Knowledge-Based Analysis of Microarray Gene Expression Data by Using Support Vector Machines

Michael P. S. Brown$^a$, William Noble Grundy$^c,*$, David Lin$^a$, Nello Cristianini$^d$, Charles Walsh Sugnet$^b$, Terrence S. Furey $^a$, Manuel Ares Jr.$^b$, and David Haussler $^a$

a. Department of Computer Science and
b. Center for Molecular Biology of RNA, Department of Biology, University of California, Santa Cruz, Santa Cruz, CA 95064
c. Department of Computer Science, Columbia University, New York, NY 10025
d. Department of Engineering Mathematics, University of Bristol, Bristol BS8 1TR, United Kingdom

*. To whom reprint requests should be addressed at: Department of Computer Science, Columbia University, 450 Computer Science Building, Mail Code 0401, 1214 Amsterdam Avenue, New York, NY 10027. E-mail: bgrundy@cs.columbia.edu.

Proceedings of the National Academy of Sciences, 97(1):262-267 (2000)


Abstract

We introduce a method of functionally classifying genes by using gene expression data from DNA microarray hybridization experiments. The method is based on the theory of support vector machines (SVMs). SVMs are considered a supervised computer learning method because they exploit prior knowledge of gene function to identify unknown genes of similar function from expression data. SVMs avoid several problems associated with unsupervised clustering methods, such as hierarchical clustering and self-organizing maps. SVMs have many mathematical features that make them attractive for gene expression analysis, including their flexibility in choosing a similarity function, sparseness of solution when dealing with large data sets, the ability to handle large feature spaces, and the ability to identify outliers. We test several SVMs that use different similarity metrics, as well as some other supervised learning methods, and find that the SVMs best identify sets of genes with a common function using expression data. Finally, we use SVMs to predict functional roles for uncharacterized yeast ORFs based on their expression data.

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