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Quantification of epistasis for abundance and IC50 in DHFR mutants
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Data_S3_Biophysical parameters.xlsx
GGG Whole Raw Set Clean.xlsx

Epistasis for antibiotic resistance

This code runs the analyses described in Guerrero et al. (2019) "Proteostasis environment shapes higher-order epistasis operating on antibiotic resistance". The goal is to infer interactions acting on three phenotypes measured for nine strains of E. coli (including transgenic strains and evolved mutants).

The analyses use functions from the and tidyverse packages. The plots call functions from treemapify and cowplot.

Load data

The script ms1_load_data.R reads two data files ('GGG Whole Raw Set Clean.xlsx' and 'zero_growth_rate_reps.csv') carries out basic transformations. The allphenos data frame contains all the data for downstream analysis, coded in the following columns: 'context'-- one of three proteostasis environments (WT, GroEL, lon). 'species'-- one of three DHFR backbones, from E.coli, C. muridarum, or L. grayi. 'binary'-- the haplotype at the three sites of interest (coded from 000 to 111) 'pheno'-- the type of phenotype (IC50, abundance, or growth) 'W'-- the value of the phenotype 'logW'--the log10 of variable 'W'.

Linear models

The script ms1_linear_models.R "sources" the previous step (loads data) and carries out the bulk of the regularized regressions. The key functions are: run_long_lm -- carry out Elastic Net on the model ~ species * context * P21L * A26T * L28R. It assumes a gaussian error distribution and intercept of zero. It does n-fold cross-validation (n = number of observations). The dependent variable can be set through parameter yname. If yname=="normy", then it assumes the dependent variable is already normalized. Otherwise it normalizes it (recommended for regularized regressions). The function returns the coefficients at lambda_min + 1 std.error (calculated through the cross-validation).

one_cs_lm -- carries out Elastic Net on the model ~ P21L * A26T * L28R (meant to be fit to subsets of the data, by context-species). It always normalizes the dependent variable first (which can be set through parameter yvar). It also does n-fold cross-validation and returns coefficients at lambda_min + 1 std.error.

Plots and supplement

The scripts ms1_plots.R and ms1_supplemental.R source the linear models script and produce unpolished PDF versions of all the plots in the manuscript.

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