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This article is part of the supplement: IEEE 7th International Conference on Bioinformatics and Bioengineering at Harvard Medical School

Open Access Research

Extending bicluster analysis to annotate unclassified ORFs and predict novel functional modules using expression data

Kenneth Bryan* and Pádraig Cunningham

Author Affiliations

Complex and Adaptive Systems Laboratory (CASL), University College Dublin, Belfield, Dublin 4, Ireland

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BMC Genomics 2008, 9(Suppl 2):S20  doi:10.1186/1471-2164-9-S2-S20

Published: 16 September 2008



Microarrays have the capacity to measure the expressions of thousands of genes in parallel over many experimental samples. The unsupervised classification technique of bicluster analysis has been employed previously to uncover gene expression correlations over subsets of samples with the aim of providing a more accurate model of the natural gene functional classes. This approach also has the potential to aid functional annotation of unclassified open reading frames (ORFs). Until now this aspect of biclustering has been under-explored. In this work we illustrate how bicluster analysis may be extended into a 'semi-supervised' ORF annotation approach referred to as BALBOA.


The efficacy of the BALBOA ORF classification technique is first assessed via cross validation and compared to a multi-class k-Nearest Neighbour (kNN) benchmark across three independent gene expression datasets. BALBOA is then used to assign putative functional annotations to unclassified yeast ORFs. These predictions are evaluated using existing experimental and protein sequence information. Lastly, we employ a related semi-supervised method to predict the presence of novel functional modules within yeast.


In this paper we demonstrate how unsupervised classification methods, such as bicluster analysis, may be extended using of available annotations to form semi-supervised approaches within the gene expression analysis domain. We show that such methods have the potential to improve upon supervised approaches and shed new light on the functions of unclassified ORFs and their co-regulation.