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SCIENCE AT THE EDGE SEMINAR
QB/GEDD
Friday, September 21 at 11:30am
Room 1400 Biomedical and Physical Sciences Bldg.
Refreshments at 11:15
Richard Scheuermann
J. Craig Venter Institute
San Diego, California
Sequence Feature Variant Type and Evolutionary Trajectory Analysis
using the Influenza Research Database
The recent experience with the emergence of the 2009 Pandemic H1N1 virus has highlighted the value of free and open access to genome sequence data integrated with information about
viral characteristics related to antiviral drug resistance and virulence for influenza viruses. The Influenza Research Database (IRD) (www.fludb.org) is a free, publicly accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases
(NIAID) through the Bioinformatics Resource Centers (BRC) program that serves as a comprehensive integrated database and analysis resource for influenza sequence, surveillance and research data. The IRD provides researchers access to user-friendly interfaces
for data retrieval, analysis, and visualization tools. IRD integrates genomic, proteomic, immune epitopes, and surveillance data with other information useful in understanding virulence and host-pathogen interactions.
IRD also contains novel data related to influenza virus not found in other database resource. Curators at IRD have assembled a set of >4500 sequence features
(SF) in the 11 influenza proteins. A sequence feature can be a specific functional region (e.g. enzyme active site), a structural feature (e.g. a particular alpha helix), an immune epitope, or any other region of special interest. IRD then determine the
number of unique amino acid sequences for each SF from the entire database of sequence record as the set of variant types (VT) for each SF. An analysis of associations between SFVT’s and virus host range has revealed that genetic determinants in the influenza
NS1 protein restrict the host range of influenza viruses.
In April and May 2009, the first cases of a new influenza-like illness were reported in California, Texas and Mexico. A novel influenza virus strain, Pandemic H1N1 2009 (aka “swine flu”), had emerged as the
first official pandemic strain of the 21st century. Early analysis pointed to the swine origin of the virus overall, but there was debate as to the origin of each of the eight genomic segments since segments from two or more influenza strains are known to
re-assort. Traditionally, investigators address this question by performing a BLAST analysis to identify closely related sequences as candidate ancestral genomes. However, in the process of evaluating BLAST analysis results we identified interesting patterns
when we plotted nucleotide differences versus isolation year differences between the pandemic strain and the top 1000 BLAST hits. These plots showed three distinct clusters for segment 5 encoding the nucleoprotein NP. Similar patterns were observed for other
genomic segments. Manual segregation of these sequence records and subsequent phylogenetic and sequence alignments analysis showed that sequences in Cluster 1 exhibit a gentle trajectory of sequence similarity consistent with the gradual accumulation of mutations
over time, whereas sequences in Cluster 2 show a more haphazard pattern of sequence similarity. These observations and others suggested that sequences in Cluster 1 represent the true evolutionary trajectory of the pandemic strain. We are now developing new
computational approaches to illuminate the true evolutionary trajectory of virus sequences based on these observations. These results suggest that this novel evolutionary trajectory (ET) analysis can more effectively pinpoints the host and geographiclineages
of viral genome segment, in comparison with BLAST-based phylogenetic analysis alone. Supported by NIH N01AI40041.
Helen Geiger, Administrative Assistant
Quantitative Biology Graduate Program and
Gene Expression in Development and Disease
Biochemistry
603 Wilson Road, Room 212
East Lansing, MI 48824
Email: [log in to unmask]
Phone: 517-432-9895
QB Website: http://www.qbi.msu.edu/
GEDD Website: http://www.gedd.msu.edu/