PXD045304

PXD045304 is an original dataset announced via ProteomeXchange.

Title	A new multiplexed plasma biomarker panel developed using targeted proteomics and machine learning has diagnostic and prognostic potential in children with hypertrophic cardiomyopathy
Description	Background Hypertrophic cardiomyopathy (HCM) is defined clinically by pathological left ventricular hypertrophy (LVH). We have previously developed a plasma proteomics biomarker panel that correlates with clinical markers of disease severity and sudden cardiac death (SCD) risk in adult patients with HCM. The aim of this study was to validate the adult biomarkers and perform new discovery proteomics in childhood-onset HCM. Methods Fifty-nine protein biomarkers were identified from an exploratory plasma proteomics screen in children with HCM and augmented into our existing multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay. The association of these biomarkers with clinical phenotypes and outcomes was prospectively tested in plasma collected from 148 children with HCM and 50 healthy controls. Machine learning techniques were used to develop novel paediatric plasma proteomic biomarker panels. Results Four previously validated adult HCM markers (Aldolase Fructose-Bisphosphate A, Complement C3a, Talin-1 and Thrombospondin 1) and three new markers (Glycogen Phosphorylase B, Lipoprotein A and Profilin 1) were elevated in paediatric HCM. Using supervised machine learning applied to training (n=137) and validation cohorts (n=61), this 7-biomarker panel differentiated HCM from healthy controls with an area under the curve of 1.0 in the training dataset (sensitivity 100% [95% confidence interval: 95–100]; specificity 100% [96–100]) and 0.82 in the validation dataset (sensitivity 75% [59–86]; specificity 88% [75–94]). Reduced circulating levels of 4 other peptides (Apolipoprotein L1-, Complement 5b-, Immunoglobulin Heavy Constant Epsilon- and Serum Amyloid A4-peptide) found in children with high SCD risk provided complete separation from the low and intermediate risk groups, and predicted mortality and adverse cardiovascular outcomes (hazard ratio 1.53 [1.2 –2.0], p = 0.001). Conclusion In children, a 7-biomarker proteomics panel can distinguish HCM from controls with high sensitivity and specificity, and a second 4-biomarker panel identifies those at high risk of adverse outcomes, including sudden cardiac death.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:48:26.593.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gabriella Captur
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q-Tof Ultima

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-12 06:06:44	ID requested
1	2024-10-08 11:19:03	announced
⏵ 2	2024-10-22 06:48:27	announced	2024-10-22: Updated project metadata.

10.1161/circgen.123.004448;

Captur G, Doykov I, Chung SC, Field E, Barnes A, Zhang E, Heenan I, Norrish G, Moon JC, Elliott PM, Heywood WE, Mills K, Kaski JP, Novel Multiplexed Plasma Biomarker Panel Has Diagnostic and Prognostic Potential in Children With Hypertrophic Cardiomyopathy. Circ Genom Precis Med, 17(3):e004448(2024) [pubmed]

submitter keyword: Childhood-onset HCM proteomics

Professor Kevin
contact affiliation	Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London, WC1N 1EH, UK
contact email	kevin.mills@ucl.ac.uk
lab head
Gabriella Captur
contact affiliation	UCL
contact email	gabriella.captur@ucl.ac.uk
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/2024/07/PXD045304

PRIDE project URI

• PRIDE
  1. PXD045304
     1. Label: PRIDE project
     2. Name: A new multiplexed plasma biomarker panel developed using targeted proteomics and machine learning has diagnostic and prognostic potential in children with hypertrophic cardiomyopathy