Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

BackgroundIdentifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes.ResultsWe present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance). In particular, Cinteny provides: i) integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii) flexibility to adjust the parameters and re-compute the results on-the-fly; iii) ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org.ConclusionCinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances. Cinteny can also be used to interactively browse syntenic blocks conserved in multiple genomes, to facilitate genome annotation and validation of assemblies for newly sequenced genomes, and to construct and assess phylogenomic trees.

[1]  Pavel A. Pevzner,et al.  Transforming men into mice (polynomial algorithm for genomic distance problem) , 1995, Proceedings of IEEE 36th Annual Foundations of Computer Science.

[2]  Robert Sedgewick,et al.  Fast algorithms for sorting and searching strings , 1997, SODA '97.

[3]  David A. Bader,et al.  A New Implmentation and Detailed Study of Breakpoint Analysis , 2000, Pacific Symposium on Biocomputing.

[4]  Lincoln Stein,et al.  Synbrowse: a Synteny Browser for Comparative Sequence Analysis , 2022 .

[5]  P. Pevzner,et al.  Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. , 2004, Genome research.

[6]  Pavel A Pevzner,et al.  The Fragile Breakage versus Random Breakage Models of Chromosome Evolution , 2006, PLoS Comput. Biol..

[7]  Glenn Tesler,et al.  GRIMM: genome rearrangements web server , 2002, Bioinform..

[8]  J. Nadeau,et al.  Lengths of chromosomal segments conserved since divergence of man and mouse. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Alistair G. Rust,et al.  Ensembl 2002: accommodating comparative genomics , 2003, Nucleic Acids Res..

[10]  Leonid Peshkin,et al.  Roundup: a multi-genome repository of orthologs and evolutionary distances , 2006, Bioinform..

[11]  David Sankoff,et al.  Conserved segment identification , 1997, RECOMB '97.

[12]  P. Pevzner,et al.  Genome rearrangements in mammalian evolution: lessons from human and mouse genomes. , 2003, Genome research.

[13]  F Galibert,et al.  Detailed four-way comparative mapping and gene order analysis of the canine ctvm locus reveals evolutionary chromosome rearrangements. , 2004, Genomics.

[14]  D. Church,et al.  Cross-species sequence comparisons: a review of methods and available resources. , 2003, Genome research.

[15]  D. Eisenberg,et al.  Detecting protein function and protein-protein interactions from genome sequences. , 1999, Science.

[16]  David A. Bader,et al.  A Linear-Time Algorithm for Computing Inversion Distance between Signed Permutations with an Experimental Study , 2001, WADS.

[17]  S. Lewis,et al.  The generic genome browser: a building block for a model organism system database. , 2002, Genome research.

[18]  BMC Bioinformatics , 2005 .

[19]  David Haussler,et al.  Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution. , 2003, Genome research.