PXD051750

PXD051750 is an original dataset announced via ProteomeXchange.

Title	Integrative Gene Regulatory Network Analysis Discloses Key Driver Genes of Fibromuscular Dysplasia in Females: the DEFINE-FMD study
Description	Fibromuscular dysplasia (FMD) is a poorly understood but relatively common vascular disease affecting 3-5% of adult females. The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm which can lead to hypertension, stroke, heart attack and even death. While a limited number of gene variants have been associated with FMD, there are no animal models and few insights as to why this disease occurs. By integrating DNA genotype and RNA sequence data from primary fibroblasts of 83 FMD patients and 71 matched healthy controls from the DEFINE-FMD study, we inferred 18 gene co-expression networks, four of which were found to act together as an FMD-associated supernetwork in the arterial wall. After in vivo perturbation of this gene co-expression supernetwork by selective knockout of a top network key driver, mice developed arterial dilation; a hallmark of FMD. Molecular studies indicated that this supernetwork governs multiple aspects of vascular cell physiology and functionality, including collagen/matrix production. Using linkage disequilibrium score regression to determine the genetic contribution to disease, we found that this supernetwork accounts for a significant proportion of FMD heritability (H squared). These studies illuminate the complex causal mechanisms of FMD and suggest a potential therapeutic avenue to address this challenging disease.
HostingRepository	PRIDE
AnnounceDate	2024-05-01
AnnouncementXML	Submission_2024-05-01_02:13:27.244.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051750
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	XIAOKE YIN
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; 1x(18)O labeled deamidated L-asparagine; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-25 16:38:08	ID requested
⏵ 1	2024-05-01 02:13:27	announced

10.6019/PXD051750;

submitter keyword: Aorta, FMD,Mouse, Label-free quantification

Manuel Mayr
contact affiliation	National Heart and Lung Institute, Imperial College London, United Kingdom
contact email	m.mayr@imperial.ac.uk
lab head
XIAOKE YIN
contact affiliation	National Heart and Lung Institute, Faculty of Medicine, Imperial College London
contact email	xiaoke.yin@imperial.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051750
     1. Label: PRIDE project
     2. Name: Integrative Gene Regulatory Network Analysis Discloses Key Driver Genes of Fibromuscular Dysplasia in Females: the DEFINE-FMD study