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pmid:36980219
Proteomic Analysis in Valvular Cardiomyopathy: Aortic Regurgitation vs. Aortic Stenosis.
Theresa Holst · Johannes Petersen · Sabine Ameling · Lisa Müller · Torsten Christ · Naomi Gedeon · Thomas Eschenhagen · Hermann Reichenspurner · Elke Hammer · Evaldas Girdauskas
Cells · 2023 doi:10.3390/cells12060878
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Experiment
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Data
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Analysis
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Complete file
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We aimed to disclose specific LV myocardial protein signatures possibly contributing to differential disease progression. Global protein profiling of LV myocardial samples excised from the subaortic interventricular septum in patients with isolated AR or AS undergoing AV surgery was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry. Based on label-free quantitation protein intensities, a logistic regression model was calculated and adjusted for age, sex and protein concentration. Web-based functional enrichment analyses of phenotype-associated proteins were performed utilizing g:Profiler and STRING. Data are available via ProteomeXchange with identifier PXD039662. Lysates from 38 patients, including 25 AR and 13 AS samples, were analyzed. AR patients presented with significantly larger LV diameters and volumes (end-diastolic diameter: 61 (12) vs. 48 (13) mm, p < 0.001; end-diastolic volume: 180.0 (74.6) vs. 92.3 (78.4), p = 0.001). A total of 171 proteins were associated with patient phenotype: 117 were positively associated with AR and the enrichment of intracellular compartment proteins (i.e., assigned to carbohydrate and nucleotide metabolism, protein biosynthesis and the proteasome) was detected. Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed. In summary, functional enrichment analysis revealed specific AR- and AS-associated signatures of LV myocardial proteins.", "claims": [{"id": "claim-method", "statement": "Consideration of age, sex and protein concentration as covariates led to a stepwise reduction in data variance. 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Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 171 LV myocardial proteins were associated with the AR or AS patient phenotype.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36980219"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The mass spectrometry proteomics data have been deposited to the ProteomeXcha", "hromatography-electrospray ionization-tandem mass spectrometry. Based on label-free quantitation protein in", "hromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS, for details, see Supplementar"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Consideration of age, sex and protein concentration as covariates led to a stepwise reduction in data variance. 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