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PXD016730 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of Putative Early Atherosclerosis Biomarkers by Unsupervised Deconvolution of Heterogeneous Vascular Proteomes
DescriptionCoronary artery disease remains a leading cause of death in industrialized nations, and early detection of disease is a critical intervention target in order to effectively treat patients and manage risk. Proteomic analysis of mixed tissue homogenates may obscure subtle protein changes that occur uniquely in underlying tissue subtypes. The unsupervised ‘convex analysis of mixtures’ (CAM) tool has previously been shown to effectively segregate cellular subtypes from mixed expression data. In this study, we hypothesized that CAM would identify proteomic information specifically informative to early atherosclerosis lesion involvement that could lead to potential markers of early disease detection. We quantified the proteome of 99 paired Abdominal Aorta (AA) and Left Anterior Descending Coronary Artery (LAD) specimens (N=198 specimens total) acquired during autopsy of young adults free of diagnosed cardiac disease. The CAM tool was then used to segregate protein subsets uniquely associated with different underlying tissue types, yielding markers of normal and fibrous plaque (FP) tissues in LAD and AA (N=62 lesions markers). CAM-derived FP marker expression was validated against pathologist estimated luminal surface involvement of FP, as well as in an orthogonal cohort of ‘pure’ fibrous plaque, fatty streak, and normal vascular specimens. A targeted mass spectrometry (MS) analysis quantified 39 of 62 CAM-FP markers in plasma from women with angiographically verified coronary artery disease (CAD, N=46) or free from apparent CAD (control, N=40). Elastic net variable selection with logistic regression reduced this list to 10 proteins capable of classifying CAD status in this cohort with <6% misclassification error, and a mean area under the receiver operating characteristic curve of 0.992 (Confidence Interval 0.968-0.998) after cross validation. The proteomics-CAM workflow identified lesion-specific molecular biomarker candidates by distilling the most representative molecules from heterogenous tissue types.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportsupported by repository but incomplete data and/or metadata
PrimarySubmitterSarah Parker
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListPhospho; Carbamidomethyl; Oxidation; Label:13C(6)15N(2); Label:13C(6)15N(4)
InstrumentTripleTOF 6600; QTRAP 6500+
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-12-12 14:37:27ID requested
12021-01-21 11:47:18announced
Publication List
Parker SJ, Chen L, Spivia W, Saylor G, Mao C, Venkatraman V, Holewinski RJ, Mastali M, Pandey R, Athas G, Yu G, Fu Q, Troxlair D, Vander Heide R, Herrington D, Van Eyk JE, Wang Y, Identification of Putative Early Atherosclerosis Biomarkers by Unsupervised Deconvolution of Heterogeneous Vascular Proteomes. J Proteome Res, 19(7):2794-2806(2020) [pubmed]
Keyword List
submitter keyword: Atherosclerosis, Tissue Fibrous Plaque proteome
Contact List
Sarah Parker
contact affiliationCedars-Sinai Medical Center
contact emailsarah.parker@cshs.org
lab head
Sarah Parker
contact affiliationCedars-Sinai Medical Center
contact emailsarah.parker@cshs.org
dataset submitter
Full Dataset Link List
Panorama Public dataset URI