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Statistical Issues in the Design and Planning of Proteomic Profiling Experiments

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Clinical Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1243))

Abstract

The statistical design of a clinical proteomics experiment is a critical part of well-undertaken investigation. Standard concepts from experimental design such as randomization, replication and blocking should be applied in all experiments, and this is possible when the experimental conditions are well understood by the investigator. The large number of proteins simultaneously considered in proteomic discovery experiments means that determining the number of required replicates to perform a powerful experiment is more complicated than in simple experiments. However, by using information about the nature of an experiment and making simple assumptions this is achievable for a variety of experiments useful for biomarker discovery and initial validation.

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References

  1. Hanash SM, Pitteri SJ, Faca VM (2008) Mining the plasma proteome for cancer biomarkers. Nature 452:571–579

    Article  CAS  PubMed  Google Scholar 

  2. Poste G (2011) Bring on the biomarkers. Nature 469:156–157

    Article  CAS  PubMed  Google Scholar 

  3. Fisher RA (1938) Presidential Address by Professor R. A. Fisher, Sc.D., F.R.S. Sankhyā Indian J Stat 4:14–17

    Google Scholar 

  4. Hu J, Coombes KR, Morris JS et al (2005) The importance of experimental design in proteomic mass spectrometry experiments: some cautionary tales. Brief Funct Genomic Proteomic 3:322–331

    Article  CAS  PubMed  Google Scholar 

  5. Petricoin EF, Ardekani AM, Hitt BA et al (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359:572–577

    Article  CAS  PubMed  Google Scholar 

  6. Baggerly KA, Coombes KR, Morris JS (2005) Bias, randomization, and ovarian proteomic data: a reply to “producers and consumers”. Cancer Inform 1:9–14

    PubMed Central  PubMed  Google Scholar 

  7. Liotta LA, Lowenthal M, Mehta A et al (2005) Importance of communication between producers and consumers of publicly available experimental data. J Natl Cancer Inst 97:310–314

    Article  PubMed  Google Scholar 

  8. Baggerly KA, Morris JS, Coombes KR (2004) Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments. Bioinformatics 20:777–785

    Article  CAS  PubMed  Google Scholar 

  9. Atkinson AJ, Colburn WA, DeGruttola VG et al (2001) Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  10. Cho D, McDermott D, Atkins M (2006) Designing clinical trials for kidney cancer based on newly developed prognostic and predictive tools. Curr Urol Rep 7:8–15

    Article  PubMed  Google Scholar 

  11. Jain RK, Duda DG, Willett CG et al (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6:327–338

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Mandrekar SJ, Sargent DJ (2009) Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges. J Clin Oncol 27:4027–4034

    Article  PubMed Central  PubMed  Google Scholar 

  13. Oberg A, Vitek O (2009) Statistical design of quantitative mass spectrometry-based proteomic profiling experiments. J Proteome Res 8:2144–2156

    Article  CAS  PubMed  Google Scholar 

  14. Fisher RA (1937) The design of experiments, 2nd edn. Oliver & Boyd, Edinburgh

    Google Scholar 

  15. Karp NA, Spencer M, Lindsay H et al (2005) Impact of replicate types on proteomic expression analysis. J Proteome Res 4:1867–1871

    Article  CAS  PubMed  Google Scholar 

  16. Eckel-Passow JE, Hoering A, Therneau TM et al (2005) Experimental design and analysis of antibody microarrays: applying methods from cDNA arrays. Cancer Res 65:2985–2989

    CAS  PubMed  Google Scholar 

  17. Song X, Bandow J, Sherman J et al (2008) iTRAQ experimental design for plasma biomarker discovery. J Proteome Res 7:2952–2958

    Article  CAS  PubMed  Google Scholar 

  18. Yang YH, Speed T (2002) Design issues for cDNA microarray experiments. Nat Rev Genet 3:579–588

    CAS  PubMed  Google Scholar 

  19. Chow S-C, Shao J, Wang H (2008) Sample size calculations in clinical research. Chapman & Hall/CRC biostatistics series, vol 20, 2nd edn. Chapman & Hall/CRC, Boca Raton, FL

    Google Scholar 

  20. Obuchowski NA, Lieber ML, Wians FH Jr (2004) ROC curves in clinical chemistry: uses, misuses, and possible solutions. Clin Chem 50:1118–1125

    Article  CAS  PubMed  Google Scholar 

  21. Schoenfeld DA (1983) Sample-size formula for the proportional-hazards regression-model. Biometrics 39:499–503

    Article  CAS  PubMed  Google Scholar 

  22. Hsieh FY, Lavori PW (2000) Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates. Control Clin Trials 21:552–560

    Article  CAS  PubMed  Google Scholar 

  23. Bartlett JMS, Brookes CL, Robson T et al (2011) Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol 29:1531–1538

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B Met 57:289–300

    Google Scholar 

  25. Dobbin K, Simon R (2005) Sample size determination in microarray experiments for class comparison and prognostic classification. Biostatistics 6:27–38

    Article  PubMed  Google Scholar 

  26. Eckel-Passow JE, Oberg AL, Therneau TM et al (2009) An insight into high-resolution mass-spectrometry data. Biostatistics 10:481–500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Skates SJ, Gillette MA, Labaer J et al (2013) Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies. J Proteome Res 12:5383–5394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Cairns DA, Barrett JH, Billingham LJ et al (2009) Sample size determination in clinical proteomic profiling experiments using mass spectrometry for class comparison. Proteomics 9:74–86

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by a Career Development Award from the UK Medical Research Council [G0802416].

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Correspondence to David A. Cairns .

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Cairns, D.A. (2015). Statistical Issues in the Design and Planning of Proteomic Profiling Experiments. In: Vlahou, A., Makridakis, M. (eds) Clinical Proteomics. Methods in Molecular Biology, vol 1243. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1872-0_13

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  • DOI: https://doi.org/10.1007/978-1-4939-1872-0_13

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1871-3

  • Online ISBN: 978-1-4939-1872-0

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