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Early diagnostic marker panel determination for microarray based clinical studies


Jaeger,  Jochen
Max Planck Society;

Spang,  Rainer
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Jaeger, J., Weichenhan, D., Ivandic, B., & Spang, R. (2005). Early diagnostic marker panel determination for microarray based clinical studies. Statistical Applications in Genetics and Molecular Biology, 4(1), Article 9-Article 9.

We present a novel, cost efficient two-phase design for predictive clinical gene expression studies: early marker panel determination (EMPD). In Phase-1, genome-wide microarrays are used only for a small number of individual patient samples. From this Phase-1 data a panel of marker genes is derived. In Phase-2, the expression values of these marker panel genes are measured for a large group of patients and a predictive classification model is learned from this data. Phase-2 does not require the use of expensive whole genome microarrays, thus making EMPD a cost efficient alternative for current trials. The expected performance loss of EMPD is compared to designs which use genome-wide microarrays for all patients. We also examine the trade-off between the number of patients included in Phase-1 and the number of marker genes required in Phase-2. By analysis of five published datasets we find that in Phase-1 already 16 patients per group are sufficient to determine a suitable marker panel of 10 genes, and that this early decision compromises the final performance only marginally.