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Rule-based Clustering for Gene Promoter Structure Discovery

Journal:Methods of Information in Medicine
Subtitle:A journal stressing, for more than 50 years, the methodology and scientific fundamentals of organizing, representing and analyzing data, information and knowledge in biomedicine and health care
ISSN:0026-1270
Topic:

Special Topic: Biomedical Data Mining
Guest Editors: N. Peek, C. Combi, A. Tucker

DOI:http://dx.doi.org/10.3414/ME9225
Issue:2009 (Vol. 48): Issue 3 2009
Pages:229-235

Rule-based Clustering for Gene Promoter Structure Discovery

T. Curk (1), U. Petrovic (2), G. Shaulsky (3), B. Zupan (3, 1)

(1) University of Ljubljana, Faculty of Computer and Information Science, Ljubljana, Slovenia; (2) J. Stefan Institute, Department of Molecular and Biomedical Sciences, Ljubljana, Slovenia; (3) Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, Texas, USA

Summary

Background: The genetic cellular response to internal and external changes is determined by the sequence and structure of gene-regulatory promoter regions. Objectives: Using data on gene-regulatory elements (i.e., either putative or known transcription factor binding sites) and data on gene expression profiles we can discover structural elements in promoter regions and infer the underlying programs of gene regulation. Such hypotheses obtained in silico can greatly assist us in experiment planning. The principal obstacle for such approaches is the combinatorial explosion in different combinations of promoter elements to be examined. Methods: Stemming from several state-of-the-art machine learning approaches we here propose a heuristic, rule-based clustering method that uses gene expression similarity to guide the search for informative structures in promoters, thus exploring only the most promising parts of the vast and expressively rich rule-space. Results: We present the utility of the method in the analysis of gene expression data on budding yeast S. cerevisiae where cells were induced to proliferate peroxisomes. Conclusions: We demonstrate that the proposed approach is able to infer informative relations uncovering relatively complex structures in gene promoter regions that regulate gene expression.

Keywords

Machine Learning, Promoter analysis, gene expression analysis, rule-based clustering

DOI

http://dx.doi.org/10.3414/ME9225

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