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Article type: Research Article
Authors: Clare, Amanda | King, Ross D.
Affiliations: Department of Computer Science, University of Wales Aberystwyth, Penglais, Aberystwyth SY23 3DB, UK
Note: [] Corresponding author: Amanda Clare, Department of Computer Science, University of Wales Aberystwyth, Penglais, Aber-ystwyth SY23 3DB, UK. Fax: +44 1970 622455; E-mail: [email protected].
Abstract: We wished to quantify the state-of-the-art of our understanding of clusters in microarray data. To do this we systematically compared the clusters produced on sets of microarray data using a representative set of clustering algorithms (hierarchical, k-means, and a modified version of QT_CLUST) with the annotation schemes MIPS, GeneOntology and GenProtEC. We assumed that if a cluster reflected known biology its members would share related ontological annotations. This assumption is the basis of guilt-by-association and is commonly used to assign the putative function of proteins. To statistically measure the relationship between cluster and annotation we developed a new predictive discriminatory measure. We found that the clusters found in microarray data do not in general agree with functional annotation classes. Although many statistically significant relationships can be found, the majority of clusters are not related to known biology (as described in annotation ontologies). This implies that use of guilt-by-association is not supported by annotation ontologies. Depending on the estimate of the amount of noise in the data, our results suggest that bioinformatics has only codified a small proportion of the biological knowledge required to understand microarray data. The annotated clusters can be found at http://www.aber.ac.uk/compsci/Research/bio/dss/gba/.
Keywords: ontology, machine-learning, transcriptome, microarray data, statistics
Journal: In Silico Biology, vol. 2, no. 4, pp. 511-522, 2002
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