Diversity Outbred mice, revealing previously unknown protein quantitative trait loci and establishing potential linkages between specific proteins and lipid homeostasis. [doi:10.25345/C57H1DR40] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TMT ; targeted proteomics ; pQTL ; mouse proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Steven P Gygi, Department of Cell Biology, Harvard Medical School, Boston, USA, N/A
Submitting User: qingyu0126

Publications

Yu Q, Liu X, Keller MP, Navarrete-Perea J, Zhang T, Fu S, Vaites LP, Shuken SR, Schmid E, Keele GR, Li J, Huttlin EL, Rashan EH, Simcox J, Churchill GA, Schweppe DK, Attie AD, Paulo JA, Gygi SP.
Sample multiplexing-based targeted pathway proteomics with real-time analytics reveals the impact of genetic variation on protein expression.
Nat Commun. 2023 Feb 2;14(1):555. Epub 2023 Feb 2.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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