Biology Reference
In-Depth Information
Chapter 14
Study Design in DIGE-Based Biomarker Discovery
Alexandra Graf and Rudolf Oehler
Abstract
The DIGE technology allows the detection of small differences in the expression level of abundant proteins.
Many diseases are associated with quantitative deviations of proteins which might represent useful
biomarkers for diagnosis or prognosis. DIGE is therefore a highly convenient method for the character-
ization of disease-related expression changes. This chapter focuses on the study design in DIGE-based
biomarker discovery. It introduces the statistical implications of testing thousands of proteins in parallel
and discusses the solutions proposed by the literature. The outline provided in the method section tries to
guide the researcher through the different statistical considerations, which have to be taken into account
in biomarker detection. Special emphasis is given to the use of sample sizes of suffi cient statistical power
and to the statistical evaluation of the results.
Key words:
Sample size calculation, Power calculation, Clinical proteomics, Biomarker research,
Study design, DIGE
1. Introduction
Clinical proteomics tries to get a “holistic” view on the pathobiochemistry
of a disease. The hope is that this approach increases the probability
to fi nd those proteins which are indicative for the pathogenic process
and can be used as biomarkers. Biomarkers are classifi ed as antecedent
biomarkers (identifying the risk of developing an illness), screening
biomarkers (screening for subclinical disease), diagnostic biomarkers
(recognizing overt disease), staging biomarkers (categorizing disease
severity), or prognostic biomarkers (predicting future disease course,
including recurrence and response to therapy, and monitoring effi -
cacy of therapy). Biomarkers may also serve as surrogate end points.
Although there is limited consensus on this issue, a surrogate end
point is one that can be used as an outcome in clinical trials to
evaluate safety and effectiveness of therapies in lieu of measurement
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