title: PhylDiag: identifying complex synteny blocks that include tandem duplications using phylogenetic gene trees.
abstract: BACKGROUND
  Extant genomes share regions where genes have the same order and orientation, which are thought to arise from the conservation of an ancestral order of genes during evolution. Such regions of so-called conserved synteny, or synteny blocks, must be precisely identified and quantified, as a prerequisite to better understand the evolutionary history of genomes.
  
  
  RESULTS
  Here we describe PhylDiag, a software that identifies statistically significant synteny blocks in pairwise comparisons of eukaryote genomes. Compared to previous methods, PhylDiag uses gene trees to define gene homologies, thus allowing gene deletions to be considered as events that may break the synteny. PhylDiag also accounts for gene orientations, blocks of tandem duplicates and lineage specific de novo gene births. Starting from two genomes and the corresponding gene trees, PhylDiag returns synteny blocks with gaps less than or equal to the maximum gap parameter gap(max). This parameter is theoretically estimated, and together with a utility to graphically display results, contributes to making PhylDiag a user friendly method. In addition, putative synteny blocks are subject to a statistical validation to verify that they are unlikely to be due to a random combination of genes.
  
  
  CONCLUSIONS
  We benchmark several known metrics to measure 2D-distances in a matrix of homologies and we compare PhylDiag to i-ADHoRe 3.0 on real and simulated data. We show that PhylDiag correctly identifies small synteny blocks even with insertions, deletions, incorrect annotations or micro-inversions. Finally, PhylDiag allowed us to identify the most relevant distance metric for 2D-distance calculation between homologies.
authors.forename: Joseph M E X
authors.initials: JM
authors.lastname: Lucas
authors.forename: Matthieu
authors.initials: M
authors.lastname: Muffato
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, 46 rue d'Ulm, 75005 Paris, France. hrc@ens.fr.
authors.forename: Hugues
authors.initials: H
authors.lastname: Roest Crollius
mesh_terms: D000818:Animals; D020440:Gene Duplication; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D010802:Phylogeny; D012984:Software; D026801:Synteny
references.citation: Genome Res. 2006 Dec;16(12):1557-65
references.pmid: 16983148
references.citation: J Bioinform Comput Biol. 2008 Feb;6(1):1-22
references.pmid: 18324742
references.citation: Genome Res. 2006 Sep;16(9):1159-68
references.pmid: 16951135
references.citation: Comput Biol Chem. 2003 Feb;27(1):59-67
references.pmid: 12798040
references.citation: Genome Res. 2004 Jun;14(6):1095-106
references.pmid: 15173115
references.citation: J Mol Biol. 1981 Mar 25;147(1):195-7
references.pmid: 7265238
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D546-52
references.pmid: 24163254
references.citation: Bioinformatics. 2004 Dec 12;20(18):3643-6
references.pmid: 15247098
references.citation: Genome Res. 2008 Dec;18(12):1944-54
references.pmid: 18832442
references.citation: Science. 2005 Jul 22;309(5734):613-7
references.pmid: 16040707
references.citation: Nucleic Acids Res. 2012 Apr;40(7):e49
references.pmid: 22217600
references.citation: Genome Res. 2007 May;17(5):545-55
references.pmid: 17387144
references.citation: Genome Biol. 2003;4(10):R68
references.pmid: 14519203
references.citation: Algorithms Mol Biol. 2008 Nov 06;3:14
references.pmid: 18990215
references.citation: J Comput Biol. 2005 Oct;12(8):1083-102
references.pmid: 16241899
references.citation: Bioinformatics. 2005 Apr 15;21(8):1339-48
references.pmid: 15585535
references.citation: PLoS Comput Biol. 2008 Nov;4(11):e1000234
references.pmid: 19043541
references.citation: Bioinformatics. 2010 Oct 15;26(20):2509-16
references.pmid: 20736338
references.citation: Genome Res. 2009 Feb;19(2):327-35
references.pmid: 19029536
references.citation: Bioinformatics. 2005 Dec 1;21(23):4209-15
references.pmid: 16216829
references.citation: Genome Res. 2008 Mar;18(3):370-9
references.pmid: 18230801
references.citation: J Comput Biol. 2005 Jul-Aug;12(6):638-56
references.pmid: 16108708
references.citation: Mol Biol Evol. 2009 May;26(5):957-68
references.pmid: 19150803
references.citation: Genome Res. 2012 Dec;22(12):2356-67
references.pmid: 22722344
references.citation: Genome Res. 2008 Nov;18(11):1814-28
references.pmid: 18849524
references.citation: Bioinformatics. 2003;19 Suppl 1:i74-80
references.pmid: 12855440
references.citation: Genome Res. 2003 May;13(5):999-1010
references.pmid: 12695327
references.citation: Nucleic Acids Res. 2012 Jan;40(2):e11
references.pmid: 22102584
references.citation: BMC Bioinformatics. 2006 Oct 12;7:447
references.pmid: 17038171
references.citation: J Comput Biol. 2003;10(3-4):453-82
references.pmid: 12935338
references.citation: Bioinformatics. 2002 Mar;18(3):492-3
references.pmid: 11934753
references.citation: Bioinformatics. 2009 Mar 1;25(5):571-7
references.pmid: 19158161
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Genome Res. 2002 Nov;12(11):1792-801
references.pmid: 12421767
references.citation: BMC Bioinformatics. 2007 Mar 08;8:82
references.pmid: 17343765
references.citation: PLoS One. 2010 Jan 28;5(1):e8861
references.pmid: 20126624