Dataset Information

Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods.

ABSTRACT: High-throughput proteomic profiling using antibody or aptamer-based affinity reagents is used increasingly in human studies. However, direct analyses to address the relative strengths and weaknesses of these platforms are lacking. We assessed findings from the SomaScan1.3K (N = 1301 reagents), the SomaScan5K platform (N = 4979 reagents), and the Olink Explore (N = 1472 reagents) profiling techniques in 568 adults from the Jackson Heart Study and 219 participants in the HERITAGE Family Study across four performance domains: precision, accuracy, analytic breadth, and phenotypic associations leveraging detailed clinical phenotyping and genetic data. Across these studies, we show evidence supporting more reliable protein target specificity and a higher number of phenotypic associations for the Olink platform, while the Soma platforms benefit from greater measurement precision and analytic breadth across the proteome.

SUBMITTER: Katz DH

PROVIDER: S-EPMC9390994 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods.

Katz Daniel H DH Robbins Jeremy M JM Deng Shuliang S Tahir Usman A UA Bick Alexander G AG Pampana Akhil A Yu Zhi Z Ngo Debby D Benson Mark D MD Chen Zsu-Zsu ZZ Cruz Daniel E DE Shen Dongxiao D Gao Yan Y Bouchard Claude C Sarzynski Mark A MA Correa Adolfo A Natarajan Pradeep P Wilson James G JG Gerszten Robert E RE

Science advances 20220819 33

High-throughput proteomic profiling using antibody or aptamer-based affinity reagents is used increasingly in human studies. However, direct analyses to address the relative strengths and weaknesses of these platforms are lacking. We assessed findings from the SomaScan1.3K (N = 1301 reagents), the SomaScan5K platform (N = 4979 reagents), and the Olink Explore (N = 1472 reagents) profiling techniques in 568 adults from the Jackson Heart Study and 219 participants in the HERIT ...[more]

PMID: 35984888

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Project description:BackgroundWe used a large-scale, high-throughput DNA aptamer-based discovery proteomic platform to identify circulating biomarkers of cardiac remodeling and incident heart failure (HF) in community-dwelling individuals.MethodsWe evaluated 1895 FHS (Framingham Heart Study) participants (age 55±10 years, 54% women) who underwent proteomic profiling and echocardiography. Plasma levels of 1305 proteins were related to echocardiographic traits and to incident HF using multivariable regression. Statistically significant protein-HF associations were replicated in the HUNT (Nord-Trøndelag Health) study (n=2497, age 63±10 years, 43% women), and results were meta-analyzed. Genetic variants associated with circulating protein levels (pQTLs) were related to echocardiographic traits in the EchoGen (n=30 201) and to incident HF in the CHARGE (n=20 926) consortia.ResultsSeventeen proteins associated with echocardiographic traits in cross-sectional analyses (false discovery rate <0.10), and 8 of these proteins had pQTLs associated with echocardiographic traits in EchoGen (P<0.0007). In Cox models adjusted for clinical risk factors, 29 proteins demonstrated associations with incident HF in FHS (174 HF events, mean follow-up 19 [limits, 0.2-23.7] years). In meta-analyses of FHS and HUNT, 6 of these proteins were associated with incident HF (P<3.8×10-5; 3 with higher risk: NT-proBNP [N-terminal proB-type natriuretic peptide], TSP2 [thrombospondin-2], MBL [mannose-binding lectin]; and 3 with lower risk: ErbB1 [epidermal growth factor receptor], GDF-11/8 [growth differentiation factor-11/8], and RGMC [hemojuvelin]). For 5 of the 6 proteins, pQTLs were associated with echocardiographic traits (P<0.0006) in EchoGen, and for RGMC, a protein quantitative trait loci was associated with incident HF (P=0.001).ConclusionsA large-scale proteomics approach identified new predictors of cardiac remodeling and incident HF. Future studies are warranted to elucidate how biological pathways represented by these proteins may mediate cardiac remodeling and HF risk and to assess if these proteins can improve HF risk prediction.

Project description:BackgroundResilience is the capacity of an animal to be minimally affected by disturbances or to rapidly return to its initial state before exposure to a disturbance. Resilient livestock are desired because of their improved health and increased economic profit. Genetic improvement of resilience may also lead to trade-offs with production traits. Recently, resilience indicators based on longitudinal data have been suggested, but they need further evaluation to determine whether they are indeed predictive of improved resilience, such as disease resilience. This study investigated different resilience indicators based on deviations between expected and observed egg production (EP) by exploring their genetic parameters, their possible trade-offs with production traits, and their relationships with antibody traits in chickens.MethodsEgg production in a nucleus breeding herd environment based on 1-week-, 2-week-, or 3-week-intervals of two purebred chicken lines, a white egg-laying (33,825 chickens) and a brown egg-laying line (34,397 chickens), were used to determine deviations between observed EP and expected average batch EP, and between observed EP and expected individual EP. These deviations were used to calculate three types of resilience indicators for two life periods of each individual: natural logarithm-transformed variance (ln(variance)), skewness, and lag-one autocorrelation (autocorrelation) of deviations from 25 to 83 weeks of age and from 83 weeks of age to end of life. Then, we estimated their genetic correlations with EP traits and with two antibody traits.ResultsThe most promising resilience indicators were those based on 1-week-intervals, as they had the highest heritability estimates (0.02-0.12) and high genetic correlations (above 0.60) with the same resilience indicators based on longer intervals. The three types of resilience indicators differed genetically from each other, which indicates that they possibly capture different aspects of resilience. Genetic correlations of the resilience indicator traits based on 1-week-intervals with EP traits were favorable or zero, which means that trade-off effects were marginal. The resilience indicator traits based on 1-week-intervals also showed no genetic correlations with the antibody traits, which suggests that they are not informative for improved immunity or vice versa in the nucleus environment.ConclusionsThis paper gives direction towards the evaluation and implementation of resilience indicators, i.e. to further investigate resilience indicator traits based on 1-week-intervals, in breeding programs for selecting genetically more resilient layer chickens.

Dataset Information

Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods.

Publications

Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods.

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