PXD009063

PXD009063 is an original dataset announced via ProteomeXchange.

Title	Multi-OMICS data of a Hyper IgD Syndrome family
Description	The aim of this study was to understand why two siblings carrying both the same homozygous causal mutation for the auto-inflammatory disease hyper IgD show opposite phenotypes, i.e. the first being asymptomatic, the second presenting all classical characteristics of the disease. As compared to studies of a single omics type, the multi-omics approach becomes a method of choice to resolve complex traits. Here we combined exome, proteome and transcriptome analysis in the two siblings and identified a single gene - STAT1 - harboring a rare missense variant and showing mRNA and protein abundances significantly more important in the symptomatic than the asymptomatic sister. This mutation was shown to be a gain of function mutation involved in an increased activation of the JAK/STAT pathway which is known to play a critical role in inflammatory diseases and for which specific bio-therapies exist. Pathway analysis based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling. In addition, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identifications. In conclusion, this study demonstrates the power of a multi-omics approach to uncover potentially clinically actionable targets for a personalized therapy.
HostingRepository	PRIDE
AnnounceDate	2019-10-24
AnnouncementXML	Submission_2019-10-25_03:56:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009063
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Carapito Christine
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-28 02:51:01	ID requested
1	2019-10-24 03:04:14	announced
⏵ 2	2019-10-25 03:56:04	announced	2019-10-25: Updated publication reference for PubMed record(s): 30030262.

Carapito R, Carapito C, Morlon A, Paul N, Vaca Jacome AS, Alsaleh G, Rolli V, Tahar O, Aouadi I, Rompais M, Delalande F, Pichot A, Georgel P, Messer L, Sibilia J, Cianferani S, Van Dorsselaer A, Bahram S, as a potential modifier gene in mevalonate kinase deficiency. Ann Rheum Dis, 77(11):1675-1687(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Proteogenomics analysis - Differential Analysis - Hyper IgD Syndrome - Single Amino Acid Variant Characterization

Christine CARAPITO
contact affiliation	Laboratoire de Spectrométrie de Masse BioOrganique, University of Strasbourg, CNRS, IPHC, UMR 7178, F-67000 Strasbourg, France
contact email	ccarapito@unistra.fr
lab head
Carapito Christine
contact affiliation	Department of Analytical Sciences
contact email	ccarapito@unistra.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/10/PXD009063

PRIDE project URI

• PRIDE
  1. PXD009063
     1. Label: PRIDE project
     2. Name: Multi-OMICS data of a Hyper IgD Syndrome family