Phylogenetic dependency networks: inferring patterns of CTL escape and codon covariation in HIV-1 Gag.

ABSTRACT: HIV avoids elimination by cytotoxic T-lymphocytes (CTLs) through the evolution of escape mutations. Although there is mounting evidence that these escape pathways are broadly consistent among individuals with similar human leukocyte antigen (HLA) class I alleles, previous population-based studies have been limited by the inability to simultaneously account for HIV codon covariation, linkage disequilibrium among HLA alleles, and the confounding effects of HIV phylogeny when attempting to identify HLA-associated viral evolution. We have developed a statistical model of evolution, called a phylogenetic dependency network, that accounts for these three sources of confounding and identifies the primary sources of selection pressure acting on each HIV codon. Using synthetic data, we demonstrate

SUBMITTER: Carlson JM 

PROVIDER: S-EPMC2579584 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature