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
|
mkinmod <- 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
parms <- vector()
diffs <- vector()
map <- 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", "SFORB")) stop("Available types are SFO, FOMC and SFORB only")
new_parms <- vector()
# New (sub)compartments (boxes) needed for the model type
new_boxes <- switch(spec[[varname]]$type,
SFO = varname,
FOMC = varname,
SFORB = paste(varname, c("free", "bound"), sep="_")
)
map[[varname]] <- new_boxes
names(map[[varname]]) <- rep(spec[[varname]]$type, length(new_boxes))
# Start a new differential equation for each new box
new_diffs <- paste("d_", new_boxes, " =", sep="")
# Construct terms for transfer to sink and add if appropriate
if(is.null(spec[[varname]]$sink)) spec[[varname]]$sink <- TRUE
if(spec[[varname]]$sink) {
# Add first-order sink term to first (or only) box for SFO and SFORB models
if(spec[[varname]]$type %in% c("SFO", "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
}
if(spec[[varname]]$type == "FOMC") {
if(match(varname, obs_vars) != 1) {
stop("Type FOMC is only allowed for the first compartment, which is assumed to be the source compartment")
}
# From p. 53 of the FOCUS kinetics report
fomc_term <- paste("(alpha/beta) * ((time/beta) + 1)^-1 *", new_boxes[[1]])
new_diffs[[1]] <- paste(new_diffs[[1]], "-", fomc_term)
new_parms <- c("alpha", "beta")
}
}
# Add reversible binding if appropriate
if(spec[[varname]]$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,
SFORB = paste(varname, "free", sep="_"))
fraction_left <- NULL
for (target in to) {
target_box <- switch(spec[[target]]$type,
SFO = target,
SFORB = paste(target, "free", sep="_"))
if(spec[[varname]]$type %in% c("SFO", "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)
}
if(spec[[varname]]$type == "FOMC") {
fraction_to_target = paste("f_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 {
fraction_really_to_target = paste(fraction_left, " * ", fraction_to_target, sep="")
fraction_left = paste(fraction_left, " * ", fraction_not_to_target, sep="")
}
diffs[[target_box]] <- paste(diffs[[target_box]], "+", fraction_really_to_target, "*", fomc_term)
parms <- c(parms, fraction_to_target)
}
}
}
}
model <- list(diffs = diffs, parms = parms, map = map)
class(model) <- "mkinmod"
invisible(model)
}
|
