HIV classification using the coalescent theory

Abstract

Motivation: Existing coalescent models and phylogenetic tools based on them are not designed for studying the genealogy of sequences like those of HIV since in HIV recombinants with multi-ple cross-over points between the parental strains frequently arise. Hence, ambiguous cases in the classification of HIV sequences into subtypes and Circulating Recombinant Forms (CRFs) have been treated with ad hoc methods in lack of tools based on a com-prehensive coalescent model accounting for complex recombination patterns. Results: We developed the program ARGUS that scores classi-fications of sequences into subtypes and recombinant forms. It reconstructs Ancestral Recombination Graphs (ARGs) that reflect the genealogy of the input sequences given a classification hypothesis. An ARG with maximal probability is approximated using a Markov Chain Monte Carlo approach. ARGUS was able to distinguish the correct classification with a low error rate from plausible alterna-tive classifications in simulation studies with realistic parameters. We applied our algorithm to decide between two recently debated alter-natives in the classification of CRF02 of HIV-1 and find that CRF02 is indeed a recombinant of subtypes A and G. Availability: ARGUS is implemented in C++ and the source code is available a