PXD011007

PXD011007 is an original dataset announced via ProteomeXchange.

Title	Proteomics exploration of the Atp7b-/- mouse plasma proteome: translational relevance for the diagnosis of Wilson’s disease
Description	Wilson’s disease (WD) is a rare genetic disease caused by mutations in the ATP7B gene. These mutations impact the expression and/or function of the copper-transporting ATP7B protein, leading to massive toxic accumulation of copper in the liver and brain. Due to its low incidence and highly variable clinical presentations, WD is challenging to diagnose. Here, we explored the plasma proteome of the Atp7b-/- mouse, a genetic and phenotypic model of WD, to provide new insights into the pathogenic mechanisms of WD and discover potential biomarkers for WD diagnosis. A mass spectrometry (MS)-based proteomics workflow combining unbiased discovery analysis followed by targeted quantification was developed. Analysis of two independent groups of samples (discovery and validation cohorts) highlighted seven plasma proteins for which abundance was significantly modified (more than 2-fold) between Atp7b-/- mice and wild-type littermates. To assess the clinical significance and specificity of these seven proteins as potential biomarkers for WD, we adapted our targeted proteomics assay to allow the quantification of human orthologues in plasma from WD patients (treated with copper chelators), non-alcoholic steatohepatitis patients (disease-control group), and healthy donors. The plasma proteome changes observed in the Atp7b-/- mouse were not confirmed in treated WD patients, with the exception of alpha-1 antichymotrypsin, levels of which were decreased in WD patients compared to healthy individuals. Plasma ceruloplasmin was investigated in both the Atp7b-/- mouse model and human patients, and was found to be significantly decreased in the human form of WD only.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:02.250.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yohann Couté
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q TRAP; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-05 05:20:14	ID requested
1	2020-04-14 02:06:33	announced
⏵ 2	2024-10-22 05:02:10	announced	2024-10-22: Updated project metadata.

Lacombe M, Jaquinod M, Belmudes L, Cout, é Y, Ramus C, Combes F, Burger T, Mintz E, Barthelon J, Leroy V, Poujois A, Lachaux A, Woimant F, Brun V, mouse plasma proteome. Metallomics, 12(2):249-258(2020) [pubmed]

10.1039/c9mt00225a;

submitter keyword: LC-SRM, liver, biomarkers,Wilson's disease, nanoLC-MS/MS

Virginie Brun
contact affiliation	EDyP
contact email	virginie.brun@cea.fr
lab head
Yohann Couté
contact affiliation	EDyP
contact email	yohann.coute@cea.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011007
     1. Label: PRIDE project
     2. Name: Proteomics exploration of the Atp7b-/- mouse plasma proteome: translational relevance for the diagnosis of Wilson’s disease