Title: A stability-based algorithm to validate hierarchical clusters of genes

Authors: Roberto Avogadri, Matteo Brioschi, Fulvia Ferrazzi, Matteo Re, Alessandro Beghini, Giorgio Valentini

Addresses: DSI – Dip. Scienze dell' Informazione, Universita degli Studi di Milano, via Comelico 39/41, 20135 Milano MI, Italy. ' DBioGen – Dip. Biologia e Genetica per le Scienze Mediche, Universita degli Studi di Milano, via G. B. Viotti 3/5, 20133 Milano MI, Italy. ' Dip. Informatica e Sistemistica, Universita degli Studi di Pavia, via Ferrata 1, 27100 Pavia PV, Italy. ' DSI – Dip. Scienze dell' Informazione, Universita degli Studi di Milano, via Comelico 39/41, 20135 Milano MI, Italy. ' DBioGen – Dip. Biologia e Genetica per le Scienze Mediche, Universita degli Studi di Milano, via G. B. Viotti 3/5, 20133 Milano MI, Italy.' DSI – Dip. Scienze dell' Informazione, Universita degli Studi di Milano, via Comelico 39/41, 20135 Milano MI, Italy

Abstract: Stability-based methods have been successfully applied in functional genomics to the analysis of the reliability of clusterings characterised by a relatively low number of examples and clusters. The application of these methods to the validation of gene clusters discovered in biomolecular data may lead to computational problems due to the large amount of possible clusters involved. To address this problem, we present a stability-based algorithm to discover significant clusters in hierarchical clusterings with a large number of examples and clusters. The reliability of clusters of genes discovered in gene expression data of patients affected by human myeloid leukaemia is analysed through the proposed algorithm, and their relationships with specific biological processes are tested by means of Gene Ontology-based functional enrichment methods.

Keywords: hierarchical clustering; stability based methods; cluster validation; DNA microarray; gene clusters; functional genomics; ontology; gene expression data; human myeloid leukaemia; bioinformatics.

DOI: 10.1504/IJKESDP.2009.028985

International Journal of Knowledge Engineering and Soft Data Paradigms, 2009 Vol.1 No.4, pp.318 - 330

Published online: 19 Oct 2009 *

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