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Jackson D, Herath A, Swinton J, et al. Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome. Proteomics Clin Appl. 2009;3(3):394-407doi: 10.1002/prca.200800066.
Jackson, D., Herath, A., Swinton, J., Bramwell, D., Chopra, R., Hughes, A., Cheeseman, K., & Tonge, R. (2009). Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome. Proteomics. Clinical applications, 3(3), 394-407. https://doi.org/10.1002/prca.200800066
Jackson, David, et al. "Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome." Proteomics. Clinical applications vol. 3,3 (2009): 394-407. doi: https://doi.org/10.1002/prca.200800066
Jackson D, Herath A, Swinton J, Bramwell D, Chopra R, Hughes A, Cheeseman K, Tonge R. Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome. Proteomics Clin Appl. 2009 Mar;3(3):394-407. doi: 10.1002/prca.200800066. Epub 2009 Feb 13. PMID: 26238755.
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Proteomics Clin Appl. 2009 Mar;3(3):394-407. doi: 10.1002/prca.200800066. Epub 2009 Feb 13.

Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome.

Proteomics. Clinical applications

David Jackson, Athula Herath, Jonathan Swinton, David Bramwell, Rajesh Chopra, Andrew Hughes, Kevin Cheeseman, Robert Tonge

Affiliations

  1. AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, UK. [email protected].
  2. AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, UK.
  3. Nonlinear Dynamics, Newcastle, UK.
  4. Current address: Clinical and Biomedical Proteomics Group, Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds,UK.

PMID: 26238755 DOI: 10.1002/prca.200800066

Abstract

Proteomics is increasingly being applied to the human plasma proteome to identify biomarkers of disease for use in non-invasive assays. 2-D DIGE, simultaneously analysing thousands of protein spots quantitatively and maintaining protein isoform information, is one technique adopted. Sufficient numbers of samples must be analysed to achieve statistical power; however, few reported studies have analysed inherent variability in the plasma proteome by 2-D DIGE to allow power calculations. This study analysed plasma from 60 healthy volunteers by 2-D DIGE. Two samples were taken, 7 days apart, allowing estimation of sensitivity of detection of differences in spot intensity between two groups using either a longitudinal (paired) or non-paired design. Parameters for differences were: two-fold normalised volume change, α of 0.05 and power of 0.8. Using groups of 20 samples, alterations in 1742 spots could be detected with longitudinal sampling, and in 1206 between non-paired groups. Interbatch gel variability was small relative to the detection parameters, indicating robustness and reproducibility of 2-D DIGE for analysing large sample sets. In summary, 20 samples can allow detection of a large number of proteomic alterations by 2-D DIGE in human plasma, the sensitivity of detecting differences was greatly improved by longitudinal sampling and the technology was robust across batches.

Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords: 2‐D DIGE; Image analysis; Plasma; Statistical power; Variability

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