Documentation of Diagnostic Signatures
Background: It has been shown that microarray based gene expression signatures are a powerful tool for patient stratification, diagnosis of disease, prognosis of survival, assessment of risk group and selection of treatment. However, documentation standards in current publications do not allow for a signatures unambiguous application to study-external patients. This hinders independent evaluation, effectively delaying the use of signatures in clinical practice. Documenting a signature is conceptually different from reporting a list of genes, since the latter does not determine how a study-external patient should be diagnosed.
Our approach: One prominent reason for ambiguity in gene expression
signatures lies in the data preprocessing common to microarray studies: Estimates of expression values for a fixed
microarray change when additional arrays are added to the study and preprocessing is
repeated. This is a severe problem for applying a signature to study-external data:
The original data needs to be included in the normalization of external arrays. The re-normalization
of the complete data set changes the original expression values, affecting
the signature and the molecular diagnosis of patients in the original study.
Software will be made available in form of an R package upon publication