title: Aligning the unalignable: bacteriophage whole genome alignments.
abstract: BACKGROUND
  In recent years, many studies focused on the description and comparison of large sets of related bacteriophage genomes. Due to the peculiar mosaic structure of these genomes, few informative approaches for comparing whole genomes exist: dot plots diagrams give a mostly qualitative assessment of the similarity/dissimilarity between two or more genomes, and clustering techniques are used to classify genomes. Multiple alignments are conspicuously absent from this scene. Indeed, whole genome aligners interpret lack of similarity between sequences as an indication of rearrangements, insertions, or losses. This behavior makes them ill-prepared to align bacteriophage genomes, where even closely related strains can accomplish the same biological function with highly dissimilar sequences.
  
  
  RESULTS
  In this paper, we propose a multiple alignment strategy that exploits functional collinearity shared by related strains of bacteriophages, and uses partial orders to capture mosaicism of sets of genomes. As classical alignments do, the computed alignments can be used to predict that genes have the same biological function, even in the absence of detectable similarity. The Alpha aligner implements these ideas in visual interactive displays, and is used to compute several examples of alignments of Staphylococcus aureus and Mycobacterium bacteriophages, involving up to 29 genomes. Using these datasets, we prove that Alpha alignments are at least as good as those computed by standard aligners. Comparison with the progressive Mauve aligner - which implements a partial order strategy, but whose alignments are linearized - shows a greatly improved interactive graphic display, while avoiding misalignments.
  
  
  CONCLUSIONS
  Multiple alignments of whole bacteriophage genomes work, and will become an important conceptual and visual tool in comparative genomics of sets of related strains. A python implementation of Alpha, along with installation instructions for Ubuntu and OSX, is available on bitbucket (https://bitbucket.org/thekswenson/alpha).
authors.affiliation: ISEM, CNRS - Univ. Montpellier, Montpellier, France. severine.berard@univ-montp2.fr.|LIRMM, CNRS - Univ. Montpellier, 161 rue Ada, Montpellier, 34392, France. severine.berard@univ-montp2.fr.
authors.forename: Sèverine
authors.initials: S
authors.lastname: Bérard
authors.affiliation: LIRMM, CNRS - Univ. Montpellier, 161 rue Ada, Montpellier, 34392, France. annie.chateau@gmail.com.|IBC Institut de Biologie Computationnelle, Montpellier, France. annie.chateau@gmail.com.
authors.forename: Annie
authors.initials: A
authors.lastname: Chateau
authors.affiliation: LIRMM, CNRS - Univ. Montpellier, 161 rue Ada, Montpellier, 34392, France. nicolas.pompidor@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pompidor
authors.affiliation: LaCIM, Université du Québec à Montréal, Montréal, Canada. pguertin@grasset.qc.ca.|Département de mathématiques, Collège André-Grasset, Montréal, Canada. pguertin@grasset.qc.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Guertin
authors.affiliation: LaCIM, Université du Québec à Montréal, Montréal, Canada. bergeron.anne@uqam.ca.
authors.forename: Anne
authors.initials: A
authors.lastname: Bergeron
authors.affiliation: LIRMM, CNRS - Univ. Montpellier, 161 rue Ada, Montpellier, 34392, France. swenson@lirmm.fr.|IBC Institut de Biologie Computationnelle, Montpellier, France. swenson@lirmm.fr.
authors.forename: Krister M
authors.initials: KM
authors.lastname: Swenson
mesh_terms: D000465:Algorithms; D001435:Bacteriophages / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D016679:Genome, Viral; D023281:Genomics / Q000379:methods; D009161:Mycobacterium / Q000821:virology*; D016415:Sequence Alignment / Q000379:methods*; D013211:Staphylococcus aureus / Q000821:virology*