LASSIE is an acronym for "longitudinal antigenic sites and sequences from intrahost evolution" or "longitudinal antigenic swarm selection from intrahost evolution". It starts with a sequence alignment sampled serially from an infected host, which characterizes a pathogen population evolving under immune selection. The population is related by a single common "transmitted- founder" (TF) ancestor. The first phase of analysis computes TF loss per aligned site for each time-point sampled, to select sites of interest where TF loss exceeds a threshold. Sites that lose the ancestral TF amino acids are likely under positive selection and merit further investigation. The second phase selects a set of sequences with mutations among selected sites. A swarm of sequences represents diversity in the population sampled and can subsequently be used to study developing immune responses. Example data are included to identify sites on the HIV-1 envelope glycoprotein, to characterize affinity maturation which leads to a broadly neutralizing antibody response.
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