Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

End stage renal disease (ESRD) is characterized by complex metabolic abnormalities, yet the clinical relevance of specific biomarkers remains unclear. The development of multiplex diagnostic platforms is creating opportunities to develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative multiplex proteomic platform which can measure >1300 proteins. In the present study, we performed SOMAscan analysis of plasma samples and validated the measurements by comparison with selected biomarkers. We compared concentrations of SOMAscan-measured prostate specific antigen (PSA) between males and females, and validated SOMAscan concentrations of fibroblast growth factor 23 (FGF23), FGF receptor 1 (FGFR1), and FGFR4 using Enzyme-Linked immunosorbent assay (ELISA). The median (25th and 75th percentile) SOMAscan PSA level in males and females was 4304.7 (1815.4 to 7259.5) and 547.8 (521.8 to 993.4) relative fluorescence units ( p = 0.002), respectively, suggesting biological plausibility. Pearson correlation between SOMAscan and ELISA was high for FGF23 ( R = 0.95, p < 0.001) and FGFR4 ( R = 0.69, p < 0.001), indicating significant positive correlation, while a weak correlation was found for FGFR1 ( R = 0.13, p = 0.16). In conclusion, there is a good to near-perfect correlation between SOMAscan and standard immunoassays for FGF23 and FGFR4, but not for FGFR1. This technology may be useful to simultaneously measure a large number of plasma proteins in ESRD, and identify clinically important prognostic markers to predict outcomes.

Related collections

Most cited references 28

Record: found
Abstract: found
Article: found

Is Open Access

Assessment of Variability in the SOMAscan Assay

Julián Candia, Foo Cheung, Yuri Kotliarov … (2017)

SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity and specificity. In this work, we present a comprehensive meta-analysis of performance based on multiple serum and plasma runs using the current 1.3 k assay, as well as the previous 1.1 k version. We discuss normalization procedures and examine different strategies to minimize intra- and interplate nuisance effects. We implement a meta-analysis based on calibrator samples to characterize the coefficient of variation and signal-over-background intensity of each protein analyte. By incorporating coefficient of variation estimates into a theoretical model of statistical variability, we also provide a framework to enable rigorous statistical tests of significance in intervention studies and clinical trials, as well as quality control within and across laboratories. Furthermore, we investigate the stability of healthy subject baselines and determine the set of analytes that exhibit biologically stable baselines after technical variability is factored in. This work is accompanied by an interactive web-based tool, an initiative with the potential to become the cornerstone of a regularly updated, high quality repository with data sharing, reproducibility, and reusability as ultimate goals.

0 comments Cited 144 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Obesity paradox in end-stage kidney disease patients.

Jongha Park, Seyed-Foad Ahmadi, Elani Streja … (2015)

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an "obesity paradox" or "reverse epidemiology" (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. © 2014.

0 comments Cited 100 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Advances in human proteomics at high scale with the SOMAscan proteomics platform.

Larry Gold, Jeffrey Walker, Sheri Wilcox … (2012)

In 1997, while still working at NeXstar Pharmaceuticals, several of us made a proteomic bet. We thought then, and continue to think, that proteomics offers a chance to identify disease-specific biomarkers and improve healthcare. However, interrogating proteins turned out to be a much harder problem than interrogating nucleic acids. Consequently, the 'omics' revolution has been fueled largely by genomics. High-scale proteomics promises to transform medicine with personalized diagnostics, prevention, and treatment. We have now reached into the human proteome to quantify more than 1000 proteins in any human matrix - serum, plasma, CSF, BAL, and also tissue extracts - with our new SOMAmer-based proteomics platform. The surprising and pleasant news is that we have made unbiased protein biomarker discovery a routine and fast exercise. The downstream implications of the platform are substantial.

0 comments Cited 95 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Diagnostics (Basel)

Journal ID (iso-abbrev): Diagnostics (Basel)

Journal ID (publisher-id): diagnostics

Title: Diagnostics

Publisher: MDPI

ISSN (Electronic): 2075-4418

Publication date (Electronic): 08 October 2018

Publication date Collection: December 2018

Volume: 8

Issue: 4

Electronic Location Identifier: 71

Affiliations

[1 ]Department of Medicine-Nephrology, University of Tennessee Health Science Center, Memphis, TN 38103, USA; zhan10@ 123456uthsc.edu (Z.H.); zxiao2@ 123456uthsc.edu (Z.X.); dquarles@ 123456uthsc.edu (L.D.Q.)

[2 ]Department of Medicine, University of California, Irvine, CA 92868, USA; kkz@ 123456uci.edu (K.K.-Z.); hmoradi@ 123456uci.edu (H.M.)

[3 ]Department of Epidemiology, Biostatistics and Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA; tshafi@ 123456jhmi.edu

[4 ]Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; swaikar@ 123456bwh.harvard.edu

[5 ]Johns Hopkins Bloomberg School of Public Health Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, MD 21205, USA; zyu33@ 123456jhmi.edu (Z.Y.); atin1@ 123456jhu.edu (A.T.); coresh@ 123456jhu.edu (J.C.)

[6 ]Nephrology Section, Memphis VA Medical Center, Memphis, TN 38104, USA

Author notes

[* ]Correspondence: ckovesdy@ 123456uthsc.edu ; Tel.: +1-901-448-2985

Author information

Zhousheng Xiao https://orcid.org/0000-0002-3363-5673

Csaba P. Kovesdy https://orcid.org/0000-0002-8204-911X

Article

Publisher ID: diagnostics-08-00071

DOI: 10.3390/diagnostics8040071

PMC ID: 6316431

PubMed ID: 30297602

SO-VID: c43f0194-1de8-44ae-94a0-c7a7b9821934

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease

Read this article at

Abstract

Related collections

Recursive Rule based Visual Categorization

Most cited references 28

Assessment of Variability in the SOMAscan Assay

Obesity paradox in end-stage kidney disease patients.

Advances in human proteomics at high scale with the SOMAscan proteomics platform.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 241

Cited by 6

Most referenced authors 981