Research article

Models of deletion for visualizing bacterial variation: an application to tuberculosis spoligotypes

Josephine F Reyes^1,2 , Andrew R Francis³ and Mark M Tanaka^1,2

¹  School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia

²  Evolution & Ecology Research Centre, University of New South Wales, Sydney 2052, Australia

³  School of Computing and Mathematics, University of Western Sydney, South Penrith DC, NSW 1797, Australia

author email corresponding author email

BMC Bioinformatics 2008, 9:496doi:10.1186/1471-2105-9-496

Published:	27 November 2008

Abstract

Background

Molecular typing methods are commonly used to study genetic relationships among bacterial isolates. Many of these methods have become standardized and produce portable data. A popular approach for analyzing such data is to construct graphs, including phylogenies. Inferences from graph representations of data assist in understanding the patterns of transmission of bacterial pathogens, and basing these graph constructs on biological models of evolution of the molecular marker helps make these inferences. Spoligotyping is a widely used method for genotyping isolates of Mycobacterium tuberculosis that exploits polymorphism in the direct repeat region. Our goal was to examine a range of models describing the evolution of spoligotypes in order to develop a visualization method to represent likely relationships among M. tuberculosis isolates.

Results

We found that inferred mutations of spoligotypes frequently involve the loss of a single or very few adjacent spacers. Using a second-order variant of Akaike's Information Criterion, we selected the Zipf model as the basis for resolving ambiguities in the ancestry of spoligotypes. We developed a method to construct graphs of spoligotypes (which we call spoligoforests). To demonstrate this method, we applied it to a tuberculosis data set from Cuba and compared the method to some existing methods.

Conclusion

We propose a new approach in analyzing relationships of M. tuberculosis isolates using spoligotypes. The spoligoforest recovers a plausible history of transmission and mutation events based on the selected deletion model. The method may be suitable to study markers based on loci of similar structure from other bacteria. The groupings and relationships in the spoligoforest can be analyzed along with the clinical features of strains to provide an understanding of the evolution of spoligotypes.