For best viewing of the website please use Mozilla Firefox or Google Chrome.
Citation: Xiao Ding, Luyao Qin, Jing Meng, Yousong Peng, Aiping Wu, Taijiao Jiang. Progress and Challenge in Computational Identification of Influenza Virus Reassortment [J].VIROLOGICA SINICA, 2021, 36(6) : 1273-1283.  http://dx.doi.org/10.1007/s12250-021-00392-w

Progress and Challenge in Computational Identification of Influenza Virus Reassortment

  • Corresponding author: Taijiao Jiang, taijiao@ibms.pumc.edu.cn, ORCID: 0000-0002-6071-0122
  • Received Date: 03 September 2020
    Accepted Date: 29 March 2021
    Published Date: 26 May 2021
    Available online: 01 December 2021
  • Genomic reassortment is an important evolutionary mechanism for influenza viruses. In this process, the novel viruses acquire new characteristics by the exchange of the intact gene segments among multiple influenza virus genomes, which may cause flu endemics and epidemics within or even across hosts. Due to the safety and ethical limitations of the experimental studies on influenza virus reassortment, numerous computational researches on the influenza virus reassortment have been done with the explosion of the influenza virus genomic data. A great amount of computational methods and bioinformatics databases were developed to facilitate the identification of influenza virus reassortments. In this review, we summarized the progress and challenge of the bioinformatics research on influenza virus reassortment, which can guide the researchers to investigate the influenza virus reassortment events reasonably and provide valuable insight to develop the related computational identification tools.


  • 加载中
    1. Ahasan MS, Subramaniam K, Sayler KA, Loeb JC, Popov VL, Lednicky JA, Wisely SM, Campos Krauer JM, Waltzek TB (2019) Molecular characterization of a novel reassortment Mammalian orthoreovirus type 2 isolated from a Florida white-tailed deer fawn. Virus Res 270: 197642
        doi: 10.1016/j.virusres.2019.197642

    2. Arenas M, Posada D (2010) The effect of recombination on the reconstruction of ancestral sequences. Genetics 184: 1133-1139
        doi: 10.1534/genetics.109.113423

    3. Bi Y, Chen Q, Wang Q, Chen J, Jin T, Wong G, Quan C, Liu J, Wu J, Yin R, Zhao L, Li M, Ding Z, Zou R, Xu W, Li H, Wang H, Tian K, Fu G, Huang Y, Shestopalov A, Li S, Xu B, Yu H, Luo T, Lu L, Xu X, Luo Y, Liu Y, Shi W, Liu D, Gao GF (2016) Genesis, evolution and prevalence of H5N6 avian influenza viruses in China. Cell Host Microbe 20: 810-821
        doi: 10.1016/j.chom.2016.10.022

    4. Blitvich BJ, Saiyasombat R, Dorman KS, Garcia-Rejon JE, Farfan-Ale JA, Loroño-Pino MA (2012) Sequence and phylogenetic data indicate that an orthobunyavirus recently detected in the Yucatan Peninsula of Mexico is a novel reassortant of Potosi and Cache Valley viruses. Arch Virol 157: 1199-1204
        doi: 10.1007/s00705-012-1279-x

    5. Boni MF, de Jong MD, van Doorn HR, Holmes EC (2010) Guidelines for identifying homologous recombination events in influenza A virus. PLoS ONE 5: e10434
        doi: 10.1371/journal.pone.0010434

    6. Butler D (2011) Fears grow over lab-bred flu. Nature 480: 421-422
        doi: 10.1038/480421a

    7. Chan JM, Carlsson G, Rabadan R (2013) Topology of viral evolution. Proc Natl Acad Sci USA 110: 18566-18571
        doi: 10.1073/pnas.1313480110

    8. de Silva UC, Tanaka H, Nakamura S, Goto N, Yasunaga T (2012) A comprehensive analysis of reassortment in influenza A virus. Biol Open 1: 385-390
        doi: 10.1242/bio.2012281

    9. Ding X, Yuan X, Mao L, Wu A, Jiang T (2020) FluReassort: a database for the study of genomic reassortments among influenza viruses. Brief Bioinform 21: 2126-2132
        doi: 10.1093/bib/bbz128

    10. Dong C, Ying L, Yuan D (2011) Detecting transmission and reassortment events for influenza A viruses with genotype profile method. Virol J 8: 395
        doi: 10.1186/1743-422X-8-395

    11. Felsenstein J (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17: 368-376
        doi: 10.1007/BF01734359

    12. Fouchier RA (2015) Studies on influenza virus transmission between ferrets: the public health risks revisited. mBio 6: e02560-14

    13. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y (2013) Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368: 1888-1897
        doi: 10.1056/NEJMoa1304459

    14. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu X, Skepner E, Deyde V, Okomo-Adhiambo M, Gubareva L, Barnes J, Smith CB, Emery SL, Hillman MJ, Rivailler P, Smagala J, de Graaf M, Burke DF, Fouchier RA, Pappas C, Alpuche-Aranda CM, Lopez-Gatell H, Olivera H, Lopez I, Myers CA, Faix D, Blair PJ, Yu C, Keene KM, Dotson PD Jr, Boxrud D, Sambol AR, Abid SH, St George K, Bannerman T, Moore AL, Stringer DJ, Blevins P, Demmler-Harrison GJ, Ginsberg M, Kriner P, Waterman S, Smole S, Guevara HF, Belongia EA, Clark PA, Beatrice ST, Donis R, Katz J, Finelli L, Bridges CB, Shaw M, Jernigan DB, Uyeki TM, Smith DJ, Klimov AI, Cox NJ (2009) Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325: 197-201
        doi: 10.1126/science.1176225

    15. Goloboff PA, Wilkinson M (2018) On defining a unique phylogenetic tree with homoplastic characters. Mol Phylogenet Evol 122: 95-101
        doi: 10.1016/j.ympev.2018.01.020

    16. Graybeal A (1998) Is it better to add taxa or characters to a difficult phylogenetic problem? Syst Biol 47: 9-17
        doi: 10.1080/106351598260996

    17. Karasin AI, Carman S, Olsen CW (2006) Identification of human H1N2 and human-swine reassortant H1N2 and H1N1 influenza A viruses among pigs in Ontario, Canada (2003 to 2005). J Clin Microbiol 44: 1123-1126
        doi: 10.1128/JCM.44.3.1123-1126.2006

    18. Karasin AI, Landgraf J, Swenson S, Erickson G, Goyal S, Woodruff M, Scherba G, Anderson G, Olsen CW (2002) Genetic characterization of H1N2 influenza A viruses isolated from pigs throughout the United States. J Clin Microbiol 40: 1073-1079
        doi: 10.1128/JCM.40.3.1073-1079.2002

    19. Karasin AI, Schutten MM, Cooper LA, Smith CB, Subbarao K, Anderson GA, Carman S, Olsen CW (2000) Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977-1999: evidence for wholly human and reassortant virus genotypes. Virus Res 68: 71-85
        doi: 10.1016/S0168-1702(00)00154-4

    20. Kawaoka Y, Krauss S, Webster RG (1989) Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 63: 4603-4608
        doi: 10.1128/jvi.63.11.4603-4608.1989

    21. Keane TM, Creevey CJ, Pentony MM, Naughton TJ, McLnerney JO (2006) Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 6: 29
        doi: 10.1186/1471-2148-6-29

    22. Khiabanian H, Trifonov V, Rabadan R (2009) Reassortment patterns in Swine influenza viruses. PLoS ONE 4: e7366
        doi: 10.1371/journal.pone.0007366

    23. Kilbourne ED (2006) Influenza pandemics of the 20th century. Emerg Infect Dis 12: 9-14
        doi: 10.3201/eid1201.051254

    24. Kingsford C, Nagarajan N, Salzberg SL (2009) 2009 Swine-origin influenza A (H1N1) resembles previous influenza isolates. PLoS ONE 4: e6402
        doi: 10.1371/journal.pone.0006402

    25. Lam TT, Wang J, Shen Y, Zhou B, Duan L, Cheung CL, Ma C, Lycett SJ, Leung CY, Chen X, Li L, Hong W, Chai Y, Zhou L, Liang H, Ou Z, Liu Y, Farooqui A, Kelvin DJ, Poon LL, Smith DK, Pybus OG, Leung GM, Shu Y, Webster RG, Webby RJ, Peiris JS, Rambaut A, Zhu H, Guan Y (2013) The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 502: 241-244
        doi: 10.1038/nature12515

    26. Levin S, Holmes EC, Ghedin E, Miller N, Taylor J, Bao Y, St George K, Grenfell BT, Salzberg SL, Fraser CM, Lipman DJ, Taubenberger JK (2005) Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses. PLoS Biol 3: e300
        doi: 10.1371/journal.pbio.0030300

    27. Li YW, Yu L, Zhang YP (2007) "Long-branch Attraction" artifact in phylogenetic reconstruction. Yi Chuan 29: 659-667
        doi: 10.1360/yc-007-0659

    28. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73: 152-160
        doi: 10.1128/JVI.73.1.152-160.1999

    29. Lu G, Rowley T, Garten R, Donis RO (2007) FluGenome: a web tool for genotyping influenza A virus. Nucleic Acids Res 35: W275-279
        doi: 10.1093/nar/gkm365

    30. Lun AT, Wong JW, Downard KM (2012) FluShuffle and FluResort: new algorithms to identify reassorted strains of the influenza virus by mass spectrometry. BMC Bioinformatics 13: 208
        doi: 10.1186/1471-2105-13-208

    31. Martin D, Rybicki E (2000) RDP: detection of recombination amongst aligned sequences. Bioinformatics 16: 562-563
        doi: 10.1093/bioinformatics/16.6.562

    32. McGuire G, Wright F, Prentice MJ (1997) A graphical method for detecting recombination in phylogenetic data sets. Mol Biol Evol 14: 1125-1131
        doi: 10.1093/oxfordjournals.molbev.a025722

    33. Mena I, Nelson MI, Quezada-Monroy F, Dutta J, Cortes-Fernández R, Lara-Puente JH, Castro-Peralta F, Cunha LF, Trovão NS, Lozano-Dubernard B, Rambaut A, van Bakel H, García-Sastre A (2016) Origins of the 2009 H1N1 influenza pandemic in swine in Mexico. Elife 5: e16777
        doi: 10.7554/eLife.16777

    34. Nagarajan N, Kingsford C (2008) Uncovering genomic reassortments among influenza strains by enumerating maximal bicliques. Paper presented at the 2008 IEEE international conference on bioinformatics and biomedicine. https://doi.org/10.1109/BIBM.2008.78

    35. Nagarajan N, Kingsford C (2011) GiRaF: robust, computational identification of influenza reassortments via graph mining. Nucleic Acids Res 39: e34-e34
        doi: 10.1093/nar/gkq1232

    36. Nakajima K, Nobusawa E, Nagy A, Nakajima S (2005) Accumulation of amino acid substitutions promotes irreversible structural changes in the hemagglutinin of human influenza AH3 virus during evolution. J Virol 79: 6472-6477
        doi: 10.1128/JVI.79.10.6472-6477.2005

    37. Olsen CW, Karasin AI, Carman S, Li Y, Bastien N, Ojkic D, Alves D, Charbonneau G, Henning BM, Low DE, Burton L, Broukhanski G (2006) Triple reassortant H3N2 influenza A viruses, Canada, 2005. Emerg Infect Dis 12: 1132-1135
        doi: 10.3201/eid1207.060268

    38. Prosperi MC, Ciccozzi M, Fanti I, Saladini F, Pecorari M, Borghi V, Di Giambenedetto S, Bruzzone B, Capetti A, Vivarelli A, Rusconi S, Re MC, Gismondo MR, Sighinolfi L, Gray RR, Salemi M, Zazzi M, De Luca A (2011) A novel methodology for large-scale phylogeny partition. Nat Commun 2: 321
        doi: 10.1038/ncomms1325

    39. Rabadan R, Levine AJ, Krasnitz M (2008) Non-random reassortment in human influenza A viruses. Influenza Other Respir Viruses 2: 9-22
        doi: 10.1111/j.1750-2659.2007.00030.x

    40. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406-425
        doi: 10.1093/oxfordjournals.molbev.a040454

    41. Salzberg SL, Kingsford C, Cattoli G, Spiro DJ, Janies DA, Aly MM, Brown IH, Couacy-Hymann E, De Mia GM, Dung do H, Guercio A, Joannis T, Maken Ali AS, Osmani A, Padalino I, Saad MD, Savic V, Sengamalay NA, Yingst S, Zaborsky J, Zorman-Rojs O, Ghedin E, Capua I (2007) Genome analysis linking recent European and African influenza (H5N1) viruses. Emerg Infect Dis 13: 713-718
        doi: 10.3201/eid1305.070013

    42. Sawyer S (1989) Statistical tests for detecting gene conversion. Mol Biol Evol 6: 526-538

    43. Schäfer JR, Kawaoka Y, Bean WJ, Süss J, Senne D, Webster RG (1993) Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. Virology 194: 781-788
        doi: 10.1006/viro.1993.1319

    44. Smith GJ, Donis RO (2015) Nomenclature updates resulting from the evolution of avian influenza A(H5) virus clades 2.1.3.2a, 2.2.1, and 2.3.4 during 2013-2014. Influenza Other Respir Viruses 9: 271-276
        doi: 10.1111/irv.12324

    45. Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, Ma SK, Cheung CL, Raghwani J, Bhatt S, Peiris JS, Guan Y, Rambaut A (2009a) Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459: 1122-1125
        doi: 10.1038/nature08182

    46. Smith GJD, Bahl J, Vijaykrishna D, Zhang J, Poon LLM, Chen H, Webster RG, Peiris JSM, Guan Y (2009b) Dating the emergence of pandemic influenza viruses. Proc Natl Acad Sci 106: 11709-11712
        doi: 10.1073/pnas.0904991106

    47. Smith JM (1992) Analyzing the mosaic structure of genes. J Mol Evol 34: 126-129
        doi: 10.1007/BF00182389

    48. Sourdis J, Nei M (1988) Relative efficiencies of the maximum parsimony and distance-matrix methods in obtaining the correct phylogenetic tree. Mol Biol Evol 5: 298-311

    49. Su S, Fu X, Li G, Kerlin F, Veit M (2017) Novel Influenza D virus: epidemiology, pathology, evolution and biological characteristics. Virulence 8: 1580-1591
        doi: 10.1080/21505594.2017.1365216

    50. Suzuki Y (2010) A phylogenetic approach to detecting reassortments in viruses with segmented genomes. Gene 464: 11-16
        doi: 10.1016/j.gene.2010.05.002

    51. Svinti V, Cotton JA, McInerney JO (2013) New approaches for unravelling reassortment pathways. BMC Evol Biol 13: 1
        doi: 10.1186/1471-2148-13-1

    52. Takezaki N, Rzhetsky A, Nei M (1995) Phylogenetic test of the molecular clock and linearized trees. Mol Biol Evol 12: 823-833

    53. van Ravenzwaaij D, Cassey P, Brown SD (2018) A simple introduction to Markov Chain Monte-Carlo sampling. Psychon Bull Rev 25: 143-154
        doi: 10.3758/s13423-016-1015-8

    54. Vijaykrishna D, Poon LL, Zhu HC, Ma SK, Li OT, Cheung CL, Smith GJ, Peiris JS, Guan Y (2010) Reassortment of pandemic H1N1/2009 influenza A virus in swine. Science 328: 1529
        doi: 10.1126/science.1189132

    55. Villa M, Lassig M (2017) Fitness cost of reassortment in human influenza. PLoS Pathog 13: e1006685
        doi: 10.1371/journal.ppat.1006685

    56. Virk RK, Jayakumar J, Mendenhall IH, Moorthy M, Lam P, Linster M, Lim J, Lin C, Oon LLE, Lee HK, Koay ESC, Vijaykrishna D, Smith GJD, Su YCF (2020) Divergent evolutionary trajectories of influenza B viruses underlie their contemporaneous epidemic activity. Proc Natl Acad Sci USA 117: 619-628
        doi: 10.1073/pnas.1916585116

    57. Wan XF, Wu X, Lin G, Holton SB, Desmone RA, Shyu CR, Guan Y, Emch ME (2007a) Computational identification of reassortments in avian influenza viruses. Avian Dis 51: 434-439
        doi: 10.1637/7625-042706R1.1

    58. Wan XF, Chen G, Luo F, Emch M, Donis R (2007b) A quantitative genotype algorithm reflecting H5N1 Avian influenza niches. Bioinformatics 23: 2368-2375
        doi: 10.1093/bioinformatics/btm354

    59. Wan XF, Ozden M, Lin G (2008) Ubiquitous reassortments in influenza A viruses. J Bioinform Comput Biol 6: 981-999
        doi: 10.1142/S0219720008003813

    60. WHO/OIE/FAO H5N1 Evolution Working Group (2008) Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 14: e1

    61. WHO/OIE/FAO H5N1 Evolution Working Group (2009) Continuing progress towards a unified nomenclature for the highly pathogenic H5N1 avian influenza viruses: divergence of clade 2.2 viruses. Influenza Other Respir Viruses 3: 59-62
        doi: 10.1111/j.1750-2659.2009.00078.x

    62. WHO/OIE/FAO H5N1 Evolution Working Group (2012) Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature. Influenza Other Respir Viruses 6: 1-5
        doi: 10.1111/j.1750-2659.2011.00298.x

    63. Wu A, Su C, Wang D, Peng Y, Liu M, Hua S, Li T, Gao GF, Tang H, Chen J, Liu X, Shu Y, Peng D, Jiang T (2013) Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe 14: 446-452
        doi: 10.1016/j.chom.2013.09.001

    64. Xing G, Gu J, Yan L, Lei J, Lai A, Su S, Zhou J (2016) Human infections by avian influenza virus H5N6: Increasing risk by dynamic reassortment? Infect Genet Evol 42: 46-48
        doi: 10.1016/j.meegid.2016.04.009

    65. Yin R, Zhou X, Rashid S, Kwoh CK (2020) HopPER: an adaptive model for probability estimation of influenza reassortment through host prediction. BMC Med Genomics 13: 9
        doi: 10.1186/s12920-019-0656-7

    66. Yurovsky A, Moret BME (2011) FluReF, an automated flu virus reassortment finder based on phylogenetic trees. BMC Genomics 12: S3
        doi: 10.1186/1471-2164-12-S2-S3

  • 加载中

Figures(2) / Tables(1)

Article Metrics

Article views(2210) PDF downloads(5) Cited by()

Related
Proportional views
    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Progress and Challenge in Computational Identification of Influenza Virus Reassortment

      Corresponding author: Taijiao Jiang, taijiao@ibms.pumc.edu.cn
    • 1. Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
    • 2. College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, China
    • 3. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China
    • 4. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China

    Abstract: 

    Genomic reassortment is an important evolutionary mechanism for influenza viruses. In this process, the novel viruses acquire new characteristics by the exchange of the intact gene segments among multiple influenza virus genomes, which may cause flu endemics and epidemics within or even across hosts. Due to the safety and ethical limitations of the experimental studies on influenza virus reassortment, numerous computational researches on the influenza virus reassortment have been done with the explosion of the influenza virus genomic data. A great amount of computational methods and bioinformatics databases were developed to facilitate the identification of influenza virus reassortments. In this review, we summarized the progress and challenge of the bioinformatics research on influenza virus reassortment, which can guide the researchers to investigate the influenza virus reassortment events reasonably and provide valuable insight to develop the related computational identification tools.