require(mkin) require(testthat) # Per default (on my box where I set NOT_CRAN) use all cores minus one if (identical(Sys.getenv("NOT_CRAN"), "true")) { n_cores <- parallel::detectCores() - 1 } else { n_cores <- 1 } # We are only allowed one core on travis, but they also set NOT_CRAN=true if (Sys.getenv("TRAVIS") != "") n_cores = 1 # On Windows we would need to make a cluster first if (Sys.info()["sysname"] == "Windows") n_cores = 1 # We set up some models and fits with nls for comparisons SFO_trans <- function(t, parent_0, log_k_parent_sink) { parent_0 * exp(- exp(log_k_parent_sink) * t) } SFO_notrans <- function(t, parent_0, k_parent_sink) { parent_0 * exp(- k_parent_sink * t) } f_1_nls_trans <- nls(value ~ SFO_trans(time, parent_0, log_k_parent_sink), data = FOCUS_2006_A, start = list(parent_0 = 100, log_k_parent_sink = log(0.1))) f_1_nls_notrans <- nls(value ~ SFO_notrans(time, parent_0, k_parent_sink), data = FOCUS_2006_A, start = list(parent_0 = 100, k_parent_sink = 0.1)) f_1_mkin_trans <- mkinfit("SFO", FOCUS_2006_A, quiet = TRUE) f_1_mkin_notrans <- mkinfit("SFO", FOCUS_2006_A, quiet = TRUE, transform_rates = FALSE) # mmkin object of parent fits for tests models <- c("SFO", "FOMC", "DFOP", "HS") fits <- suppressWarnings( # FOCUS A FOMC was, it seems, in testthat output mmkin(models, list(FOCUS_A = FOCUS_2006_A, FOCUS_C = FOCUS_2006_C, FOCUS_D = FOCUS_2006_D), quiet = TRUE, cores = n_cores)) # One metabolite SFO_SFO <- mkinmod(parent = mkinsub("SFO", to = "m1"), m1 = mkinsub("SFO"), use_of_ff = "min", quiet = TRUE) SFO_SFO.ff <- mkinmod(parent = mkinsub("SFO", to = "m1"), m1 = mkinsub("SFO"), use_of_ff = "max", quiet = TRUE) SFO_SFO.ff.nosink <- mkinmod( parent = mkinsub("SFO", "m1", sink = FALSE), m1 = mkinsub("SFO"), quiet = TRUE, use_of_ff = "max") FOMC_SFO <- mkinmod(parent = mkinsub("FOMC", to = "m1"), m1 = mkinsub("SFO"), quiet = TRUE) DFOP_SFO <- mkinmod(parent = mkinsub("DFOP", to = "m1"), m1 = mkinsub("SFO"), use_of_ff = "max", quiet = TRUE) # Avoid warning when fitting a dataset where zero value is removed FOCUS_D <- subset(FOCUS_2006_D, value != 0) f_sfo_sfo_desolve <- mkinfit(SFO_SFO, FOCUS_D, solution_type = "deSolve", quiet = TRUE) f_sfo_sfo_eigen <- mkinfit(SFO_SFO, FOCUS_D, solution_type = "eigen", quiet = TRUE) f_sfo_sfo.ff <- mkinfit(SFO_SFO.ff, FOCUS_D, quiet = TRUE) SFO_lin_a <- synthetic_data_for_UBA_2014[[1]]$data DFOP_par_c <- synthetic_data_for_UBA_2014[[12]]$data f_2_mkin <- mkinfit("DFOP", DFOP_par_c, quiet = TRUE) f_2_nls <- nls(value ~ SSbiexp(time, A1, lrc1, A2, lrc2), data = subset(DFOP_par_c, name == "parent")) f_2_anova <- lm(value ~ as.factor(time), data = subset(DFOP_par_c, name == "parent")) # Two metabolites m_synth_SFO_lin <- mkinmod( parent = mkinsub("SFO", "M1"), M1 = mkinsub("SFO", "M2"), M2 = mkinsub("SFO"), use_of_ff = "max", quiet = TRUE) m_synth_DFOP_par <- mkinmod(parent = mkinsub("DFOP", c("M1", "M2")), M1 = mkinsub("SFO"), M2 = mkinsub("SFO"), use_of_ff = "max", quiet = TRUE) fit_nw_1 <- mkinfit(m_synth_SFO_lin, SFO_lin_a, quiet = TRUE) # We know direct optimization is OK and direct is faster than the default d_3 fit_obs_1 <- mkinfit(m_synth_SFO_lin, SFO_lin_a, error_model = "obs", quiet = TRUE, error_model_algorithm = "direct") # We know threestep is OK, and threestep (and IRLS) is faster here fit_tc_1 <- mkinfit(m_synth_SFO_lin, SFO_lin_a, error_model = "tc", quiet = TRUE, error_model_algorithm = "threestep") # Mixed models data and fits sampling_times = c(0, 1, 3, 7, 14, 28, 60, 90, 120) n <- n_biphasic <- 15 log_sd <- 0.3 err_1 = list(const = 1, prop = 0.05) tc <- function(value) sigma_twocomp(value, err_1$const, err_1$prop) const <- function(value) 2 set.seed(123456) SFO <- mkinmod(parent = mkinsub("SFO")) k_parent = rlnorm(n, log(0.03), log_sd) set.seed(123456) ds_sfo <- lapply(1:n, function(i) { ds_mean <- mkinpredict(SFO, c(k_parent = k_parent[i]), c(parent = 100), sampling_times) add_err(ds_mean, tc, n = 1)[[1]] }) set.seed(123456) FOMC <- mkinmod(parent = mkinsub("FOMC")) fomc_pop <- list(parent_0 = 100, alpha = 2, beta = 8) fomc_parms <- as.matrix(data.frame( alpha = rlnorm(n, log(fomc_pop$alpha), 0.4), beta = rlnorm(n, log(fomc_pop$beta), 0.2))) set.seed(123456) ds_fomc <- lapply(1:3, function(i) { ds_mean <- mkinpredict(FOMC, fomc_parms[i, ], c(parent = 100), sampling_times) add_err(ds_mean, tc, n = 1)[[1]] }) set.seed(123456) DFOP <- mkinmod(parent = mkinsub("DFOP")) dfop_pop <- list(parent_0 = 100, k1 = 0.06, k2 = 0.015, g = 0.4) dfop_parms <- as.matrix(data.frame( k1 = rlnorm(n, log(dfop_pop$k1), log_sd), k2 = rlnorm(n, log(dfop_pop$k2), log_sd), g = plogis(rnorm(n, qlogis(dfop_pop$g), log_sd)))) set.seed(123456) ds_dfop <- lapply(1:n, function(i) { ds_mean <- mkinpredict(DFOP, dfop_parms[i, ], c(parent = dfop_pop$parent_0), sampling_times) add_err(ds_mean, const, n = 1)[[1]] }) set.seed(123456) HS <- mkinmod(parent = mkinsub("HS")) hs_pop <- list(parent_0 = 100, k1 = 0.08, k2 = 0.01, tb = 15) hs_parms <- as.matrix(data.frame( k1 = rlnorm(n, log(hs_pop$k1), log_sd), k2 = rlnorm(n, log(hs_pop$k2), log_sd), tb = rlnorm(n, log(hs_pop$tb), 0.1))) set.seed(123456) ds_hs <- lapply(1:10, function(i) { ds_mean <- mkinpredict(HS, hs_parms[i, ], c(parent = hs_pop$parent_0), sampling_times) add_err(ds_mean, const, n = 1)[[1]] }) set.seed(123456) DFOP_SFO <- mkinmod( parent = mkinsub("DFOP", "m1"), m1 = mkinsub("SFO"), quiet = TRUE) dfop_sfo_pop <- list(parent_0 = 100, k_m1 = 0.005, f_parent_to_m1 = 0.5, k1 = 0.05, k2 = 0.01, g = 0.5) syn_biphasic_parms <- as.matrix(data.frame( k1 = rlnorm(n_biphasic, log(dfop_sfo_pop$k1), log_sd), k2 = rlnorm(n_biphasic, log(dfop_sfo_pop$k2), log_sd), g = plogis(rnorm(n_biphasic, qlogis(dfop_sfo_pop$g), log_sd)), f_parent_to_m1 = plogis(rnorm(n_biphasic, qlogis(dfop_sfo_pop$f_parent_to_m1), log_sd)), k_m1 = rlnorm(n_biphasic, log(dfop_sfo_pop$k_m1), log_sd))) ds_biphasic_mean <- lapply(1:n_biphasic, function(i) { mkinpredict(DFOP_SFO, syn_biphasic_parms[i, ], c(parent = 100, m1 = 0), sampling_times) } ) set.seed(123456) ds_biphasic <- lapply(ds_biphasic_mean, function(ds) { add_err(ds, sdfunc = function(value) sqrt(err_1$const^2 + value^2 * err_1$prop^2), n = 1, secondary = "m1")[[1]] }) # Mixed model fits saemix_available <- FALSE if (requireNamespace("saemix", quietly = TRUE)) { if(packageVersion("saemix") >= "3.0") saemix_available <- TRUE } mmkin_sfo_1 <- mmkin("SFO", ds_sfo, quiet = TRUE, error_model = "tc", cores = n_cores) mmkin_dfop_1 <- mmkin("DFOP", ds_dfop, quiet = TRUE, cores = n_cores) mmkin_biphasic <- mmkin(list("DFOP-SFO" = DFOP_SFO), ds_biphasic, quiet = TRUE, cores = n_cores) mmkin_biphasic_mixed <- mixed(mmkin_biphasic) dfop_nlme_1 <- nlme(mmkin_dfop_1) nlme_biphasic <- nlme(mmkin_biphasic) if (saemix_available) { sfo_saem_1 <- saem(mmkin_sfo_1, quiet = TRUE, transformations = "saemix") dfop_saemix_1 <- saem(mmkin_dfop_1, quiet = TRUE, transformations = "mkin") dfop_saemix_2 <- saem(mmkin_dfop_1, quiet = TRUE, transformations = "saemix") saem_biphasic_m <- saem(mmkin_biphasic, transformations = "mkin", quiet = TRUE) saem_biphasic_s <- saem(mmkin_biphasic, transformations = "saemix", quiet = TRUE) } ds_uba <- lapply(experimental_data_for_UBA_2019[6:10], function(x) subset(x$data[c("name", "time", "value")])) names(ds_uba) <- paste("Dataset", 6:10) sfo_sfo_uba <- mkinmod(parent = mkinsub("SFO", "A1"), A1 = mkinsub("SFO"), quiet = TRUE) dfop_sfo_uba <- mkinmod(parent = mkinsub("DFOP", "A1"), A1 = mkinsub("SFO"), quiet = TRUE) f_uba_mmkin <- mmkin(list("SFO-SFO" = sfo_sfo_uba, "DFOP-SFO" = dfop_sfo_uba), ds_uba, quiet = TRUE, cores = n_cores) f_uba_dfop_sfo_mixed <- mixed(f_uba_mmkin[2, ]) if (saemix_available) { f_uba_sfo_sfo_saem <- saem(f_uba_mmkin["SFO-SFO", ], quiet = TRUE, transformations = "saemix") f_uba_dfop_sfo_saem <- saem(f_uba_mmkin["DFOP-SFO", ], quiet = TRUE, transformations = "saemix") }