Virus variation resources at the National Center for Biotechnology Information: dengue virus

Abstract

Background: There is an increasing number of complete and incomplete virus genome sequences available in public databases. This large body of sequence data harbors information about epidemiology, phylogeny, and virulence. Several specialized databases, such as the NCBI Influenza Virus Resource or the Los Alamos HIV database, offer sophisticated query interfaces along with integrated exploratory data analysis tools for individual virus species to facilitate extracting this information. Thus far, there has not been a comprehensive database for dengue virus, a significant public health threat.

Results: We have created an integrated web resource for dengue virus. The technology developed for the NCBI Influenza Virus Resource has been extended to process non-segmented dengue virus genomes. In order to allow efficient processing of the dengue genome, which is large in comparison with individual influenza segments, we developed an offline pre-alignment procedure which generates a multiple sequence alignment of all dengue sequences. The pre-calculated alignment is then used to rapidly create alignments of sequence subsets in response to user queries. This improvement in technology will also facilitate the incorporation of additional virus species in the future. The set of virus-specific databases at NCBI, which will be referred to as Virus Variation Resources (VVR), allow users to build complex queries against virus-specific databases and then apply exploratory data analysis tools to the results. The metadata is automatically collected where possible, and extended with data extracted from the literature.

Conclusion: The NCBI Dengue Virus Resource integrates dengue sequence information with relevant metadata (sample collection time and location, disease severity, serotype, sequenced genome region) and facilitates retrieval and preliminary analysis of dengue sequences using integrated web analysis and visualization tools.

Figure 1

Dengue cases reported worldwide from 1955 to 2004. The number of dengue cases as reported in the WHO DengueNet database [16] from 1955 to 2004.

Figure 2

Data overview. Frequency of (A) collection years (N = 4543), (B) genome regions (N = 6235), (C) sequence lengths (N = 6235), and (D) collection countries (N = 5635) for dengue records in VVR.

Figure 3

Interface. (A) Dengue virus query form; (B) Results page for query; (C) Multiple alignment view for results; (D) Neighbor joining tree based on nucleotide distances of codon-aligned open reading frames. Dengue serotype 1 sequences are tagged with green markers. Large branches are aggregated.

Figure 4

Case study. A clustering tree built using the the complete linkage hierarchical clustering algorithm and the F84 distances for 114 coding sequences of DENV-3 virus envelope proteins of isolates collected in Thailand and having collection year on record. Sequences obtained prior to 1992 were selected using the tree viewing option menu and highlighted in red. Most of pre-1992 DEV-3 sequences in Thailand fall in a distinct cluster.