Multi-class cancer subtype classification based on gene expression signatures with reliability analysis

Differential diagnosis among a group of histologically similar cancers poses a challenging problem in clinical medicine. Constructing a classifier based on gene expression signatures comprising multiple discriminatory molecular markers derived from microarray data analysis is an emerging trend for cancer diagnosis. To identify the best genes for classification using a small number of samples relative to the genome size remains the bottleneck of this approach, despite its promise. We have devised a new method of gene selection with reliability analysis, and demonstrated that this method can identify a more compact set of genes than other methods for constructing a classifier with optimum predictive performance for both small round blue cell tumors and leukemia. High consensus between our result and the results produced by methods based on artificial neural networks and statistical techniques confers additional evidence of the validity of our method. This study suggests a way for implementing a reliable molecular cancer classifier based on gene expression signatures. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.