title: Microarray based diagnosis profits from better documentation of gene expression signatures.
abstract: Microarray gene expression signatures hold great promise to improve diagnosis and prognosis of disease. However, current documentation standards of such signatures do not allow for an unambiguous application to study-external patients. This hinders independent evaluation, effectively delaying the use of signatures in clinical practice. Data from eight publicly available clinical microarray studies were analyzed and the consistency of study-internal with study-external diagnoses was evaluated. Study-external classifications were based on documented information only. Documenting a signature is conceptually different from reporting a list of genes. We show that even the exact quantitative specification of a classification rule alone does not define a signature unambiguously. We found that discrepancy between study-internal and study-external diagnoses can be as frequent as 30% (worst case) and 18% (median). By using the proposed documentation by value strategy, which documents quantitative preprocessing information, the median discrepancy was reduced to 1%. The process of evaluating microarray gene expression diagnostic signatures and bringing them to clinical practice can be substantially improved and made more reliable by better documentation of the signatures.
authors.affiliation: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. dkostka@ucdavis.edu
authors.forename: Dennis
authors.initials: D
authors.lastname: Kostka
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004282:Documentation / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins