ARMADiLLO: a web server for analyzing antibody mutation probabilities.

Abstract

Antibodies are generated by B cells that evolve receptor specificity to pathogens through rounds of mutation and selection in a process called affinity maturation. Somatic hypermutation is mediated by an enzyme with DNA sequence context-dependent targeting and substitution resulting in variable probabilities of amino acid substitutions during affinity maturation. We have previously developed a program called Antigen Receptor Mutation Analyzer for the Detection of Low Likelihood Occurrences (ARMADiLLO) that performs simulations of the somatic hypermutation process to estimate the probabilities of observed antibody mutations. Here we describe the ARMADiLLO web server (https://armadillo.dhvi.duke.edu), an easy-to-use web interface that analyzes input antibody sequences and displays the probability estimates for all possible amino acid changes over the full length of an antibody sequence. The probability of antibody mutations can be used by immunologists studying B cell ontogenies and by vaccine designers that are pursuing strategies to elicit broadly neutralizing antibodies which are enriched with developmentally rate-limiting improbable mutations. The ARMADiLLO web server also contains precomputed results reporting the probability of amino acid substitutions in all human V gene segments and in a collection of HIV broadly neutralizing antibodies.