Data independent acquisition mass spectrometry in severe Rheumatic Heart Disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.
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ABSTRACT: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. A machine learning (ML) approach was applied to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to AUC of the ROC for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were each higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls.
INSTRUMENT(S): TripleTOF 6600
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Cell, Blood Plasma
DISEASE(S): Thanatophoric Dysplasia,Type 2 Diabetes Mellitus,Swine Influenza,Cardiovascular System Disease,Wounds And Injuries,Stage Iv Colorectal Cancer,Chronic Bronchitis,Sjogren's Syndrome,Trypanosomiasis
SUBMITTER: jing yang
LAB HEAD: Mark Engel
PROVIDER: PXD030598 | Pride | 2022-04-04
REPOSITORIES: Pride
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