Evaluation of methods for gene selection in melanoma cell lines

Abstract

A major objective in microarray experiments is to identify a panel of genes that are associated with a disease outcome or trait. Many statistical methods have been proposed for gene selection within the last fifteen years. While the comparison of some of these methods has been done, most of them concentrated on finding gene signatures based on two groups. This study evaluates four gene selection methods when the outcome of interested is continuous in nature. We provide a comparative review of four methods: the Statistical Analysis of Microarrays (SAM), the Linear Models for Microarray Analysis (LIMMA), the Lassoed Principal Components (LPC), and the Quantitative Trait Analysis (QTA). Comparison is based on the power to identify differentially expressed genes, the predictive ability of the genelists for a continuous outcome (G2 checkpoint function), and the prognostic properties of the genelists for distant metastasis-free survival. A simulated dataset and a publicly available melanoma cell lines dataset are used for simulations and validation, respectively. A primary melanoma dataset is used for assessment of prognosis. No common genes were found among the genelists from the four methods. While the SAM was generally the best in terms of power, the QTA genelist performed the best in the prediction of the G2 checkpoint function. Identification of genelists depends on the choice of the gene selection method. The QTA method would be preferred over the other approaches in predicting a quantitative outcome in melanoma research. We recommend the development of more robust statistical methods for differential gene expression analysis.