wavess 1.2: Presenting an HLA-aware within-host virus sequence simulation framework

Abstract

Motivation: Understanding how virus sequences are shaped by selection can inform vaccine design and transmission inference. Modeling within-host evolution to interrogate these questions requires a detailed mechanistic framework that accurately captures sequence diversification. The CD8+ cytotoxic T-lymphocyte (CTL) response plays an important role in immune-mediated selection and can leave strong signatures in virus sequences; however, existing sequence-based within-host virus modeling frameworks do not explicitly include an HLA-aware CTL response.

Results: We extended our previously published within-host sequence evolution simulator, wavess, to include an explicit CTL response, and share a method for identifying HLA-specific CTL epitopes given a founder virus sequence. We also updated the model to permit a variable recombination rate, which allows for modeling recombination hotspots, non-adjacent genes, and segmented genomes. These extensions to wavess allow for more accurate simulation of viruses and virus genes, particularly in regions of the genome where the immune response is dominated by CTLs (rather than antibodies). It also provides the foundation for investigations of how these newly-added biological mechanisms influence within-host evolution.

Availability and implementation: The core of wavess is written in Python 3, with helper functions written in R. It is available at https://github.com/MolEvolEpid/wavess.