curvep {Rcurvep}

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

Description

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)

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.

See Also

run_rcurvep() and combi_run_rcurvep()

Examples

curvep(Conc = c(-8, -7, -6, -5, -4) , Resp = c(0, -3, -5, -15, -30))