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Nucleic Acids Research, 2002, Vol. 30, No. 11 2599-2607
© 2002 Oxford University Press

Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics

Kui Lin, Yuyu Kuang, Jeremiah S. Joseph and Prasanna R. Kolatkar*

IMCB-BIC, Institute of Molecular and Cell Biology, 30 Medical Drive, 117609 Singapore

Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVMlight. Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms.

* To whom correspondence should be addressed at present address: Genome Institute of Singapore, 1 Science Park Road, 05-01, The Capricorn, Singapore Science Park II, 117528 Singapore. Tel: +65 872 7552; Fax: +65 872 7447; Email: gisprk{at}nus.edu.sg Present addresses:Kui Lin, Yuyu Kuang and Jeremiah S. Joseph, Genome Institute of Singapore, 1 Science Park Road, 05-01, The Capricorn, Singapore Science Park II, 117528 Singapore


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