AMRgen is an open-source R package designed to bridge the gap between genotypic and phenotypic antimicrobial resistance (AMR) data. Developed as an extension to the AMR R package, it provides tools to interpret AMR genes, integrate these findings with antimicrobial susceptibility test (AST) data, and calculate genotype-phenotype associations.

This package is developed in collaboration with the ESGEM-AMR Working Group and is tailored for researchers and healthcare professionals tackling AMR globally.

The AMRgen website has full function documentation and various vignettes working through analysing geno/pheno data using key functions.

• Import Genotype and Phenotype Data: Import from common formats (NCBI or EBI antibiogram format, VITEK, Sensititre, MicroScan, Phoenix, WHONet for phenotypes; AMRFinderPlus, ABRicate, Kleborate, RGI and AMRrules for genotypes.
• Genotype-Phenotype Integration: Links AMR gene presence with phenotypic resistance profiles, enabling deeper insights into resistance mechanisms.
• Automated EUCAST MIC Distribution Integration: Fetch MIC distribution data directly from EUCAST for seamless comparison with local susceptibility data.
• Visualisation: Generate powerful UpSet plots to identify intersections of AMR gene presence and phenotypic resistance, highlighting multidrug resistance patterns.
• Modular and Extensible: Leverages the robust foundation of the AMR package, including antibiotic selectors and clinical breakpoint interpretations.
• NCBI- and EBI-Compliant Export: Export phenotype data to NCBI- and EBI-compliant antibiogram format.

To install and explore the package, follow the instructions below:

It is best to restart R before running the installation to prevent issues.

Install the latest version of this package with:

install.packages("remotes") # if you haven't already
remotes::install_github("AMRverse/AMRgen")

All required packages, including the AMR package if you don't have it already, will be installed automatically.

If you have issues, we recommend you install the latest version of the AMR package directly, then try again to install AMRgen:

install.packages("remotes") # if you haven't already
remotes::install_github("msberends/AMR")
remotes::install_github("AMRverse/AMRgen")

If you still have trouble with installation please post an issue here! The package is new and we want to make it as accessible as possible for new users.

library(AMRgen)

Below is a quick example demonstrating the major functions with AMRgen and how they can be used to compare ciprofloxacin resistance phenotypes with quinolone genotype markers, in E. coli.

# Example public E. coli AST data from NCBI
#  (already imported via import_ncbi_ast() and re-interpreted with as.sir())
ecoli_ast

# Import matching E. coli AMRFinderPlus data from AllTheBacteria
ecoli_geno <- import_amrfp(ecoli_geno_raw, "Name")

# Calculate solo positive predictive value for ciprofloxacin resistance, for individual markers found solo
#  (for all quinolone-associated genotype markers)
soloPPV_cipro <- solo_ppv_analysis(ecoli_geno, ecoli_ast, antibiotic="Ciprofloxacin", drug_class_list=c("Quinolones"), sir_col="pheno_clsi")

# Do upset plot of ciprofloxacin MIC vs quinolone genotype marker combinations
#  (for combinations observed at least 5 times)
cip_upset <- amr_upset(binary_matrix=soloPPV_cipro$amr_binary, min_set_size=5, assay="mic")

# Calculate positive predictive value for individual markers and combinations
cip_ppv <- ppv(binary_matrix=soloPPV_cipro$amr_binary, min_set_size=5)

# Do logistic regression of ciprofloxacin resistance as a function of presence/absence of quinolone-associated markers
#  (for markers observed at least 10 times)
models <- amr_logistic(binary_matrix=soloPPV_cipro$amr_binary, maf=10)

# Caclulate concordance of genotype and phenotype markers
eco_cip_matrix <- get_binary_matrix(ecoli_geno, ecoli_ast, antibiotic = "Ciprofloxacin", drug_class_list = "Quinolones", sir_col = "pheno_provided", keep_assay_values = TRUE, keep_assay_values_from = "mic")

concordance_cip <- concordance(eco_cip_matrix)

To learn how to download data from the public archives NCBI or EBI

You can see all the various phenotypic import functions for the following formats by running:

?import_ast

Currently, AMRgen supports the following phenotype formats:

• EBI
• NCBI
• VITEK
• MicroScan
• SensiTitre
• WHOnet

Phenotype data can also be exported in NCBI or EBI formats, for upload to the public archives:

?export_ncbi_ast
?export_ebi_ast

For a complete example of how to analyse your genotypic and phenotypic data together, see Analysing Geno-Pheno Data.

Example analysis of a small Salmonella enterica dataset for ciprofloxacin resistance

Example analysis of clindamycin resistance in Staphylococcus aureus

Example analysis using large-scale surviellance genotype and phenotype data in Neiserria gonohorroeae

How to assess concordance of predicted phenotypes with observed phenotypes

For more see the various vignettes.

# Get MIC reference distribution for ciprofloxacin in E. coli
ecoli_cip_mic_data <- get_eucast_mic_distribution("cipro", "E. coli")

# Plot the reference distribution 
mics <- rep(ecoli_cip_mic_data$mic, ecoli_cip_mic_data$count)
ggplot2::autoplot(mics, ab = "cipro", mo = "E. coli", title = "E. coli cipro reference distribution")

# Compare reference distribution to example E. coli data
ecoli_cip <- ecoli_ast$mic[ecoli_ast$drug_agent=="CIP"]
comparison <- compare_mic_with_eucast(ecoli_cip, ab = "cipro", mo = "E. coli")
comparison
ggplot2::autoplot(comparison)

Contributions are welcome! If you encounter issues or wish to suggest new features, please open an issue or submit a pull request.

This package is distributed under the GNU GPL-3.0 Licence. See LICENSE for details.