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Drug sensitivity calling using waterfall plots

Source: R/callingWaterfall.R
callingWaterfall.Rd

  1. Sensitivity calls were made using one of IC50, ActArea or Amax

Usage

callingWaterfall(
  x,
  type = c("IC50", "AUC", "AMAX"),
  intermediate.fold = c(4, 1.2, 1.2),
  cor.min.linear = 0.95,
  name = "Drug",
  plot = FALSE
)

Arguments

x

What type of object does this take in?

type

ic50: IC50 values in micro molar (positive values) actarea: Activity Area, that is area under the drug activity curve (positive values) amax: Activity at max concentration (positive values)

intermediate.fold

vector of fold changes used to define the intermediate sensitivities for ic50, actarea and amax respectively

cor.min.linear

numeric The minimum linear correlation to require?

name

character The name of the output to use in plot

plot

boolean Whether to plot the results

Value

factor Containing the drug sensitivity status of each sample.

Details

  1. Sort log IC50s (or ActArea or Amax) of the samples to generate a “waterfall distribution”

  2. Identify cutoff:

3.1 If the waterfall distribution is non-linear (pearson cc to the linear fit <=0.95), estimate the major inflection point of the log IC50 curve as the point on the curve with the maximal distance to a line drawn between the start and end points of the distribution.

3.2 If the waterfall distribution appears linear (pearson cc to the linear fit > 0.95), then use the median IC50 instead.

  1. Samples within a 4-fold IC50 (or within a 1.2-fold ActArea or 20% Amax difference) difference centered around this inflection point are classified as being “intermediate”, samples with lower IC50s (or ActArea/Amax values) than this range are defined as sensitive, and those with IC50s (or ActArea/Amax) higher than this range are called “insensitive”.

  2. Require at least x sensitive and x insensitive samples after applying these criteria (x=5 in our case).

Examples

# Dummy example
1 + 1
#> [1] 2