PHACTS, a computational approach to classifying the lifestyle of phages

Motivation: Bacteriophages have two distinct lifestyles: virulent and temperate. The virulent lifestyle has many implications for phage therapy, genomics and microbiology. Determining which lifestyle a newly sequenced phage falls into is currently determined using standard culturing techniques. Such laboratory work is not only costly and time consuming, but also cannot be used on phage genomes constructed from environmental sequencing. Therefore, a computational method that utilizes the sequence data of phage genomes is needed. Results: Phage Classification Tool Set (PHACTS) utilizes a novel similarity algorithm and a supervised Random Forest classifier to make a prediction whether the lifestyle of a phage, described by its proteome, is virulent or temperate. The similarity algorithm creates a training set from phages with known lifestyles and along with the lifestyle annotation, trains a Random Forest to classify the lifestyle of a phage. PHACTS predictions are shown to have a 99% precision rate. Availability and implementation: PHACTS was implemented in the PERL programming language and utilizes the FASTA program (Pearson and Lipman, 1988) and the R programming language library ‘Random Forest’ (Liaw and Weiner, 2010). The PHACTS software is open source and is available as downloadable stand-alone version or can be accessed online as a user-friendly web interface. The source code, help files and online version are available at http://www.phantome.org/PHACTS/. Contact: katelyn@rohan.sdsu.edu; redwards@sciences.sdsu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  Steve Labrie,et al.  Complete genomic sequence of bacteriophage ul36: demonstration of phage heterogeneity within the P335 quasi-species of lactococcal phages. , 2002, Virology.

[2]  Victor Ladero,et al.  The Dilemma of Phage Taxonomy Illustrated by Comparative Genomics of Sfi21-Like Siphoviridae in Lactic Acid Bacteria , 2002, Journal of bacteriology.

[3]  R. Hendrix,et al.  Evolutionary relationships among diverse bacteriophages and prophages: all the world's a phage. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Jaysheel D. Bhavsar,et al.  Phages across the biosphere: contrasts of viruses in soil and aquatic environments. , 2008, Research in microbiology.

[5]  Virus particle production in lysogenic bacteria exposed to protozoan grazing , 1998 .

[6]  R. Leplae,et al.  A modular view of the bacteriophage genomic space: identification of host and lifestyle marker modules. , 2011, Research in microbiology.

[7]  Armin Fiechter,et al.  Effects of growth medium on phage production and induction in Escherichia coli K-12 lambda lysogens , 1986 .

[8]  W. Whitman,et al.  Prokaryotes: the unseen majority. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Patrick Deschavanne,et al.  The use of genomic signature distance between bacteriophages and their hosts displays evolutionary relationships and phage growth cycle determination , 2010, Virology Journal.

[10]  E. Witkin.  Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli , 1976 .

[11]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .

[12]  G. Hatfull,et al.  Mycobacteriophage D29 integrase-mediated recombination: specificity of mycobacteriophage integration. , 1998, Gene.

[13]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Gipsi Lima-Mendez,et al.  Reticulate representation of evolutionary and functional relationships between phage genomes. , 2008, Molecular biology and evolution.

[15]  Forest Rohwer,et al.  Global Phage Diversity , 2003, Cell.

[16]  F. Twort,et al.  PHAGE THERAPY , 1983, The Lancet.

[17]  R. Edwards,et al.  The Phage Proteomic Tree: a Genome-Based Taxonomy for Phage , 2002, Journal of bacteriology.

[18]  K. Wommack,et al.  Virioplankton: Viruses in Aquatic Ecosystems , 2000, Microbiology and Molecular Biology Reviews.