MAVE-NN: learning genotype-phenotype maps from multiplex assays of variant effect

Genome Biol. 2022 Apr 15;23(1):98. doi: 10.1186/s13059-022-02661-7.

Abstract

Multiplex assays of variant effect (MAVEs) are a family of methods that includes deep mutational scanning experiments on proteins and massively parallel reporter assays on gene regulatory sequences. Despite their increasing popularity, a general strategy for inferring quantitative models of genotype-phenotype maps from MAVE data is lacking. Here we introduce MAVE-NN, a neural-network-based Python package that implements a broadly applicable information-theoretic framework for learning genotype-phenotype maps-including biophysically interpretable models-from MAVE datasets. We demonstrate MAVE-NN in multiple biological contexts, and highlight the ability of our approach to deconvolve mutational effects from otherwise confounding experimental nonlinearities and noise.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay*
  • Genotype
  • Mutation
  • Neural Networks, Computer*
  • Phenotype