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Selection of informative clusters from hierarchical cluster tree with gene classes.

ABSTRACT: BACKGROUND: A common clustering method in the analysis of gene expression data has been hierarchical clustering. Usually the analysis involves selection of clusters by cutting the tree at a suitable level and/or analysis of a sorted gene list that is obtained with the tree. Cutting of the hierarchical tree requires the selection of a suitable level and it results in the loss of information on the other level. Sorted gene lists depend on the sorting method of the joined clusters. Author proposes that the clusters should be selected using the gene classifications. RESULTS: This article presents a simple method for searching for clusters with the strongest enrichment of gene classes from a cluster tree. The clusters found are presented in the estimated order of importance. The method is demonstrated with a yeast gene expression data set and with two database classifications. The obtained clusters demonstrated a very strong enrichment of functional classes. The obtained clusters are also able to present similar gene groups to those that were observed from the data set in the original analysis and also many gene groups that were not reported in the original analysis. Visualization of the results on top of a cluster tree shows that the method finds informative clusters from several levels of the cluster tree and indicates that the clusters found could not have been obtained by simply cutting the cluster tree. Results were also used in the comparison of cluster trees from different clustering methods. CONCLUSION: The presented method should facilitate the exploratory analysis of big data sets when the associated categorical data is available.

SUBMITTER: Toronen P

PROVIDER: S-EPMC407846 | biostudies-other | 2004 Mar

REPOSITORIES: biostudies-other

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Selection of informative clusters from hierarchical cluster tree with gene classes.

Toronen Petri P

BMC bioinformatics 20040325

<h4>Background</h4>A common clustering method in the analysis of gene expression data has been hierarchical clustering. Usually the analysis involves selection of clusters by cutting the tree at a suitable level and/or analysis of a sorted gene list that is obtained with the tree. Cutting of the hierarchical tree requires the selection of a suitable level and it results in the loss of information on the other level. Sorted gene lists depend on the sorting method of the joined clusters. Author pr ...[more]

PMID: 15043761

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Project description:BackgroundIn the typical setting of gene-selection problems from high-dimensional data, e.g., gene expression data from microarray or next-generation sequencing-based technologies, an enormous volume of high-throughput data is generated, and there is often a need for a simple, computationally-inexpensive, non-parametric screening procedure than can quickly and accurately find a low-dimensional variable subset that preserves biological information from the original very high-dimensional data (dimension p > 40,000). This is in contrast to the very sophisticated variable selection methods that are computationally expensive, need pre-processing routines, and often require calibration of priors.ResultsWe present a tree-based sequential CART (S-CART) approach to variable selection in the binary classification setting and compare it against the more sophisticated procedures using simulated and real biological data. In simulated data, we analyze S-CART performance versus (i) a random forest (RF), (ii) a fully-parametric Bayesian stochastic search variable selection (SSVS), and (iii) the moderated t-test statistic from the LIMMA package in R. The simulation study is based on a hierarchical Bayesian model, where dataset dimensionality, percentage of significant variables, and substructure via dependency vary. Selection efficacy is measured through false-discovery and missed-discovery rates. In all scenarios, the S-CART method is seen to consistently outperform SSVS and RF in both speed and detection accuracy. We demonstrate the utility of the S-CART technique both on simulated data and in a control-treatment mouse study. We show that the network analysis based on the S-CART-selected gene subset in essence recapitulates the biological findings of the study using only a fraction of the original set of genes considered in the study's analysis.ConclusionsThe relatively simple-minded gene selection algorithms like S-CART may often in practical circumstances be preferred over much more sophisticated ones. The advantage of the "greedy" selection methods utilized by S-CART and the likes is that they scale well with the problem size and require virtually no tuning or training while remaining efficient in extracting the relevant information from microarray-like datasets containing large number of redundant or irrelevant variables.AvailabilityThe MATLAB 7.4b code for the S-CART implementation is available for download from https://neyman.mcg.edu/posts/scart.zip.

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Selection of informative clusters from hierarchical cluster tree with gene classes.

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Selection of informative clusters from hierarchical cluster tree with gene classes.

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