The Curvep function to process one set of concentration-response data

The relationship between concentration and response has to be 1 to 1. The function is the backbone of run_rcurvep() and combi_run_rcurvep().

Usage

curvep(
  Conc,
  Resp,
  Mask = NULL,
  TRSH = 15,
  RNGE = -100,
  MXDV = 5,
  CARR = 0,
  BSFT = 3,
  USHP = 4,
  TrustHi = FALSE,
  StrictImp = TRUE,
  DUMV = -999,
  TLOG = -24,
  ...
)

Arguments

Conc: Array of concentrations, e.g., in Molar units, can be log-transformed, in which case internal log-transformation is skipped.
Resp: Array of responses at corresponding concentrations, e.g., raw measurements or normalized to controls.
Mask: array of 1/0 flags indicating invalidated measurements (default = NULL).
TRSH: Base(zero-)line threshold (default = 15).
RNGE: Target range of responses (default = -100).
MXDV: Maximum allowed deviation from monotonicity (default = 5).
CARR: Carryover detection threshold (default = 0, analysis skipped if set to 0). CARR is defined as a maximum expected magnitude of artifact response; it should be higher than baseline TRSH value, curves with active signal above baseline but below CARR at first few doses will be considered as carry-over cases. Also, curves with responses above CARR are treated as potent.
BSFT: For baseline shift issue, min.#points to detect baseline shift (default = 3, analysis skipped if set to 0).
USHP: For u-shape curves, min.#points to avoid flattening (default = 4, analysis skipped if set to 0).
TrustHi: For equal sets of corrections, trusts those retaining measurements at high concentrations (default = FALSE).
StrictImp: It prevents extrapolating over concentration-range boundaries; used for POD, ECxx etc (default = TRUE).
DUMV: A dummy value, default = -999.
TLOG: A scaling factor for calculating the wAUC, default = -24.
...: allow other parameters to pass

Value

A list with corrected concentration-response measurements and several calculated curve metrics.

resp: corrected responses
corr: flags for corrections
ECxx: effective concentration values at various thresholds
Cxx: concentrations for various absolute response levels
Emax: maximum effective concentration, slope of the mid-curve (b/w EC25 and EC75)
wConc: response-weighted concentration
wResp: concentration-weighed response
POD: point-of-departure (first concentration with response >TRSH)
AUC: area-under-curve (in units of log-concentration X response)
wAUC: AUC weighted by concentration range and POD / TLOG (-24)
wAUC_pre: AUC weighted by concentration range and POD
nCorrected: number of points corrected (basically, sum of flags in corr)
Comments: warning and notes about the dose-response curve
Settings: input parameters for this run

References

Sedykh A, Zhu H, Tang H, Zhang L, Richard A, Rusyn I, Tropsha A (2011). “Use of in vitro HTS-derived concentration-response data as biological descriptors improves the accuracy of QSAR models of in vivo toxicity.” Environmental health perspectives, 119(3), 364-370. ISSN 0091-6765, doi:10.1289/ehp.1002476 .
Sedykh A (2016). “CurveP Method for Rendering High-Throughput Screening Dose-Response Data into Digital Fingerprints.” Methods in molecular biology (Clifton, N.J.), 1473. ISSN 1064-3745, doi:10.1007/978-1-4939-6346-1_14 .

Examples


curvep(Conc = c(-8, -7, -6, -5, -4) , Resp = c(0, -3, -5, -15, -30))
#> $resp
#> [1]   0   0   0 -15 -30
#> 
#> $corr
#> [1] 0 0 0 0 0
#> 
#> $ECxx
#>  [1] -5.98 -5.90 -5.80 -5.60 -5.50 -5.00 -4.50 -4.40 -4.20 -4.10 -4.02 -4.00
#> 
#> $Cxx
#>  [1]   -5.933333   -5.666667   -5.333333   -4.666667   -4.333333 -999.000000
#>  [7] -999.000000 -999.000000 -999.000000 -999.000000 -999.000000 -999.000000
#> 
#> $xx
#>  [1]   1   5  10  20  25  50  75  80  90  95  99 100
#> 
#> $Emax
#> [1] -30
#> 
#> $slope
#> [1] -15
#> 
#> $wConc
#> [1] -4.333333
#> 
#> $wResp
#> [1] -6.5
#> 
#> $EC50
#> [1] -5
#> 
#> $C50
#> [1] -999
#> 
#> $POD
#> [1] -5
#> 
#> $AUC
#> [1] -30
#> 
#> $wAUC
#> [1] -1.263158
#> 
#> $wAUC_prev
#> [1] -37.5
#> 
#> $nCorrected
#> [1] 0
#> 
#> $Comments
#> [1] "OK"
#> 
#> $Settings
#> $Settings$TRSH
#> [1] 15
#> 
#> $Settings$RNGE
#> [1] -100
#> 
#> $Settings$MXDV
#> [1] 5
#> 
#> $Settings$CARR
#> [1] 0
#> 
#> $Settings$BSFT
#> [1] 3
#> 
#> $Settings$USHP
#> [1] 4
#> 
#> $Settings$TrustHi
#> [1] FALSE
#> 
#> $Settings$StrictImp
#> [1] TRUE
#> 
#> $Settings$DUMV
#> [1] -999
#> 
#> $Settings$TLOG
#> [1] -24
#> 
#>