Tools for Investigating Mechanisms of Antigenic Variation: New Extensions to varDB


C.Nelson Hayes[1] (nelson@kuicr.kyoto-u.ac.jp)
Diego Diez[1] (diez@kuicr.kyoto-u.ac.jp)
Nicolas Joannin[2][3] (nicolas.joannin@ki.se)
Minoru Kanehisa[1] (kanehisa@kuicr.kyoto-u.ac.jp)
Mats Wahlgren[2][3] (mats.wahlgren@ki.se)
Craig E. Wheelock[1][4]* (craig.wheelock@ki.se)
Susumu Goto[1]* (goto@kuicr.kyoto-u.ac.jp)

[1] Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Ky-oto 611-0011, Japan
[2] Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Box 280, SE-17177 Stockholm, Sweden
[3] Swedish Institute for Infectious Disease Control (Smittskyddsinstitutet), SE-17182 Stockholm, Sweden
[4] Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden
(*)To whom correspondence should be addressed

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 anal- ysis. Along with the evolution of drug resistance, antigenic variation presents a moving target for public health endeavors and greatly complicates vaccination and eradication eorts. 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 tar- gets. VarDB attempts to facilitate this eort by providing streamlined interfaces to stan- dard 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.

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Japanese Society for Bioinformatics