title: Novel bioinformatics strategies for prediction of directional sequence changes in influenza virus genomes and for surveillance of potentially hazardous strains.
abstract: BACKGROUND
  With the remarkable increase of microbial and viral sequence data obtained from high-throughput DNA sequencers, novel tools are needed for comprehensive analysis of the big sequence data. We have developed "Batch-Learning Self-Organizing Map (BLSOM)" which can characterize very many, even millions of, genomic sequences on one plane. Influenza virus is one of zoonotic viruses and shows clear host tropism. Important issues for bioinformatics studies of influenza viruses are prediction of genomic sequence changes in the near future and surveillance of potentially hazardous strains.
  
  
  METHODS
  To characterize sequence changes in influenza virus genomes after invasion into humans from other animal hosts, we applied BLSOMs to analyses of mono-, di-, tri-, and tetranucleotide compositions in all genome sequences of influenza A and B viruses and found clear host-dependent clustering (self-organization) of the sequences.
  
  
  RESULTS
  Viruses isolated from humans and birds differed in mononucleotide composition from each other. In addition, host-dependent oligonucleotide compositions that could not be explained with the host-dependent mononucleotide composition were revealed by oligonucleotide BLSOMs. Retrospective time-dependent directional changes of mono- and oligonucleotide compositions, which were visualized for human strains on BLSOMs, could provide predictive information about sequence changes in newly invaded viruses from other animal hosts (e.g. the swine-derived pandemic H1N1/09).
  
  
  CONCLUSIONS
  Basing on the host-dependent oligonucleotide composition, we proposed a strategy for prediction of directional changes of virus sequences and for surveillance of potentially hazardous strains when introduced into human populations from non-human sources. Millions of genomic sequences from infectious microbes and viruses have become available because of their medical and social importance, and BLSOM can characterize the big data and support efficient knowledge discovery.
authors: Department of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama-shiShiga-ken, 526-0829, Japan.
authors: Yuki
authors: Y
authors: Iwasaki
authors: Takashi
authors: T
authors: Abe
authors: Yoshiko
authors: Y
authors: Wada
authors: Kennosuke
authors: K
authors: Wada
authors: Toshimichi
authors: T
authors: Ikemura
mesh_terms: D030541:Databases, Genetic; D016679:Genome, Viral; D023281:Genomics / Q000379:methods*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D009980:Influenza A virus / Q000235:genetics*; D009981:Influenza B virus / Q000235:genetics*; D007251:Influenza, Human / Q000821:virology*; D008957:Models, Genetic; D012367:RNA, Viral; D012189:Retrospective Studies; D017423:Sequence Analysis, RNA; D056189:Viral Tropism
chemical_list: D012367:RNA, Viral
references: Mol Biol Evol. 1985 Jan;2(1):13-34
references: 3916708
references: J Virol. 2006 Dec;80(23):11887-91
references: 16987977
references: Virology. 2001 Jan 20;279(2):375-84
references: 11162793
references: Mol Biol Evol. 1999 Oct;16(10):1315-28
references: 10563013
references: Science. 1999 Dec 3;286(5446):1921-5
references: 10583948
references: Science. 2009 Jul 10;325(5937):197-201
references: 19465683
references: Genome Res. 2001 Apr;11(4):540-6
references: 11282969
references: DNA Res. 2011 Apr;18(2):125-36
references: 21444341
references: Mol Biol Evol. 2006 Oct;23(10):1902-11
references: 16818477
references: Avian Dis. 2010 Dec;54(4):1275-85
references: 21313850
references: Mol Biol Evol. 2004 Dec;21(12):2352-9
references: 15356273
references: Annu Rev Genet. 1998;32:185-225
references: 9928479
references: Annu Rev Microbiol. 1997;51:151-78
references: 9343347
references: DNA Res. 2005;12(5):281-90
references: 16769690
references: J Gen Virol. 2007 Oct;88(Pt 10):2627-2635
references: 17872512
references: PLoS Pathog. 2008 Jun 06;4(6):e1000079
references: 18535658
references: Nature. 2009 Jun 25;459(7250):1122-5
references: 19516283
references: J Virol. 2008 Jan;82(2):596-601
references: 17942553
references: Nat Rev Genet. 2007 Mar;8(3):196-205
references: 17262054
references: Nat Rev Genet. 2005 Mar;6(3):206-20
references: 15703763
references: DNA Res. 2009 Oct;16(5):287-97
references: 19801558
references: Gene. 2001 Oct 3;276(1-2):89-99
references: 11591475
references: Genome Res. 2003 Apr;13(4):693-702
references: 12671005
references: MMWR Morb Mortal Wkly Rep. 2009 Apr 24;58(15):400-2
references: 19390508