Dataset Information

Merged consensus clustering to assess and improve class discovery with microarray data.

ABSTRACT: One of the most commonly performed tasks when analysing high throughput gene expression data is to use clustering methods to classify the data into groups. There are a large number of methods available to perform clustering, but it is often unclear which method is best suited to the data and how to quantify the quality of the classifications produced.Here we describe an R package containing methods to analyse the consistency of clustering results from any number of different clustering methods using resampling statistics. These methods allow the identification of the the best supported clusters and additionally rank cluster members by their fidelity within the cluster. These metrics allow us to compare the performance of different clustering algorithms under different experimental conditions and to select those that produce the most reliable clustering structures. We show the application of this method to simulated data, canonical gene expression experiments and our own novel analysis of genes involved in the specification of the peripheral nervous system in the fruitfly, Drosophila melanogaster.Our package enables users to apply the merged consensus clustering methodology conveniently within the R programming environment, providing both analysis and graphical display functions for exploring clustering approaches. It extends the basic principle of consensus clustering by allowing the merging of results between different methods to provide an averaged clustering robustness. We show that this extension is useful in correcting for the tendency of clustering algorithms to treat outliers differently within datasets. The R package, clusterCons, is freely available at CRAN and sourceforge under the GNU public licence.

SUBMITTER: Simpson TI

PROVIDER: S-EPMC3002369 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Merged consensus clustering to assess and improve class discovery with microarray data.

Simpson T Ian TI Armstrong J Douglas JD Jarman Andrew P AP

BMC bioinformatics 20101203

<h4>Background</h4>One of the most commonly performed tasks when analysing high throughput gene expression data is to use clustering methods to classify the data into groups. There are a large number of methods available to perform clustering, but it is often unclear which method is best suited to the data and how to quantify the quality of the classifications produced.<h4>Results</h4>Here we describe an R package containing methods to analyse the consistency of clustering results from any numbe ...[more]

PMID: 21129181

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Project description:BACKGROUND:Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. RESULT:We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered), missing value imputation (2), standardization of data (2), gene selection (19) or clustering method (11). The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that background correction is preferable, in particular if the gene selection is successful. However, this is an area that needs to be studied further in order to draw any general conclusions. CONCLUSIONS:The choice of cluster analysis, and in particular gene selection, has a large impact on the ability to cluster individuals correctly based on expression profiles. Normalization has a positive effect, but the relative performance of different normalizations is an area that needs more research. In summary, although clustering, gene selection and normalization are considered standard methods in bioinformatics, our comprehensive analysis shows that selecting the right methods, and the right combinations of methods, is far from trivial and that much is still unexplored in what is considered to be the most basic analysis of genomic data.

Project description:BACKGROUND: Clustering is a popular data exploration technique widely used in microarray data analysis. Most conventional clustering algorithms, however, generate only one set of clusters independent of the biological context of the analysis. This is often inadequate to explore data from different biological perspectives and gain new insights. We propose a new clustering model that can generate multiple versions of different clusters from a single dataset, each of which highlights a different aspect of the given dataset. RESULTS: By applying our SigCalc algorithm to three yeast Saccharomyces cerevisiae datasets we show two results. First, we show that different sets of clusters can be generated from the same dataset using different sets of landmark genes. Each set of clusters groups genes differently and reveals new biological associations between genes that were not apparent from clustering the original microarray expression data. Second, we show that many of these new found biological associations are common across datasets. These results also provide strong evidence of a link between the choice of landmark genes and the new biological associations found in gene clusters. CONCLUSION: We have used the SigCalc algorithm to project the microarray data onto a completely new subspace whose co-ordinates are genes (called landmark genes), known to belong to a Biological Process. The projected space is not a true vector space in mathematical terms. However, we use the term subspace to refer to one of virtually infinite numbers of projected spaces that our proposed method can produce. By changing the biological process and thus the landmark genes, we can change this subspace. We have shown how clustering on this subspace reveals new, biologically meaningful clusters which were not evident in the clusters generated by conventional methods. The R scripts (source code) are freely available under the GPL license. The source code is available [see Additional File 1] as additional material, and the latest version can be obtained at http://www4.ncsu.edu/~pchopra/landmarks.html. The code is under active development to incorporate new clustering methods and analysis.

Dataset Information

Merged consensus clustering to assess and improve class discovery with microarray data.

Publications

Merged consensus clustering to assess and improve class discovery with microarray data.

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