Evidence map›Paper›PMID 36944993›Full record

ArticleGenome biology2023

Multi-omics analysis identifies drivers of protein phosphorylation.

Tian Zhang, Gregory R Keele, Isabela Gerdes Gyuricza, Matthew Vincent, Catherine Brunton, Timothy A Bell, Pablo Hock, Ginger D Shaw, Steven C Munger, Fernando Pardo-Manuel de Villena and 4 more

Open access · goldFull text read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
6.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 22 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Tian Zhang *Harvard Medical School, Boston, MA, 02115, USA.
Gregory R Keele *The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Isabela Gerdes GyuriczaThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Matthew VincentThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Catherine BruntonThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Timothy A BellDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Pablo HockDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Ginger D ShawDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Steven C MungerThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Fernando Pardo-Manuel de VillenaDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Martin T FerrisDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Joao A PauloHarvard Medical School, Boston, MA, 02115, USA.
Steven P GygiHarvard Medical School, Boston, MA, 02115, USA. steven_gygi@hms.harvard.edu.
Gary A ChurchillThe Jackson Laboratory, Bar Harbor, ME, 04609, USA. gary.churchill@jax.org.ORCID 0000-0001-9190-9284
Jackson Laboratory · USUniversity of North Carolina at Chapel Hill · USHarvard University · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Anna Karolina Palucka · 1985 to 2026
$61.9M
Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, HEISE, MARK T · 2012 to 2021
$36.6M
UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Elizabeth J Mayer-Davis · 1999 to 2026
$31.6M
Systems Genetics of TuberculosisP01AI132130 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BEHAR, SAMUEL M · 2017 to 2021
$11.2M
New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
Systems Genetic Analysis of Multi-parent CrossesR01GM070683 · NIGMS · JACKSON LABORATORY · PI BROMAN, KARL W, CHURCHILL, GARY A · 2004 to 2022
$6.8M
Genetic underpinning of diabetes associated with arsenic exposureR01ES029925 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRY, REBECCA, PARDO-MANUEL DE VILLENA, FERNANDO · 2019 to 2023
$3.3M
Leveraging Natural Genetic Diversity and Systems Genetics to Elucidate the Complex Hierarchy of Gene Regulation Underlying Ground State Pluripotency, Cell Fate Decisions and Tissue HomeostasisR35GM133495 · NIGMS · JACKSON LABORATORY · PI MUNGER, STEVEN CARMEN · 2019 to 2023
$2.0M
Bayesian Modeling of Mass-Spec Proteomics Data to Advance Studies of the Genetic Regulation of ProteinsF32GM134599 · NIGMS · JACKSON LABORATORY · PI KEELE, GREGORY R · 2020 to 2021
$139k
A new multi-pathway kinase activity assay applied to compound library screening in cancer biologyK99CA273170 · NCI · HARVARD MEDICAL SCHOOL · PI ZHANG, TIAN · 2022 to 2022
$117k
NCI NIH HHS K99 CA273170NCI NIH HHS P30 CA034196NIAID NIH HHS P01 AI132130NIAID NIH HHS U19 AI100625NIDDK NIH HHS P30 DK056350NIEHS NIH HHS R01 ES029925NIGMS NIH HHS F32 GM134599NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM070683NIGMS NIH HHS R35 GM133495
6 · The paper itself

Abstract

backgroundPhosphorylation of proteins is a key step in the regulation of many cellular processes including activation of enzymes and signaling cascades. The abundance of a phosphorylated peptide (phosphopeptide) is determined by the abundance of its parent protein and the proportion of target sites that are phosphorylated.

resultsWe quantified phosphopeptides, proteins, and transcripts in heart, liver, and kidney tissue samples of mice from 58 strains of the Collaborative Cross strain panel. We mapped ~700 phosphorylation quantitative trait loci (phQTL) across the three tissues and applied genetic mediation analysis to identify causal drivers of phosphorylation. We identified kinases, phosphatases, cytokines, and other factors, including both known and potentially novel interactions between target proteins and genes that regulate site-specific 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.

conclusionsTogether, this integrative multi-omics analysis in genetically diverse CC strains provides a powerful tool to identify regulators of protein phosphorylation. The data generated in this study provides a resource for further exploration.

Indexed as

Diabetes Mellitus, Type 2AnimalsMiceMultiomicsPeptidesPhosphorylationQuantitative Trait LociPeptidesCollaborative CrossMedation analysisMulti-omicsPhosphorylationPhosphorylation regulationQuantitative trait loci (QTL)

Identifiers

PMID36944993
PMCPMC10031968
OpenAlexW4328093235

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read75
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.