Tissue Classification with Gene Expression Profiles

A. Ben-Dor, L. Bruhn, N. Friedman, I. Nachman, M. Schummer, and Z. Yakhini

J. Computational Biology, 7: 559-584, 2000.



Constantly improving gene expression profiling technologies are expected to provide understanding and insight into cancer related cellular processes. Gene expression data is also expected to significantly aid in the development of efficient cancer diagnosis and classification platforms. In this work we examine three sets of gene expression data measured across sets of tumor(s) and normal clinical samples: The first set consists of 2,000 genes, measured in 62 epithelial colon samples [Alon et al. PNAS, 1999]. The second consists of ~100,000 clones, measured in 32 ovarian samples (unpublished extension of data set described in ; [Schummer et al, Gene, 1999]). The third set consists of ~7,100 genes, measured in 72 bone marrow and peripheral blood samples [Golub et al, Science, 1999].

We examine the use of scoring methods, measuring separation of tissue type (e.g., tumors from normals) using individual gene expression levels. These are then coupled with high dimensional classification methods to assess the classification power of complete expression profiles. We present results of performing leave-one-out cross validation (LOOCV) experiments on the three data sets, employingnearest neighbor classifier, SVM, AdaBoost and a novel clustering based classification technique. As tumor samples can differ from normal samples in their cell-type composition we also perform LOOCV experiments using appropriately modified sets of genes, attempting to eliminate the resulting bias.

We demonstrate success rate of at least 90 in tumor vs normal classification, using sets of selected genes, with as well as without cellular contamination related members. These results are insensitive to the exact selection mechanism, over a certain range.