'Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns

We illustrate the use of the gene shaving method to analyze gene expression measurements made on samples from patients with diffuse large B-cell lymphoma. The method identifies a small cluster of genes whose expression is highly predictive of survival.The gene shaving method is a potentially useful tool for exploration of gene expression data and identification of interesting clusters of genes worth further investigation.Through the use of recently developed DNA arrays, it is now possible to obtain accurate, quantitative (relative) measurements of a large proportion of the mRNA species present in a biological sample. DNA arrays have been used to monitor changes in gene expression during important biological processes (for example, cellular replication and the response to changes in the environment), and to study variation in gene expression across collections of related samples (such as tumor samples from patients with cancer). A major challenge in interpreting these results is to understand the structure of the data produced by such studies, which often consist of millions of measurements. A variety of clustering techniques have been applied to such data, and have proved useful for identifying biologically relevant groupings of genes and samples [1,2,3,4,5,6,7,8,9,10,11,12,13]. Although the underlying principles and computational details of these methods differ, they share the goal of organizing the elements under consideration (such as genes) into groups (clusters) with coherent behavior across relevant measurements (such as samples). Generally absent is any consideration of the nature of the coherent variation. For example, one might want to identify groups of genes that have coherent patterns of expression with large variance across samples, or groups of genes that optimally separate samples into predefined classes (such as different clinical response groups in tumor samples). Here, we introduce a new statistical method, which we call gene shaving, that attempts