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Cited by 147Genomics and Phylogenetic StudiesGenome Rearrangement AlgorithmsChromosomal and Genetic Variations

Inferring synteny between genome assemblies: a systematic evaluation

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Liu, Dang, Hunt, Martin, Tsai, Isheng J·2018·BMC Bioinformatics
DOI 10.1186/s12859-018-2026-4PMC PMC5791376

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Abstract

Abstract Identification of synteny between genomes of closely related species is an important aspect of comparative genomics. However, it is unknown to what extent draft assemblies lead to errors in such analysis. To investigate this, we fragmented genome assemblies of model nematodes to various extents and conducted synteny identification and downstream analysis. We first show that synteny between species can be underestimated up to 40% and find disagreements between popular tools that infer synteny blocks. This inconsistency and further demonstration of erroneous gene ontology enrichment tests throws into question the robustness of previous synteny analysis when gold standard genome sequences remain limited. In addition, determining the true evolutionary relationship is compromised by assembly improvement using a reference guided approach with a closely related species. Annotation quality, however, has minimal effect on synteny if the assembled genome is highly contiguous. Our results highlight the need for gold standard genome assemblies for synteny identification and accurate downstream analysis. Author summary Genome assemblies across all domains of life are currently produced routinely. Initial analysis of any new genome usually includes annotation and comparative genomics. Synteny provides a framework in which conservation of homologous genes and gene order is identified between genomes of different species. The availability of human and mouse genomes paved the way for algorithm development in large-scale synteny mapping, which eventually became an integral part of comparative genomics. Synteny analysis is regularly performed on assembled sequences that are fragmented, neglecting the fact that most methods were developed using complete genomes. Here, we systematically evaluate this interplay by inferring synteny in genome assemblies with different degrees of contiguation. As expected, our investigation reveals that assembly quality can drastically affect synteny analysis, from the initial synteny identification to downstream analysis. Importantly, we found that improving a fragmented assembly using synteny with the genome of a related species can be dangerous, as this a priori assumes a potentially false evolutionary relationship between the species. The results presented here re-emphasize the importance of gold standard genomes to the science community, and should be achieved given the current progress in sequencing technology.

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  1. [1]Gordon D Huddleston J Chaisson MJ Hill CM Kronenberg ZN Munson KM Malig M Raja A Fiddes I Hillier LW Long-read sequence assembly of the gorilla genome Science (New York, NY) 2016 352 aae0344 10.1126/science.aae0344 PMC4920363 27034376 · DOI · Paper page
  2. [2]Lien S Koop BF Sandve SR Miller JR Matthew P Leong JS Minkley DR Zimin A Grammes F Grove H The Atlantic salmon genome provides insights into rediploidization Nature 2016 533 200 205 10.1038/nature17164 27088604 PMC8127823 · DOI
  3. [3]Iorizzo M, Ellison S, Senalik D, Zeng P, Satapoomin P, Huang J, Bowman M, Iovene M, Sanseverino W, Cavagnaro P, et al. A high-quality carrot genome assembly provides new insights into carotenoid accumulation and asterid genome evolution. Nat Genet. 2016;48:657–66. 27158781
  4. [4]Jarvis DE, Ho YS, Lightfoot DJ, Schmöckel SM, Li B, Borm TJA, Ohyanagi H, Mineta K, Michell CT, Saber N, et al. The genome of Chenopodium Quinoa. Nature. 2017;542:1-6. 28178233
  5. [5]Ma L Chen Z Huang DW Kutty G Ishihara M Wang H Abouelleil A Bishop L Davey E Deng R Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts Nat Commun 2016 7 10740 10.1038/ncomms10740 26899007 PMC4764891 · DOI
  6. [6]de Man TJB Stajich JE Kubicek CP Teiling C Chenthamara K Atanasova L Druzhinina IS Levenkova N SSL B Barribeau SM Small genome of the fungus Escovopsis weberi, a specialized disease agent of ant agriculture Proc Natl Acad Sci 2016 113 3567 3572 10.1073/pnas.1518501113 26976598 PMC4822581 · DOI
  7. [7]Hunt VL Tsai IJ Coghlan A Reid AJ Holroyd N Foth BJ Tracey A Cotton JA Stanley EJ Beasley H The genomic basis of parasitism in the Strongyloides clade of nematodes Nat Genet 2016 48 299 307 10.1038/ng.3495 26829753 PMC4948059 · DOI
  8. [8]Cotton JA Bennuru S Grote A Harsha B Tracey A Beech R Doyle SR Dunn M JCD H Holroyd N The genome of Onchocerca volvulus, agent of river blindness Nat Microbiol 2016 2 16216 10.1038/nmicrobiol.2016.216 27869790 PMC5310847 · DOI
  9. [9]Chen X Tompa M Comparative assessment of methods for aligning multiple genome sequences Nat Biotechnol 2010 28 567 572 10.1038/nbt.1637 20495551 · DOI
  10. [11]Treangen TJ Salzberg SL Repetitive DNA and next-generation sequencing: computational challenges and solutions Nat Rev Genet 2012 46 36 46 10.1038/nrg3117 PMC3324860 22124482 · DOI
  11. [12]Uricaru R Michotey C Chiapello H Rivals E YOC, a new strategy for pairwise alignment of collinear genomes BMC Bioinf 2015 16 111 10.1186/s12859-015-0530-3 PMC4411659 25885358 · DOI
  12. [13]Ehrlich J, Sankoff D, Nadeau JH: Synteny conservation and chromosome rearrangements during mammalian evolution. Genetics 1997, 296:289-296. PMC1208112 9286688
  13. [14]Ghiurcuta CG BME M Evaluating synteny for improved comparative studies Bioinformatics 2014 30 9 18 10.1093/bioinformatics/btu259 24932010 PMC4058928 · DOI
  14. [15]Renwick JH The mapping of human chromosome Annu Rev Genet 1971 5 81 120 10.1146/annurev.ge.05.120171.000501 16097652 · DOI
  15. [16]Nadeau JH. Maps of linkage and synteny homologies between mouse and man. Trends Genet. 1989;5:82—6. 2660365
  16. [17]Vergara IA Chen N Large synteny blocks revealed between Caenorhabditis Elegans and Caenorhabditis Briggsae genomes using OrthoCluster BMC Genomics 2010 11 516 10.1186/1471-2164-11-516 20868500 PMC2997010 · DOI
  17. [18]Tang H, Lyons E, Pedersen B, Schnable JC, Paterson AH, Freeling M. Screening synteny blocks in pairwise genome comparisons through integer programming. BMC Bioinformatics. 2011:1-11. PMC3088904 21501495
  18. [19]Schmidt R Synteny - recent advances and future prospects Curr Opin Plant Biol 2000 3 97 102 10.1016/S1369-5266(99)00048-5 10712952 · DOI
  19. [20]Vandepoele K Saeys Y Simillion C Raes J Van de Peer Y The automatic detection of homologous regions (ADHoRe) and its application to microcolinearity between Arabidopsis and rice Genome Res 2002 12 1792 1801 10.1101/gr.400202 12421767 PMC187543 · DOI
  20. [21]Coghlan A Eichler EE Oliver SG Paterson AH Stein L Chromosome evolution in eukaryotes: a multi-kingdom perspective Trends Genet 2005 21 673 682 10.1016/j.tig.2005.09.009 16242204 · DOI
  21. [22]Molinari NA, Petrov DA, Price HJ, Smith JD, Gold JR, Vassiliadis C, Dudley JW, Biradar DP, Devos KM, Bennetzen JL, et al. Synteny and collinearity in plant genomes. Science. 2008;320(5875):486—8. 18436778
  22. [23]Zhang G Li B Li C MTP G Jarvis ED Wang J Comparative genomic data of the avian Phylogenomics project GigaScience 2014 3 26 10.1186/2047-217X-3-26 25671091 PMC4322804 · DOI
  23. [24]Howe KL Bolt BJ Cain S Chan J Chen WJ Davis P Done J Down T Gao S Grove C WormBase 2016: expanding to enable helminth genomic research Nucleic Acids Res 2016 44 D774 D780 10.1093/nar/gkv1217 26578572 PMC4702863 · DOI
  24. [25]C. elegans Sequencing Consortium TCeS Fleischmann RD Bult CJ Goffeau A Coulson AR Coulson A Coulson A Greenwald I Coulson A Sulston J Genome sequence of the nematode C. Elegans: a platform for investigating biology Science (New York, NY) 1998 282 2012 2018 10.1126/science.282.5396.2012 9851916 · DOI
  25. [26]Stein LD Bao Z Blasiar D Blumenthal T Brent MR Chen N Chinwalla A Clarke L Clee C Coghlan A The genome sequence of Caenorhabditis Briggsae: a platform for comparative genomics PLoS Biol 2003 1 E45 10.1371/journal.pbio.0000045 14624247 PMC261899 · DOI
  26. [27]Wong S Wolfe KH Birth of a metabolic gene cluster in yeast by adaptive gene relocation Nat Genet 2005 37 777 782 10.1038/ng1584 15951822 · DOI
  27. [28]Luebeck G Genomic evolution of metastasis.Editorial Nature 2010 467 1053 1054 10.1038/4671053a 20981088 · DOI
  28. [29]Ruelens P de Maagd RA Proost S Theißen G Geuten K Kaufmann K FLOWERING LOCUS C in monocots and the tandem origin of angiosperm-specific MADS-box genes Nat Commun 2013 4 2280 10.1038/ncomms3280 23955420 · DOI
  29. [30]Kemkemer C Kohn M Cooper DN Froenicke L Högel J Hameister H Kehrer-Sawatzki H Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution BMC Evol Biol 2009 9 84 10.1186/1471-2148-9-84 19393055 PMC2681463 · DOI
  30. [31]Murat F Armero A Pont C Klopp C Salse J Reconstructing the genome of the most recent common ancestor of flowering plants Nat Genet 2017 49 490 496 10.1038/ng.3813 28288112 · DOI
  31. [32]Denton JF, Lugo-Martinez J, Tucker AE, Schrider DR, Warren WC, Hahn MW. Extensive Error in the Number of Genes Inferred from Draft Genome Assemblies. PLoS Comput Biol. 2014;10(12):e1003998. PMC4256071 25474019
  32. [33]Dupont P-Y Cox MP Genomic data quality impacts automated detection of lateral gene transfer in fungi G3 (Bethesda, Md) 2017 7 g3.116.038448 PMC5386878 28235827
  33. [34]Batzoglou S The many faces of sequence alignment Brief Bioinform 2005 6 6 22 10.1093/bib/6.1.6 15826353 · DOI
  34. [36]Grabherr MG Russell P Meyer M Mauceli E Alföldi J di Palma F Lindblad-Toh K Genome-wide synteny through highly sensitive sequence alignment: Satsuma Bioinformatics 2010 26 1145 1151 10.1093/bioinformatics/btq102 20208069 PMC2859124 · DOI · Paper page
  35. [37]Haas BJ Delcher AL Wortman JR Salzberg SL DAGchainer: a tool for mining segmental genome duplications and synteny Bioinformatics 2004 20 3643 3646 10.1093/bioinformatics/bth397 15247098 · DOI · Paper page
  36. [38]Wang Y Tang H Debarry JD Tan X Li J Wang X Lee TH Jin H Marler B Guo H MCScanX: a toolkit for detection and evolutionary analysis of gene synteny and collinearity Nucleic Acids Res 2012 40 1 14 10.1093/nar/gkr648 22217600 PMC3326336 · DOI
  37. [39]Proost S Fostier J De Witte D Dhoedt B Demeester P Van De Peer Y Vandepoele K I-ADHoRe 3.0-fast and sensitive detection of genomic homology in extremely large data sets Nucleic Acids Res 2012 40 1 11 10.1093/nar/gkr955 22102584 PMC3258164 · DOI
  38. [40]Drillon G Carbone A Fischer G SynChro: a fast and easy tool to reconstruct and visualize synteny blocks along eukaryotic chromosomes PLoS One 2014 9 1 8 10.1371/journal.pone.0092621 PMC3961402 24651407 · DOI
  39. [41]Ross JA, Koboldt DC, Staisch JE, Chamberlin HM, Gupta BP, Miller RD, Baird SE, Haag ES. Caenorhabditis Briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination. PLoS Genet. 2011;7(7):e1002174. PMC3136444 21779179
  40. [42]Bhutkar A Russo S Smith TF Gelbart WM Techniques for multi-genome synteny analysis to overcome assembly limitations Genome Inform Int Conference Genome Inform 2006 17 152 161 17503388
  41. [43]Goodwin S McPherson JD McCombie WR Coming of age: ten years of next-generation sequencing technologies Nat Rev Genet 2016 17 333 351 10.1038/nrg.2016.49 27184599 PMC10373632 · DOI · Paper page
  42. [44]Treangen TJ Ondov BD Koren S Phillippy AM The harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes Genome Biol 2014 15 524 10.1186/s13059-014-0524-x 25410596 PMC4262987 · DOI
  43. [45]Viney ME The biology and genomics of Strongyloides Med Microbiol Immunol 2006 195 49 54 10.1007/s00430-006-0013-2 16538445 · DOI
  44. [46]Ward JD Rendering the intractable more tractable: tools from caenorhabditis elegans ripe for import into parasitic nematodes Genetics 2015 201 1279 1294 10.1534/genetics.115.182717 26644478 PMC4676526 · DOI
  45. [47]Armengol L Marquès-Bonet T Cheung J Khaja R González JR Scherer SW Navarro A Estivill X Murine segmental duplications are hot spots for chromosome and gene evolution Genomics 2005 86 692 700 10.1016/j.ygeno.2005.08.008 16256303 · DOI
  46. [48]Davidson RM Gowda M Moghe G Lin H Vaillancourt B Shiu SH Jiang N Robin Buell C Comparative transcriptomics of three Poaceae species reveals patterns of gene expression evolution Plant J 2012 71 492 502 22443345
  47. [49]Lovell PV, Wirthlin M, Wilhelm L, Minx P, Lazar NH, Carbone L, Warren WC, Mello CV. Conserved syntenic clusters of protein coding genes are missing in birds. Genome Biol. 2014;15(565):1—27. PMC4290089 25518852
  48. [50]Baldauf J Marcon C Paschold A Hochholdinger F Nonsyntenic genes drive tissue-specific dynamics of differential, nonadditive and allelic expression patterns in maize hybrids Plant Physiol 2016 171 00262.02016 PMC4902609 27208302
  49. [51]Assefa S Keane TM Otto TD Newbold C Berriman M ABACAS: algorithm-based automatic contiguation of assembled sequences Bioinformatics 2009 25 1968 1969 10.1093/bioinformatics/btp347 19497936 PMC2712343 · DOI
  50. [52]Husemann P Stoye J r2cat: Synteny plots and comparative assembly Bioinformatics 2009 26 570 571 10.1093/bioinformatics/btp690 20015948 PMC2820676 · DOI
  51. [53]Tang H Zhang X Miao C Zhang J Ming R Schnable JC Schnable PS Lyons E Lu J ALLMAPS: robust scaffold ordering based on multiple maps Genome Biol 2015 16 3 10.1186/s13059-014-0573-1 25583564 PMC4305236 · DOI
  52. [54]Stanke M Waack S Gene prediction with a hidden Markov model and a new intron submodel Bioinformatics 2003 19 215 225 10.1093/bioinformatics/btg1080 14534192 · DOI
  53. [55]Simão FA Waterhouse RM Ioannidis P Kriventseva EV BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs Genome Anal 2015 31 9 10 26059717
  54. [56]Hillier LW Miller RD Baird SE Chinwalla A Fulton LA Koboldt DC Waterston RH Comparison of C. Elegans and C. Briggsae genome sequences reveals extensive conservation of chromosome organization and synteny PLoS Biol 2007 5 1603 1616 10.1371/journal.pbio.0050167 PMC1914384 17608563 · DOI
  55. [57]Dudchenko O Batra SS Omer AD Nyquist SK Hoeger M Durand NC Shamim MS Machol I Lander ES Aiden AP De novo assembly of the Aedes Aegypti genome using hi-C yields chromosome-length scaffolds Science 2017 356 92 95 10.1126/science.aal3327 28336562 PMC5635820 · DOI
  56. [58]PSG C Grafham DV Fulton RS Fitzgerald MG Hostetler J Muzny D Ali J Birren B Bruce DC Buhay C Genome project standards in a new era of sequencing Science (New York, NY) 2009 326 4 5 PMC3854948 19815760
  57. [59]Thompson PC, Zarlenga DS, Liu M-Y, Rosenthal BM. Long-read sequencing improves assembly of Trichinella genomes 10-fold, revealing substantial synteny between lineages diverged over 7 million years. Parasitology. 2017;144(10):1—14. 28583210
  58. [60]Emms DM Kelly S OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy Genome Biol 2015 16 157 10.1186/s13059-015-0721-2 26243257 PMC4531804 · DOI · Paper page
  59. [61]Krzywinski M Schein J Birol I Connors J Gascoyne R Horsman D Jones SJ Marra MA Circos: an information esthetic for comparative genomics Genome Res 2009 19 1639 1645 10.1101/gr.092759.109 19541911 PMC2752132 · DOI

Cited by

Sorted by citations

Authors
Liu, D., Hunt, M., & Tsai, I. J.
Affiliations
  • National Taiwan University (TW)
  • European Bioinformatics Institute (GB)
Corresponding author
Tsai, Isheng J
ORCID
Venue
BMC Bioinformatics
Publisher
Springer Science and Business Media LLC
Published
2018-01-30
Volume
19
Issue
1
Pages
26-26
ISSN
1471-2105 (ISSN-L)
DOI
10.1186/s12859-018-2026-4
PMC
PMC5791376
OpenAlex
W2952105401
Cited by
147
References
2
Citations by year
2026: 16 · 2025: 19 · 2024: 25 · 2023: 17 · 2022: 16 · 2021: 23 · 2020: 16 · 2019: 11 · 2018: 4
FWCI
4.72
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Bioinformatics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Academia Sinica
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
genome assembly, draft genome assembly, gene ontology enrichment, assembly contiguity, comparative genomics, annotation quality
MeSH terms
Algorithms, Animals, Nematoda, Genome, Caenorhabditis elegans, Genomics

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