Identifying high-dimensional biomarkers for personalized medicine via variable importance ranking.

We apply robust classification algorithms to high-dimensional genomic data to find biomarkers, by analyzing variable importance, that enable a better diagnosis of disease, an earlier intervention, or a more effective assignment of therapies. The goal is to use variable importance ranking to isolate a set of important genes that can be used to classify life-threatening diseases with respect to prognosis or type to maximize efficacy or minimize toxicity in personalized treatment of such diseases. A ranking method and present several other methods to select a set of important genes to use as genomic biomarkers is proposed, and the performance of the selection procedures in patient classification by cross-validation is evaluated. The various selection algorithms are applied to published high-dimensional genomic data sets using several well-known classification methods. For each data set, a set of genes selected on the basis of variable importance that performed the best in classification is reported. That classification algorithm with the proposed ranking method is shown to be competitive with other selection methods for discovering genomic biomarkers underlying both adverse and efficacious outcomes for improving individualized treatment of patients for life-threatening diseases.