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

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作者
Ammar Tareen
Mahdi Kooshkbaghi
Anna Posfai
William T. Ireland
David M. McCandlish
Justin B. Kinney
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[1] Simons Center for Quantitative Biology,Department of Physics
[2] Cold Spring Harbor Laboratory,Present Address: Department of Applied Physics
[3] Present Address: Regeneron Pharmaceuticals,undefined
[4] Inc.,undefined
[5] California Institute of Technology,undefined
[6] Harvard University,undefined
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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.
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