Trustworthiness and metrics in visualizing similarity of gene expression

BACKGROUND: Conventionally, the first step in analyzing the large and high-dimensional data sets measured by microarrays is visual exploration. Dendrograms of hierarchical clustering, self-organizing maps (SOMs), and multidimensional scaling have been used to visualize similarity relationships of data samples. We address two central properties of the methods: (i) Are the visualizations trustworthy, i.e., if two samples are visualized to be similar, are they really similar? (ii) The metric. The measure of similarity determines the result; we propose using a new learning metrics principle to derive a metric from interrelationships among data sets. RESULTS: The trustworthiness of hierarchical clustering, multidimensional scaling, and the self-organizing map were compared in visualizing similarity relationships among gene expression profiles. The self-organizing map was the best except that hierarchical clustering was the most trustworthy for the most similar profiles. Trustworthiness can be further increased by treating separately those genes for which the visualization is least trustworthy. We then proceed to improve the metric. The distance measure between the expression profiles is adjusted to measure differences relevant to functional classes of the genes. The genes for which the new metric is the most different from the usual correlation metric are listed and visualized with one of the visualization methods, the self-organizing map, computed in the new metric. CONCLUSIONS: The conjecture from the methodological results is that the self-organizing map can be recommended to complement the usual hierarchical clustering for visualizing and exploring gene expression data. Discarding the least trustworthy samples and improving the metric still improves it

Learning metrics and discriminative clustering

In this work methods have been developed to extract relevant information from large, multivariate data sets in a flexible, nonlinear way. The techniques are applicable especially at the initial, explorative phase of data analysis, in cases where an explicit indicator of relevance is available as part of the data set. The unsupervised learning methods, popular in data exploration, often rely on a distance measure defined for data items. Selection of the distance measure, part of which is feature selection, is therefore fundamentally important. The learning metrics principle is introduced to complement manual feature selection by enabling automatic modification of a distance measure on the basis of available relevance information. Two applications of the principle are developed. The first emphasizes relevant aspects of the data by directly modifying distances between data items, and is usable, for example, in information visualization with the self-organizing maps. The other method, discriminative clustering, finds clusters that are internally homogeneous with respect to the interesting variation of the data. The techniques have been applied to text document analysis, gene expression clustering, and charting the bankruptcy sensitivity of companies. In the first, more straightforward approach, a new local metric of the data space measures changes in the conditional distribution of the relevance-indicating data by the Fisher information matrix, a local approximation of the Kullback-Leibler distance. Discriminative clustering, on the other hand, directly minimizes a Kullback-Leibler based distortion measure within the clusters, or equivalently maximizes the mutual information between the clusters and the relevance indicator. A finite-data algorithm for discriminative clustering is also presented. It maximizes a partially marginalized posterior probability of the model and is asymptotically equivalent to maximizing mutual information.reviewe

Learning More Accurate Metrics for Self-Organizing Maps

Improved methods are presented for learning metrics that measure only important distances. It is assumed that changes in primary data are relevant only to the extent that they cause changes in auxiliary data, available paired with the primary data. The metrics are here derived from estimators of the conditional density of the auxiliary data. More accurate estimators are compared, and a more accurate approximation to the distances is introduced. The new methods improved the quality of Self-Organizing Maps (SOMs) significantly for four of the five studied data sets