Dataset Information

Multi-OMICS data of a Hyper IgD Syndrome family

ABSTRACT: 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.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Q Fever

SUBMITTER: Carapito Christine

LAB HEAD: Christine CARAPITO

PROVIDER: PXD009063 | Pride | 2019-10-24

REPOSITORIES: Pride

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Publications

Multi-OMICS analyses unveil <i>STAT1</i> as a potential modifier gene in mevalonate kinase deficiency.

Carapito Raphael R Carapito Christine C Morlon Aurore A Paul Nicodème N Vaca Jacome Alvaro Sebastian AS Alsaleh Ghada G Rolli Véronique V Tahar Ouria O Aouadi Ismail I Rompais Magali M Delalande François F Pichot Angélique A Georgel Philippe P Messer Laurent L Sibilia Jean J Cianferani Sarah S Van Dorsselaer Alain A Bahram Seiamak S

Annals of the rheumatic diseases 20180720 11

<h4>Objectives</h4>The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.<h4>Methods</h4>Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, alth ...[more]

PMID: 30030262

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			Action	DRS
	MaXis.pride.mgf.gz	Mgf
	MaXis.pride.mztab.gz	Mztab
	MaXis.xml.gz	Xml
	TT423AVJ.wiff	Wiff
	TT423AVJ.wiff.scan	Wiff