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Perform Solo PPV Analysis for AMR Markers

Source: R/solo_ppv.R
solo_ppv_analysis.Rd

This function performs a Positive Predictive Value (PPV) analysis for AMR markers associated with a given antibiotic and drug class. It calculates the PPV for solo markers and visualizes the results using various plots.

Usage

solo_ppv_analysis(
  geno_table,
  pheno_table,
  antibiotic,
  drug_class_list,
  geno_sample_col = NULL,
  pheno_sample_col = NULL,
  sir_col = NULL,
  ecoff_col = "ecoff",
  icat = FALSE,
  marker_col = "marker",
  keep_assay_values = TRUE,
  min = 1,
  axis_label_size = 9,
  pd = position_dodge(width = 0.8),
  plot_cols = c(R = "maroon", I = "skyblue", NWT = "navy"),
  excludeRanges = c("NWT")
)

Arguments

geno_table

A data frame containing genotype data, including at least one column labeled drug_class for drug class information and one column for sample identifiers (specified via geno_sample_col otherwise it is assumed the first column contains identifiers).

pheno_table

A data frame containing phenotype data, which must include a column drug_agent (with the antibiotic information) and a column with the resistance interpretation (S/I/R, colname specified via sir_col).

antibiotic

A character string specifying the antibiotic of interest to filter phenotype data. The value must match one of the entries in the drug_agent column of pheno_table.

drug_class_list

A character vector of drug classes to filter genotype data for markers related to the specified antibiotic. Markers in geno_table will be filtered based on whether their drug_class matches any value in this list.

geno_sample_col

A character string (optional) specifying the column name in geno_table containing sample identifiers. Defaults to NULL, in which case it is assumed the first column contains identifiers.

pheno_sample_col

A character string (optional) specifying the column name in pheno_table containing sample identifiers. Defaults to NULL, in which case it is assumed the first column contains identifiers.

sir_col

A character string specifying the column name in pheno_table that contains the resistance interpretation (SIR) data. The values should be interpretable as "R" (resistant), "I" (intermediate), or "S" (susceptible).

ecoff_col

A character string (optional) specifying the column name in pheno_table that contains resistance interpretations (SIR) made against the ECOFF rather than a clinical breakpoint. The values should be interpretable as "R" (resistant), "I" (intermediate), or "S" (susceptible).

icat

A logical indicating whether to calculate PPV for "I" (if such a category exists in the phenotype column) (default FALSE).

marker_col

A character string specifying the column name in geno_table containing the marker identifiers. Defaults to "marker".

keep_assay_values

A logical indicating whether to include columns with the raw phenotype assay data in the binary matrix. Assumes there are columns labelled "mic" and/or "disk"; these will be added to the output table if present. Defaults to TRUE.

min

Minimum number of genomes with the solo marker, to include the marker in the plot (default 1).

axis_label_size

Font size for axis labels in the PPV plot (default 9).

pd

Position dodge, i.e. spacing for the R/NWT values to be positioned above/below the line in the PPV plot. Default 'position_dodge(width = 0.8)'.

plot_cols

A named vector of colors for the plot. The names should be the phenotype categories (e.g., "R", "I", "S", "NWT"), and the values should be valid color names or hexadecimal color codes. Default colors are provided for resistant ("R"), intermediate ("I"), susceptible ("S"), and non-wild-type ("NWT").

excludeRanges

Vector of phenotype categories (comprised of "R", "I", "NWT") for which we should ignore MIC values expressed as ranges when calculating PPVs. Default c("NWT"), as calling against ECOFF with the AMR package currently does not interpret ranges correctly. To include MICs expressed as ranges set this to NULL.

Value

A list containing the following elements:

  • solo_stats: A dataframe summarizing the PPV for resistance (R vs S/I) and NWT (R/I vs S), including the number of positive hits, sample size, PPV, and 95% confidence intervals for each marker.

  • combined_plot: A combined ggplot object showing the PPV plot for the solo markers, and a bar plot for the phenotype distribution.

  • solo_binary: A dataframe with binary values indicating the presence or absence of the solo markers.

  • amr_binary: A dataframe with binary values for the AMR markers, based on the input genotype and phenotype data.

Details

The function analyzes the predictive power of individual AMR markers that belong to a specified drug class and are uniquely associated with one class. The phenotype data are matched with genotype presence/absence and then stratified to compute PPV for resistance and non-wild-type interpretations. It also generates plots to aid in interpretation.

Examples

if (FALSE) { # \dontrun{
geno_table <- import_amrfp(ecoli_geno_raw, "Name")
head(ecoli_ast)
soloPPV_cipro <- solo_ppv_analysis(
  geno_table = geno_table,
  pheno_table = ecoli_ast,
  antibiotic = "Ciprofloxacin",
  drug_class_list = c("Quinolones"),
  sir_col = "Resistance phenotype"
)
soloPPV_cipro$solo_stats
soloPPV_cipro$combined_plot
} # }