Tetranucleotide usage in mycobacteriophage genomes: alignment-free methods to cluster phage and infer evolutionary relationships

Siranosian, Benjamin A.; Herold, Emma; Williams, Edward; Ye, Chen An; Graffenried, Christopher L. de

doi:10.1186/1471-2105-16-s2-a7

“…This program allows first year undergraduate students to isolate and characterize novel mycobacteriophages from the environment. It has also provided excellent opportunities for collaborative projects between undergraduates, resulting in the work presented here Siranosian et al (2015a) .…”

Section: Introductionmentioning

confidence: 99%

Tetranucleotide usage highlights genomic heterogeneity among mycobacteriophages

Siranosian

¹

,

Perera

²

,

Williams

³

et al. 2015

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Background The genomic sequences of mycobacteriophages, phages infecting mycobacterial hosts, are diverse and mosaic. Mycobacteriophages often share little nucleotide similarity, but most of them have been grouped into lettered clusters and further into subclusters. Traditionally, mycobacteriophage genomes are analyzed based on sequence alignment or knowledge of gene content. However, these approaches are computationally expensive and can be ineffective for significantly diverged sequences. As an alternative to alignment-based genome analysis, we evaluated tetranucleotide usage in mycobacteriophage genomes. These methods make it easier to characterize features of the mycobacteriophage population at many scales. Description We computed tetranucleotide usage deviation (TUD), the ratio of observed counts of 4-mers in a genome to the expected count under a null model. TUD values are comparable between members of a phage subcluster and distinct between subclusters. With few exceptions, neighbor joining phylogenetic trees and hierarchical clustering dendrograms constructed using TUD values place phages in a monophyletic clade with members of the same subcluster. Regions in a genome with exceptional TUD values can point to interesting features of genomic architecture. Finally, we found that subcluster B3 mycobacteriophages contain significantly overrepresented 4-mers and 6-mers that are atypical of phage genomes. Conclusions Statistics based on tetranucleotide usage support established clustering of mycobacteriophages and can uncover interesting relationships within and between sequenced phage genomes. These methods are efficient to compute and do not require sequence alignment or knowledge of gene content. The code to download mycobacteriophage genome sequences and reproduce our analysis is freely available at https://github.com/bsiranosian/tango_final.

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Highlights from the tenth ISCB Student Council Symposium 2014

Rahman

¹

,

Wilkins

²

,

Jacobsen³

et al. 2015

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Tetranucleotide usage highlights genomic heterogeneity among mycobacteriophages

Siranosian

¹

,

Perera

²

,

Williams

³

et al. 2015

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2

0

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Background The genomic sequences of mycobacteriophages, phages infecting mycobacterial hosts, are diverse and mosaic. Mycobacteriophages often share little nucleotide similarity, but most of them have been grouped into lettered clusters and further into subclusters. Traditionally, mycobacteriophage genomes are analyzed based on sequence alignment or knowledge of gene content. However, these approaches are computationally expensive and can be ineffective for significantly diverged sequences. As an alternative to alignment-based genome analysis, we evaluated tetranucleotide usage in mycobacteriophage genomes. These methods make it easier to characterize features of the mycobacteriophage population at many scales. Description We computed tetranucleotide usage deviation (TUD), the ratio of observed counts of 4-mers in a genome to the expected count under a null model. TUD values are comparable between members of a phage subcluster and distinct between subclusters. With few exceptions, neighbor joining phylogenetic trees and hierarchical clustering dendrograms constructed using TUD values place phages in a monophyletic clade with members of the same subcluster. Regions in a genome with exceptional TUD values can point to interesting features of genomic architecture. Finally, we found that subcluster B3 mycobacteriophages contain significantly overrepresented 4-mers and 6-mers that are atypical of phage genomes. Conclusions Statistics based on tetranucleotide usage support established clustering of mycobacteriophages and can uncover interesting relationships within and between sequenced phage genomes. These methods are efficient to compute and do not require sequence alignment or knowledge of gene content. The code to download mycobacteriophage genome sequences and reproduce our analysis is freely available at https://github.com/bsiranosian/tango_final.

show abstract

Tetranucleotide usage in mycobacteriophage genomes: alignment-free methods to cluster phage and infer evolutionary relationships

Cited by 3 publications

References 4 publications

Tetranucleotide usage highlights genomic heterogeneity among mycobacteriophages

Tetranucleotide usage highlights genomic heterogeneity among mycobacteriophages

Highlights from the tenth ISCB Student Council Symposium 2014

Tetranucleotide usage highlights genomic heterogeneity among mycobacteriophages

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