PXD009859 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Development a of novel targeted proteomic plasma biomarker panel for hypertrophic cardiomyopathy |
Description | Rationale There is a need for new and better biomarkers for hypertrophic cardiomyopathy (HCM) which correlate more closely with disease progression as determined by clinical imaging and biohumoral information. We have used a combination of heart tissue and plasma proteomics to identify potential biomarkers for HCM and developed them into an exploratory targeted proteomic assay. Objective To identify informative staging biomarkers for HCM and develop them into a blood test. The test using 10 µl of plasma, was developed into a 10 min liquid chromatography-tandem/mass spectrometry (LC-MS/MS) assay to analyze multiple candidate biomarkers and evaluate their association with clinical phenotypes in patients with HCM. Methods and Results Myocardial tissue and plasma samples from patients with HCM and healthy volunteers (controls) were screened using a combined gel- and nano-LC quadrupole time of flight MS approach. Twenty-six potential biomarkers were identified from the proteomics screens and developed into a multiplexed targeted proteomic assay. Their association with clinical phenotypes was tested in plasma samples collected from 207 prospectively recruited participants: 110 patients with HCM (50.1 ± 15.0 years, 70% male; 48 [44%] with identified genetic mutations) and 97 controls (49.6 ± 13.4 years, 58% male), randomly split into training (80 HCM, 67 controls) and validation datasets (30 HCM, 30 controls). Six markers (Aldolase Fructose-Bisphosphate A, Complement C3, Glutathione S-Transferase Omega 1, Ras Suppressor Protein 1, Talin 1, and Thrombospondin 1) were significantly increased (P<0.006) in the plasma of HCM patients compared to controls in the training dataset. These markers correlated with left ventricular (LV) wall thickness, LV mass and % myocardial scar on cardiovascular magnetic resonance imaging. Using supervized machine learning (ML) this panel differentiated HCM from controls (area under the curve: 0.89 in the training dataset, sensitivity 96%, 95% confidence interval [CI] 77–93; specificity 87%, 95%CI 77–94; and 0.87 in the validation dataset, sensitivity 97%, 95%CI 83–100; specificity 77%, 95%CI 58–90). Four of the biomarkers as well as the composite ML score of the plasma proteome correlated with the presence of nonsustained ventricular tachycardia and the estimated 5-year risk of sudden cardiac death. Conclusion By developing a high-throughput, multiplex, and targeted proteomic plasma assay we identified 6 biomarkers that correlate with the presence of disease and with clinical risk score for sudden cardiac death. |
HostingRepository | PRIDE |
AnnounceDate | 2019-07-08 |
AnnouncementXML | Submission_2019-07-08_01:58:02.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Gaby Captur |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | 6410 Triple Quadrupole LC/MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-05-22 07:25:25 | ID requested | |
1 | 2019-07-08 01:48:28 | announced | |
⏵ 2 | 2019-07-08 01:58:04 | announced | Updated publication reference for PubMed record(s): 31243064. |
Publication List
Captur G, Heywood WE, Coats C, Rosmini S, Patel V, Lopes LR, Collis R, Patel N, Syrris P, Bassett P, O'Brien B, Moon JC, Elliott PM, Mills K, Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine Learning. Mol Cell Proteomics, 19(1):114-127(2020) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human, Heart, Plasma, LC-MSMS, Hypertrophic Cardiomyopathy |
Contact List
Dr Kevin Mills |
contact affiliation | Lab Head, iGOSH (Centre for Inborn Errors of Metabolism) UCL Institute of Child Health at Great Ormond Street Hospital University College London 30 Guilford Street London WC1N 1EH Tel +44(0)207 905 2873 Fax +44(0)207 905 6191 |
contact email | kevin.mills@ucl.ac.uk |
lab head | |
Gaby Captur |
contact affiliation | UCL |
contact email | gabriella.captur.11@ucl.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009859
- Label: PRIDE project
- Name: Development a of novel targeted proteomic plasma biomarker panel for hypertrophic cardiomyopathy