Kernel-based data fusion and its application to protein function prediction in yeast.

Kernel methods provide a principled framework in which to represent many types of data, including vectors, strings, trees and graphs. As such, these methods are useful for drawing inferences about biological phenomena. We describe a method for combining multiple kernel representations in an optimal fashion, by formulating the problem as a convex optimization problem that can be solved using semidefinite programming techniques. The method is applied to the problem of predicting yeast protein functional classifications using a support vector machine (SVM) trained on five types of data. For this problem, the new method performs better than a previously-described Markov random field method, and better than the SVM trained on any single type of data.

Support vector machine classification and validation of cancer tissue samples using microarray expression data.

MOTIVATION: DNA microarray experiments generating thousands of gene expression measurements, are being used to gather information from tissue and cell samples regarding gene expression differences that will be useful in diagnosing disease. We have developed a new method to analyse this kind of data using support vector machines (SVMs). This analysis consists of both classification of the tissue samples, and an exploration of the data for mis-labeled or questionable tissue results. RESULTS: We demonstrate the method in detail on samples consisting of ovarian cancer tissues, normal ovarian tissues, and other normal tissues. The dataset consists of expression experiment results for 97,802 cDNAs for each tissue. As a result of computational analysis, a tissue sample is discovered and confirmed to be wrongly labeled. Upon correction of this mistake and the removal of an outlier, perfect classification of tissues is achieved, but not with high confidence. We identify and analyse a subset of genes from the ovarian dataset whose expression is highly differentiated between the types of tissues. To show robustness of the SVM method, two previously published datasets from other types of tissues or cells are analysed. The results are comparable to those previously obtained. We show that other machine learning methods also perform comparably to the SVM on many of those datasets. AVAILABILITY: The SVM software is available at http://www.cs. columbia.edu/ approximately bgrundy/svm.

Knowledge-based analysis of microarray gene expression data by using support vector machines.

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.