Generative AAV capsid diversification by latent interpolation thumbnail
Generative AAV capsid diversification by latent interpolation
www.biorxiv.org
show that a low-complexity Variational Auto-encoder (VAE) can interpolate in sequence space to produce diverse and novel capsids capable of packaging their own genomes select a 28 amino acid window near the heparin binding site experimental data we use consists of 36,562 variants of AAV2 (substituti
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  • show that a low-complexity Variational Auto-encoder (VAE) can interpolate in sequence space to produce diverse and novel capsids capable of packaging their own genomes
  • select a 28 amino acid window near the heparin binding site
  • experimental data we use consists of 36,562 variants of AAV2 (substitution only) mutants of which 22,704 we classified as viable
  • (i) Evolutionary data (MSA) alone (n=564) (ii) Evolutionary data supplemented 667 randomly generated viable variants (MSAr) from a deep mutational exploration (n=1,231) and finally (iii) Evolutionary data augmented by 22,704 viable (MSA+) mutants 1-21 mutations from wildtype generated at random or an additive model (n=23,268)
  • viral variants likely capable of generating functional assemblies

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