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Open Access Methodology article

Comparison of codon usage measures and their applicability in prediction of microbial gene expressivity

Fran Supek1 and Kristian Vlahoviček12*

Author Affiliations

1 Department of Molecular Biology, Division of Biology, Faculty of Science, Zagreb University, Rooseveltov trg 6, 10000 Zagreb, Croatia

2 Protein Structure and Bioinformatics, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy

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BMC Bioinformatics 2005, 6:182  doi:10.1186/1471-2105-6-182

Published: 19 July 2005

Abstract

Background

There are a number of methods (also called: measures) currently in use that quantify codon usage in genes. These measures are often influenced by other sequence properties, such as length. This can introduce strong methodological bias into measurements; therefore we attempted to develop a method free from such dependencies. One of the common applications of codon usage analyses is to quantitatively predict gene expressivity.

Results

We compared the performance of several commonly used measures and a novel method we introduce in this paper – Measure Independent of Length and Composition (MILC). Large, randomly generated sequence sets were used to test for dependence on (i) sequence length, (ii) overall amount of codon bias and (iii) codon bias discrepancy in the sequences. A derivative of the method, named MELP (MILC-based Expression Level Predictor) can be used to quantitatively predict gene expression levels from genomic data. It was compared to other similar predictors by examining their correlation with actual, experimentally obtained mRNA or protein abundances.

Conclusion

We have established that MILC is a generally applicable measure, being resistant to changes in gene length and overall nucleotide composition, and introducing little noise into measurements. Other methods, however, may also be appropriate in certain applications. Our efforts to quantitatively predict gene expression levels in several prokaryotes and unicellular eukaryotes met with varying levels of success, depending on the experimental dataset and predictor used. Out of all methods, MELP and Rainer Merkl's GCB method had the most consistent behaviour. A 'reference set' containing known ribosomal protein genes appears to be a valid starting point for a codon usage-based expressivity prediction.