PXD055473-2

PXD055473 is an original dataset announced via ProteomeXchange.

Title	Untargeted proteomics enables ultra-rapid variant prioritization in mitochondrial and other rare diseases
Description	Only half of individuals with suspected rare diseases receive a definitive genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate patient care and reduces the number of potentially unnecessary interventions and related healthcare costs. Here, we demonstrate that an untargeted quantitative mass-spectrometry approach quantifying >6,000 proteins in primary fibroblasts representing >80% of known mitochondrial disease genes can provide functional evidence for 88% of individuals in a cohort of known primary mitochondrial diseases. We profiled >90 individuals, including 28 with confirmed disease and diagnosed 6 individuals with variants in both nuclear and mitochondrial genes. Lastly, we developed an ultra-rapid proteomics pipeline using minimally invasive peripheral blood mononuclear cells to support upgrade of variant pathogenicity in as little as 54 hours in critically ill infants with suspected mitochondrial disorders. This study supports the integration of a single untargeted proteomics test into routine diagnostic practice for the diagnosis of rare genetic disorders in clinically actionable timelines, offering a paradigm shift for the functional validation of genetic variants.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:57:39.672.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-02 04:24:32	ID requested
1	2024-09-02 23:02:21	announced
⏵ 2	2024-10-22 06:57:40	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, Fibroblasts, PBMCs, HEK293T, Orbitrap

David Stroud
contact affiliation	1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, 3010, Australia 2Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia 3Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, VIC, 3052, Australia
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
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/2024/09/PXD055473

PRIDE project URI

• PRIDE
  1. PXD055473
     1. Label: PRIDE project
     2. Name: Untargeted proteomics enables ultra-rapid variant prioritization in mitochondrial and other rare diseases