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

Journal: Genome biology
Published Date:

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.

Authors

  • Ammar Tareen
    Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
  • Mahdi Kooshkbaghi
    Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
  • Anna Posfai
    Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
  • William T Ireland
    Department of Physics, California Institute of Technology, Pasadena, 91125, CA, USA.
  • David M McCandlish
    Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
  • Justin B Kinney
    Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA. jkinney@cshl.edu.