Inference from clustering with application to gene-expression microarrays

Edward R. Dougherty, Junior Barrera, Marcel Brun, Seungchan Kim, Roberto M. Cesar, Yidong Chen, Michael Bittner, Jeffrey M. Trent

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

There are many algorithms to cluster sample data points based on nearness or a similarity measure. Often the implication is that points in different clusters come from different underlying classes, whereas those in the same cluster come from the same class. Stochastically, the underlying classes represent different random processes. The inference is that clusters represent a partition of the sample points according to which process they belong. This paper discusses a model-based clustering toolbox that evaluates cluster accuracy. Each random process is modeled as its mean plus independent noise, sample points are generated, the points are clustered, and the clustering error is the number of points clustered incorrectly according to the generating random processes. Various clustering algorithms are evaluated based on process variance and the key issue of the rate at which algorithmic performance improves with increasing numbers of experimental replications. The model means can be selected by hand to test the separability of expected types of biological expression patterns. Alternatively, the model can be seeded by real data to test the expected precision of that output or the extent of improvement in precision that replication could provide. In the latter case, a clustering algorithm is used to form clusters, and the model is seeded with the means and variances of these clusters. Other algorithms are then tested relative to the seeding algorithm. Results are averaged over various seeds. Output includes error tables and graphs, confusion matrices, principal-component plots, and validation measures. Five algorithms are studied in detail: K-means, fuzzy C-means, self-organizing maps, hierarchical Euclidean-distance-based and correlation-based clustering. The toolbox is applied to gene-expression clustering based on cDNA microarrays using real data. Expression profile graphics are generated and error analysis is displayed within the context of these profile graphics. A large amount of generated output is available over the web.

Original languageEnglish (US)
Pages (from-to)105-126
Number of pages22
JournalJournal of Computational Biology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Keywords

  • Clustering
  • Gene expression
  • Microarray

ASJC Scopus subject areas

  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Computational Mathematics
  • Computational Theory and Mathematics

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  • Cite this

    Dougherty, E. R., Barrera, J., Brun, M., Kim, S., Cesar, R. M., Chen, Y., Bittner, M., & Trent, J. M. (2002). Inference from clustering with application to gene-expression microarrays. Journal of Computational Biology, 9(1), 105-126. https://doi.org/10.1089/10665270252833217