|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Raffield, LM, Dang, H, Pratte, KA, Jacobson, S, Gillenwater, L, Ampleford, E, Barjaktarevic, I, Basta, P, Clish, CB, Comellas, AP, Cornell, E, Curtis, JL, Doerschuk, C, Durda, P, Emson, C, Freeman, C, Guo, X, Hastie, AT, Hawkins, GA, Herrera, J, W Johnson, C, Labaki, WW, Liu, Y, Masters, B, Miller, M, Ortega, VE, Papanicolaou, G, Peters, S, Taylor, KD, Rich, SS, Rotter, JI, Auer, P, Reiner, AP, Tracy, RP, Ngo, D, Gerszten, RE, O'Neal, WKay, Bowler, RP|
|Corporate Authors||NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium|
|Date Published||2020 May 09|
Novel proteomics platforms, such as the aptamer-based SOMAscan platform, can quantify large numbers of proteins efficiently and cost-effectively and are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross-assay comparisons are appropriate. We explored the correlation of results from immunoassays with relative protein quantification by SOMAscan. For 63 proteins assessed in two chronic obstructive pulmonary disease (COPD) cohorts, Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and COPDGene, using Myriad Rules Based Medicine (RBM) multiplex immunoassays and SOMAscan, Spearman correlation coefficients ranged from -0.13 to 0.97, with a median correlation coefficient of ∼0.5 and consistent results across cohorts. A similar range was observed for immunoassays in the population based Multi-Ethnic Study of Atherosclerosis (MESA) and for other assays in COPDGene and SPIROMICS. Comparisons of relative quantification from the antibody-based Olink platform and SOMAscan in a small cohort of myocardial infarction patients also showed a wide correlation range. Finally, we integrated cis pQTL data, mass spectrometry aptamer confirmation, and other publicly available data to assess relationships with observed correlations . Correlation between proteomics assays shows a wide range and should be carefully considered when comparing and meta-analyzing proteomics data across assays and studies. Significance: This paper provides information on the comparability of antibody- and aptamer-based protein measures across multiple cohort studies. As new multi-cohort and multi-platform meta-analyses and replication efforts are initiated using novel proteomics assays, our analysis suggests that investigators must more fully consider differences in protein concentration measurements obtained from different platforms and assess the level of correlation between those platforms. In addition to correlation data, metrics such as mass spectrometry-based aptamer confirmation or the presence of cis pQTLs may help infer the specificity of different proteomics platforms when results differ. This article is protected by copyright. All rights reserved.