summaryrefslogtreecommitdiff
path: root/CakeModel.R
blob: a93d7af7ce0553e507a4a910d9b67200c9e068cc (plain) (blame)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
# Was Id: mkinmod.R 71 2010-09-12 01:13:36Z jranke 
# $Id: CakeModel.R 216 2011-07-05 14:35:03Z nelr $

# The CAKE R modules are based on mkin
# Portions Johannes Ranke, 2010
# Contact: mkin-devel@lists.berlios.de

# This version has been modified to parameterise SFO as k and flow fractions
# Modifications developed by Tessella Plc for Syngenta: Copyright (C) 2011  Syngenta
# Tessella Project Reference: 6245

#    This program is free software: you can redistribute it and/or modify
#    it under the terms of the GNU General Public License as published by
#    the Free Software Foundation, either version 3 of the License, or
#    (at your option) any later version.
# 
#    This program is distributed in the hope that it will be useful,
#    but WITHOUT ANY WARRANTY; without even the implied warranty of
#    MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
#    GNU General Public License for more details.
# 
#    You should have received a copy of the GNU General Public License
#    along with this program.  If not, see <http://www.gnu.org/licenses/>.”

CakeModel <- function(...)
{
  spec <- list(...)
  obs_vars <- names(spec)

  # The returned model will be a list of character vectors, containing
  # differential equations, parameter names and a mapping from model variables
  # to observed variables. If possible, a matrix representation of the 
  # differential equations is included
  parms <- vector()
  diffs <- vector()
  map <- list()
  if(spec[[1]]$type %in% c("FOMC", "DFOP", "HS")) {
    mat = FALSE 
    if(!is.null(spec[[1]]$to)) {
      message <- paste("Only constant formation fractions over time are implemented.",
        "Depending on the reason for the time dependence of degradation, this may be unrealistic",
        sep="\n")
      warning(message)
    } else message <- "ok"
  } else mat = TRUE
  
  mat = FALSE # XYZZY Not implemented yet assuming it should be
  nlt = list()

  # Establish list of differential equations
  for (varname in obs_vars)
  {
    if(is.null(spec[[varname]]$type)) stop(
      "Every argument to mkinmod must be a list containing a type component")
    if(!spec[[varname]]$type %in% c("SFO", "FOMC", "DFOP", "HS", "SFORB")) stop(
      "Available types are SFO, FOMC, DFOP, HS and SFORB only")
    new_parms <- vector()

    # New (sub)compartments (boxes) needed for the model type
    new_boxes <- switch(spec[[varname]]$type,
      SFO = varname,
      FOMC = varname,
      DFOP = varname,
      HS = varname,
      SFORB = paste(varname, c("free", "bound"), sep="_")
    )
    map[[varname]] <- new_boxes
    names(map[[varname]]) <- rep(spec[[varname]]$type, length(new_boxes))

    # Start a new differential equation for each new box
    new_diffs <- paste("d_", new_boxes, " =", sep="")

    # Turn on sink if not specified otherwise
    if(is.null(spec[[varname]]$sink)) spec[[varname]]$sink <- TRUE
    
    #@@@ADD SFO k HERE !!!!!!!!!!!!!
    # Construct and add SFO term and add SFO parameters if needed
    if(spec[[varname]]$type == "SFO") {
      # From p. 53 of the FOCUS kinetics report
      k_term <- paste("k", new_boxes[[1]], sep="_")
      nonlinear_term <- paste(k_term, new_boxes[[1]], sep=" * ")
      spec[[varname]]$nlt<-nonlinear_term
      new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
      new_parms <- k_term
      ff <- vector()
    } 

    # Construct and add FOMC term and add FOMC parameters if needed
    if(spec[[varname]]$type == "FOMC") {
      if(match(varname, obs_vars) != 1) {
        stop("Type FOMC is only possible for the first compartment, which is assumed to be the source compartment")
      }
#      if(spec[[varname]]$sink == FALSE) {
#        stop("Turning off the sink for the FOMC model is not implemented")
#      }
      # From p. 53 of the FOCUS kinetics report
      nonlinear_term <- paste("(alpha/beta) * ((time/beta) + 1)^-1 *", new_boxes[[1]])
      spec[[varname]]$nlt<-nonlinear_term
      new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
      new_parms <- c("alpha", "beta")
      ff <- vector()
    } 

    # Construct and add DFOP term and add DFOP parameters if needed
    if(spec[[varname]]$type == "DFOP") {
      if(match(varname, obs_vars) != 1) {
        stop("Type DFOP is only possible for the first compartment, which is assumed to be the source compartment")
      }
#      if(spec[[varname]]$sink == FALSE) {
#        stop("Turning off the sink for the DFOP model is not implemented")
#      }
      # From p. 57 of the FOCUS kinetics report
      nonlinear_term <- paste("((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time))) *", new_boxes[[1]])
      spec[[varname]]$nlt<-nonlinear_term
      new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
      new_parms <- c("k1", "k2", "g")
      ff <- vector()
    } 

    # Construct and add HS term and add HS parameters if needed
    if(spec[[varname]]$type == "HS") {
      if(match(varname, obs_vars) != 1) {
        stop("Type HS is only possible for the first compartment, which is assumed to be the source compartment")
      }
#      if(spec[[varname]]$sink == FALSE) {
#        stop("Turning off the sink for the HS model is not implemented")
#      }
      # From p. 55 of the FOCUS kinetics report
#      nonlinear_term <- paste("ifelse(time <= tb, k1, k2)", "*", new_boxes[[1]])
      nonlinear_term <- paste("((k1 - k2) / ( 1 + exp( 10*(time - tb) ) ) + k2)", "*", new_boxes[[1]])
      spec[[varname]]$nlt<-nonlinear_term
      new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
      new_parms <- c("k1", "k2", "tb")
      ff <- vector()
    } 

    # Construct terms for transfer to sink and add if appropriate

    #@@@@ REMOVE THIS ?????
    if(spec[[varname]]$sink) {
      # Add first-order sink term to first (or only) box for SFO and SFORB
#      if(spec[[varname]]$type %in% c("SFO", "SFORB")) {
      if(spec[[varname]]$type == "SFORB") {
        k_compound_sink <- paste("k", new_boxes[[1]], "sink", sep="_")
        sink_term <- paste("-", k_compound_sink, "*", new_boxes[[1]])
        new_diffs[[1]] <- paste(new_diffs[[1]], sink_term)
        new_parms <- k_compound_sink
      }
    }
   
    # Add reversible binding if appropriate
    if(spec[[varname]]$type == "SFORB") {
      k_free_bound <- paste("k", varname, "free", "bound", sep="_")      
      k_bound_free <- paste("k", varname, "bound", "free", sep="_")      
      reversible_binding_terms <- c(
        paste("-", k_free_bound, "*", new_boxes[[1]], "+", k_bound_free, "*", new_boxes[[2]]),
        paste("+", k_free_bound, "*", new_boxes[[1]], "-", k_bound_free, "*", new_boxes[[2]]))
      new_diffs <- paste(new_diffs, reversible_binding_terms)
      new_parms <- c(new_parms, k_free_bound, k_bound_free)
    } 

    # Add observed variable to model
    parms <- c(parms, new_parms)
    names(new_diffs) <- new_boxes
    diffs <- c(diffs, new_diffs)
  }
  # Transfer between compartments
  for (varname in obs_vars) {
    to <- spec[[varname]]$to
    if(!is.null(to)) {
      origin_box <- switch(spec[[varname]]$type,
        SFO = varname,
        FOMC = varname,
        DFOP = varname,
        HS = varname,
        SFORB = paste(varname, "free", sep="_"))
      fraction_left <- NULL
      for (target in to) {
        target_box <- switch(spec[[target]]$type,
          SFO = target,
          SFORB = paste(target, "free", sep="_"))
        # SFO is no longer special
        #if(spec[[varname]]$type %in% c("SFO", "SFORB")) {
        if(spec[[varname]]$type == "SFORB") {
          k_from_to <- paste("k", origin_box, target_box, sep="_")
          diffs[[origin_box]] <- paste(diffs[[origin_box]], "-", 
            k_from_to, "*", origin_box)
          diffs[[target_box]] <- paste(diffs[[target_box]], "+", 
            k_from_to, "*", origin_box)
          parms <- c(parms, k_from_to)
        }
        # Handle SFO like the others
#        if(spec[[varname]]$type %in% c("FOMC", "DFOP", "HS")) {
        if(spec[[varname]]$type %in% c("FOMC", "DFOP", "HS", "SFO")) {
          if ( length(to)==1 && !spec[[varname]]$sink ) {
            # There is only one output, so no need for any flow fractions. Just add the whole flow from the parent
            diffs[[target_box]] <- paste(diffs[[target_box]], "+", spec[[varname]]$nlt)
          } else {
            fraction_to_target = paste("f", varname, "to", target, sep="_")
            fraction_not_to_target = paste("(1 - ", fraction_to_target, ")", sep="")
            if(is.null(fraction_left)) {
              fraction_really_to_target = fraction_to_target
              fraction_left = fraction_not_to_target
            } else {
              # If this is the last output and there is no sink, it gets what's left
              if ( target==tail(to,1) && !spec[[varname]]$sink ) {
                 fraction_really_to_target = fraction_left
              } else {
# (1-fa)fb version
#                 fraction_really_to_target = paste(fraction_left, " * ", fraction_to_target, sep="")
#                 fraction_left = paste(fraction_left, " * ", fraction_not_to_target, sep="")
# fb version
                 fraction_really_to_target = fraction_to_target
                 fraction_left = paste(fraction_left, " - ", fraction_to_target, sep="")
              }
            }
            ff[target_box] = fraction_really_to_target
            diffs[[target_box]] <- paste(diffs[[target_box]], "+", ff[target_box], "*", spec[[varname]]$nlt)
            # Add the flow fraction parameter (if it exists)
            if ( target!=tail(to,1) || spec[[varname]]$sink ) {
              parms <- c(parms, fraction_to_target)
            }
          }
        }
      }
    }
  }
  model <- list(diffs = diffs, parms = parms, map = map)

  # Create coefficient matrix if appropriate
  if (mat) {
    boxes <- names(diffs)
    n <- length(boxes)
    m <- matrix(nrow=n, ncol=n, dimnames=list(boxes, boxes))
    for (from in boxes) {
      for (to in boxes) {
        if (from == to) {
          #@@@@ OMIT NEXT LINE? !!!!!
          k.candidate = paste("k", from, c(boxes, "sink"), sep="_")
          k.candidate = sub("free.*bound", "free_bound", k.candidate)
          k.candidate = sub("bound.*free", "bound_free", k.candidate)
          k.effective = intersect(model$parms, k.candidate)
          m[from,to] = ifelse(length(k.effective) > 0,
              paste("-", k.effective, collapse = " "), "0")
        } else {
          k.candidate = paste("k", from, to, sep="_")
          k.candidate = sub("free.*bound", "free_bound", k.candidate)
          k.candidate = sub("bound.*free", "bound_free", k.candidate)
          k.effective = intersect(model$parms, k.candidate)
          m[to, from] = ifelse(length(k.effective) > 0,
              k.effective, "0")
        }
      }
    }
    model$coefmat <- m
  }

  if (exists("ff")) model$ff = ff
  class(model) <- "mkinmod"
  invisible(model)
}

Contact - Imprint