A Novel Bioinformatics Strategy to Predict Directional Changes of Influenza A Virus Genome Sequences

Influenza A viruses cause a significant threat to public health as highlighted by the recent introduction of the swine-derived H1N1 virus (pandemic H1N1/09) into human populations. Pandemics were primarily initiated by introduction from animal sources and successive adaptation among humans through human-to-human transmission. We established a sequence alignment-free clustering method "BLSOM", which can analyze and compare all influenza A virus genome sequences on one map. Separation according to host animal, subtype and epidemic year could be efficiently visualized. Notably, H1N1/09 strains have oligonucleotide and codon compositions clearly distinct from those of seasonal human flu strains. This enabled us to make inferences about directional changes of H1N1/09 sequences in the near future and to list codons and oligonucleotides with the potential of reduction in H1N1/09 sequences. The strong visualization power of BLSOM also provides surveillance strategies for efficiently detecting potential precursors to pandemic viruses.

[1]  Hideaki Sugawara,et al.  Novel phylogenetic studies of genomic sequence fragments derived from uncultured microbe mixtures in environmental and clinical samples. , 2005, DNA research : an international journal for rapid publication of reports on genes and genomes.

[2]  K. Moelling,et al.  Dicer is involved in protection against influenza A virus infection. , 2007, The Journal of general virology.

[3]  S. Kanaya,et al.  Analysis of codon usage diversity of bacterial genes with a self-organizing map (SOM): characterization of horizontally transferred genes with emphasis on the E. coli O157 genome. , 2001, Gene.

[4]  T. Ikemura.  Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. , 1981, Journal of molecular biology.

[5]  N. Sueoka.  Intrastrand parity rules of DNA base composition and usage biases of synonymous codons , 1995, Journal of Molecular Evolution.

[6]  T. Kohonen.  Self-organized formation of topographically correct feature maps , 1982 .

[7]  Ron A M Fouchier,et al.  Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans , 2009, Science.

[8]  Gavin J. D. Smith,et al.  Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic , 2009, Nature.

[9]  A. García-Sastre,et al.  Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative-strand RNA viruses. , 2001, Virology.

[10]  Shigehiko Kanaya,et al.  Informatics for unveiling hidden genome signatures. , 2003, Genome research.

[11]  Erkki Oja,et al.  Engineering applications of the self-organizing map , 1996, Proc. IEEE.

[12]  Hideaki Sugawara,et al.  Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes , 2006, Nucleic Acids Res..

[13]  Teuvo Kohonen,et al.  Self-organized formation of topologically correct feature maps , 2004, Biological Cybernetics.

[14]  P. Sharp,et al.  Codon usage and genome evolution. , 1994, Current opinion in genetics & development.

[15]  T. Ikemura.  Codon usage and tRNA content in unicellular and multicellular organisms. , 1985, Molecular biology and evolution.

[16]  T. Tatusova,et al.  The Influenza Virus Resource at the National Center for Biotechnology Information , 2007, Journal of Virology.

[17]  E. Holmes,et al.  The evolution of epidemic influenza , 2007, Nature Reviews Genetics.

[18]  E. Domingo,et al.  RNA virus mutations and fitness for survival. , 1997, Annual review of microbiology.