title: A universal genomic coordinate translator for comparative genomics.
abstract: BACKGROUND
  Genomic duplications constitute major events in the evolution of species, allowing paralogous copies of genes to take on fine-tuned biological roles. Unambiguously identifying the orthology relationship between copies across multiple genomes can be resolved by synteny, i.e. the conserved order of genomic sequences. However, a comprehensive analysis of duplication events and their contributions to evolution would require all-to-all genome alignments, which increases at N2 with the number of available genomes, N.
  
  
  RESULTS
  Here, we introduce Kraken, software that omits the all-to-all requirement by recursively traversing a graph of pairwise alignments and dynamically re-computing orthology. Kraken scales linearly with the number of targeted genomes, N, which allows for including large numbers of genomes in analyses. We first evaluated the method on the set of 12 Drosophila genomes, finding that orthologous correspondence computed indirectly through a graph of multiple synteny maps comes at minimal cost in terms of sensitivity, but reduces overall computational runtime by an order of magnitude. We then used the method on three well-annotated mammalian genomes, human, mouse, and rat, and show that up to 93% of protein coding transcripts have unambiguous pairwise orthologous relationships across the genomes. On a nucleotide level, 70 to 83% of exons match exactly at both splice junctions, and up to 97% on at least one junction. We last applied Kraken to an RNA-sequencing dataset from multiple vertebrates and diverse tissues, where we confirmed that brain-specific gene family members, i.e. one-to-many or many-to-many homologs, are more highly correlated across species than single-copy (i.e. one-to-one homologous) genes. Not limited to protein coding genes, Kraken also identifies thousands of newly identified transcribed loci, likely non-coding RNAs that are consistently transcribed in human, chimpanzee and gorilla, and maintain significant correlation of expression levels across species.
  
  
  CONCLUSIONS
  Kraken is a computational genome coordinate translator that facilitates cross-species comparisons, distinguishes orthologs from paralogs, and does not require costly all-to-all whole genome mappings. Kraken is freely available under LPGL from http://github.com/nedaz/kraken.
authors: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. neda.zamani@imbim.uu.se.
authors: Neda
authors: N
authors: Zamani
authors: Görel
authors: G
authors: Sundström
authors: Jennifer R S
authors: JR
authors: Meadows
authors: Marc P
authors: MP
authors: Höppner
authors: Jacques
authors: J
authors: Dainat
authors: Henrik
authors: H
authors: Lantz
authors: Brian J
authors: BJ
authors: Haas
authors: Manfred G
authors: MG
authors: Grabherr
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D051381:Rats; D012984:Software; D026801:Synteny / Q000235:genetics; D014158:Transcription, Genetic