Tools for investigating mechanisms of antigenic variation: new extensions to varDB.

Abstract

The varDB project (http://www.vardb.org) aims to create and maintain a curated database of antigenic variation sequences as well as a platform for online sequence analysis. Along with the evolution of drug resistance, antigenic variation presents a moving target for public health endeavors and greatly complicates vaccination and eradication efforts. However, careful analysis of a large number of variant forms may reveal structural and functional constraints that can be exploited to identify stable and cross-reactive targets. VarDB attempts to facilitate this effort by providing streamlined interfaces to standard tools to help identify and prepare sequences for various forms of analysis. We have newly implemented such tools for codon usage, selection, recombination, secondary and tertiary structure, and sequence diversity analysis. Just as the adaptive immune system encodes a mechanism for dynamically generating diverse receptors instead of encoding a receptor for every possible epitope, many pathogens take advantage of heritable diversity generating mechanisms to produce progeny able to evade immune recognition. Instead of merely cataloging the observed variation, a major goal of varDB is to characterize and predict the potential range of antigenic variation within a pathogen by investigating the mechanisms by which it attempts to expand its implicit genome. We believe that the new sequence analysis tools will improve the usefulness and range of varDB.