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Derive TDI parameters from enzyme activity data

tdimod.Rd

[Experimental]

Usage

tdimod(x, object = NULL)

Arguments

x

In vitro data as data frame. The following columns are expected:

  • TIME Duration of Pre-incubation with the precipitant and NADPH in minutes

  • CONC Precipitant concentration in uM

  • ACT Enzyme activity in percent

object

The DDI target object as character or NULL.

Value

A list with the following items:

  • data The input data with linear models of ACT over TIME by CONC.

  • kobs The kobs parameters by precipitant concentration.

  • kobs_plot A ggplot object showing the kobs fit to the ACT data.

  • tdi_param The TDI parameters, Kinact and KI, derived from an Emax model of kobs over CONC.

  • tdi_plot A ggplot object showing the Emnax modeling of kobs over CONC.

Details

kobs is fitted to the enzyme activity data as a first-order process for each inhibitor concentration. kinact (the maximal inhibition rate) and KI (inhibitor concentration at the half-maximal kobs) are fitted from kobs over inhibitor concentration using a Emax model.

Examples

tdimod(examplinib_in_vitro_tdi)
#> $data
#> # A tibble: 7 × 4
#> # Rowwise:  CONC
#>     CONC               data mod    modpar          
#>    <dbl> <list<tibble[,3]>> <list> <list>          
#> 1   0.2             [6 × 3] <lm>   <tibble [2 × 5]>
#> 2   0.66            [6 × 3] <lm>   <tibble [2 × 5]>
#> 3   2               [6 × 3] <lm>   <tibble [2 × 5]>
#> 4   6.66            [6 × 3] <lm>   <tibble [2 × 5]>
#> 5  20               [6 × 3] <lm>   <tibble [2 × 5]>
#> 6  50               [6 × 3] <lm>   <tibble [2 × 5]>
#> 7 100               [6 × 3] <lm>   <tibble [2 × 5]>
#> 
#> $kobs
#> # A tibble: 7 × 4
#> # Groups:   CONC [7]
#>     CONC       kobs std.error  p.value
#>    <dbl>      <dbl>     <dbl>    <dbl>
#> 1   0.2  -0.00133     0.00163 0.459   
#> 2   0.66 -0.0000905   0.00147 0.954   
#> 3   2    -0.000668    0.00107 0.566   
#> 4   6.66  0.00170     0.00182 0.402   
#> 5  20     0.0174      0.00346 0.00732 
#> 6  50     0.0201      0.00266 0.00165 
#> 7 100     0.0291      0.00228 0.000218
#> 
#> $kobs_plot

#> 
#> $tdi_param
#> # A tibble: 2 × 5
#>   term   estimate std.error statistic p.value
#>   <chr>     <dbl>     <dbl>     <dbl>   <dbl>
#> 1 kinact   0.0412   0.00987      4.17 0.00870
#> 2 kI      43.6     24.0          1.82 0.129  
#> 
#> $tdi_plot

#>