Comparison of proteomic methods in evaluating biomarker-AKI associations in cardiac surgery patients
Year: 2021
Type: article
Abstract: Although immunoassays are the most widely used protein measurement method, aptamer-based methods such as the SomaScan platform can quantify up to 7000 proteins per biosample, creating new opportunities for unbiased discovery. However, there is limited research comparing the consistency of biomarker-disease associations between immunoassay and aptamer-based platforms. In a substudy of the TRIBE-AKI cohort, preoperative and postoperative plasma samples from 294 patients with previous immunoassay measurements were analyzed using the SomaScan platform. Inter-platform Spearman correlations ( r s ) and biomarker-AKI associations were compared across 30 preoperative and 34 postoperative immunoassay-aptamer pairs. Possible factors contributing to inter-platform differences were examined including target protein characteristics, immunoassay, and SomaScan coefficients of variation, other assay characteristics, and sample storage time. The median r s was 0.54 (interquartile range [IQR] 0.34-0.83) in postoperative samples and 0.41 (IQR 0.21-0.69) in preoperative samples. We observed a trend of greater r s in biomarkers with greater concentrations; the Spearman correlation between the concentration of protein and the inter-platform correlation was 0.64 in preoperative pairs and 0.53 in postoperative pairs. Of proteins measured by immunoassays, we observed significant biomarker-AKI associations for 13 proteins preop and 24 postop; of all corresponding aptamers, 8 proteins preop and 12 postop. All proteins significantly associated with AKI as measured by SomaScan were also significantly associated with AKI as measured by immunoassay. All biomarker-AKI odds ratios were significantly different ( P < 0.05) between platforms in 14% of aptamer-immunoassay pairs, none of which had high ( r s > 0.50) inter-platform correlations. Although similar biomarker-disease associations were observed overall, biomarkers with high physiological concentrations tended to have the highest-confidence inter-platform operability in correlations and biomarker-disease associations. Aptamer assays provide excellent precision and an unprecedented coverage and promise for disease associations but interpretation of results should keep in mind a broad range of correlations with immunoassays.
Source: Translational research
Institutions: Johns Hopkins University, Johns Hopkins Medicine, Boston University, San Francisco General Hospital, University of California, San Francisco, Brigham and Women's Hospital, Harvard University, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
Funders: U.S. Department of Health and Human Services, School of Medicine, Boston University, Evans Medical Foundation, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1044130170, G1056354480, G1735617348, G1851406594, G2348517056, G2653473004, G278200998, G2849954055, G3405256882, Proteomic Pathway Discovery in Cardiovascular Disease, G3819938352, G4034409254, G4514711904, G472208673, G4844544999, G4976486911, G5164707915, G5249188777, G5883648766, G6593263942, G6761056355, THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195, G738790256, G7441165371, G756854901, G7892070945, G7945866738, G8683204365, G9000064662, G9000135092, G9000146555, G9000162214, G9000181078, G9000239950, G9000262527, G9000354129, Yale Clinical and Translational Science Award, G942473857
OpenAlex ID: W3187584935