#' Estimation of parameter distributions from mmkin row objects #' #' This function sets up and attempts to fit a mixed effects model to #' an mmkin row object. An mmkin row object is essentially a list of mkinfit #' objects that have been obtained by fitting the same model to a list of #' datasets. #' #' @param object An mmkin row object containing several fits of the same model to different datasets #' @import nlme #' @importFrom purrr map_dfr #' @return A named vector containing mean values of the fitted degradation model parameters #' @rdname nlme #' @examples #' sampling_times = c(0, 1, 3, 7, 14, 28, 60, 90, 120) #' m_SFO <- mkinmod(parent = mkinsub("SFO")) #' d_SFO_1 <- mkinpredict(m_SFO, #' c(k_parent_sink = 0.1), #' c(parent = 98), sampling_times) #' d_SFO_1_long <- mkin_wide_to_long(d_SFO_1, time = "time") #' d_SFO_2 <- mkinpredict(m_SFO, #' c(k_parent_sink = 0.05), #' c(parent = 102), sampling_times) #' d_SFO_2_long <- mkin_wide_to_long(d_SFO_2, time = "time") #' d_SFO_3 <- mkinpredict(m_SFO, #' c(k_parent_sink = 0.02), #' c(parent = 103), sampling_times) #' d_SFO_3_long <- mkin_wide_to_long(d_SFO_3, time = "time") #' #' d1 <- add_err(d_SFO_1, function(value) 3, n = 1) #' d2 <- add_err(d_SFO_2, function(value) 2, n = 1) #' d3 <- add_err(d_SFO_3, function(value) 4, n = 1) #' ds <- c(d1 = d1, d2 = d2, d3 = d3) #' #' f <- mmkin("SFO", ds, cores = 1, quiet = TRUE) #' mean_dp <- mean_degparms(f) #' grouped_data <- nlme_data(f) #' nlme_f <- nlme_function(f) #' #' library(nlme) #' m_nlme <- nlme(value ~ nlme_f(name, time, parent_0, log_k_parent_sink), #' data = grouped_data, #' fixed = parent_0 + log_k_parent_sink ~ 1, #' random = pdDiag(parent_0 + log_k_parent_sink ~ 1), #' start = mean_dp) #' summary(m_nlme) #' #' \dontrun{ #' Test on some real data #' ds_2 <- lapply(experimental_data_for_UBA_2019[6:10], #' function(x) x$data[c("name", "time", "value")]) #' m_sfo_sfo <- mkinmod(parent = mkinsub("SFO", "A1"), #' A1 = mkinsub("SFO"), use_of_ff = "min") #' m_sfo_sfo_ff <- mkinmod(parent = mkinsub("SFO", "A1"), #' A1 = mkinsub("SFO"), use_of_ff = "max") #' m_fomc_sfo <- mkinmod(parent = mkinsub("FOMC", "A1"), #' A1 = mkinsub("SFO")) #' m_dfop_sfo <- mkinmod(parent = mkinsub("DFOP", "A1"), #' A1 = mkinsub("SFO")) #' m_sforb_sfo <- mkinmod(parent = mkinsub("SFORB", "A1"), #' A1 = mkinsub("SFO")) #' #' f_2 <- mmkin(list("SFO-SFO" = m_sfo_sfo, #' "SFO-SFO-ff" = m_sfo_sfo_ff, #' "FOMC-SFO" = m_fomc_sfo, #' "DFOP-SFO" = m_dfop_sfo, #' "SFORB-SFO" = m_sforb_sfo), #' ds_2) #' #' grouped_data_2 <- nlme_data(f_2["SFO-SFO", ]) #' #' mean_dp_sfo_sfo <- mean_degparms(f_2["SFO-SFO", ]) #' mean_dp_sfo_sfo_ff <- mean_degparms(f_2["SFO-SFO-ff", ]) #' mean_dp_fomc_sfo <- mean_degparms(f_2["FOMC-SFO", ]) #' mean_dp_dfop_sfo <- mean_degparms(f_2["DFOP-SFO", ]) #' mean_dp_sforb_sfo <- mean_degparms(f_2["SFORB-SFO", ]) #' #' nlme_f_sfo_sfo <- nlme_function(f_2["SFO-SFO", ]) #' nlme_f_sfo_sfo_ff <- nlme_function(f_2["SFO-SFO-ff", ]) #' nlme_f_fomc_sfo <- nlme_function(f_2["FOMC-SFO", ]) #' #' # Allowing for correlations between random effects leads to non-convergence #' f_nlme_sfo_sfo <- nlme(value ~ nlme_f_sfo_sfo(name, time, #' parent_0, log_k_parent_sink, log_k_parent_A1, log_k_A1_sink), #' data = grouped_data_2, #' fixed = parent_0 + log_k_parent_sink + log_k_parent_A1 + log_k_A1_sink ~ 1, #' random = pdDiag(parent_0 + log_k_parent_sink + log_k_parent_A1 + log_k_A1_sink ~ 1), #' start = mean_dp_sfo_sfo) #' #' # The same model fitted with transformed formation fractions does not converge #' f_nlme_sfo_sfo_ff <- nlme(value ~ nlme_f_sfo_sfo_ff(name, time, #' parent_0, log_k_parent, log_k_A1, f_parent_ilr_1), #' data = grouped_data_2, #' fixed = parent_0 + log_k_parent + log_k_A1 + f_parent_ilr_1 ~ 1, #' random = pdDiag(parent_0 + log_k_parent + log_k_A1 + f_parent_ilr_1 ~ 1), #' start = mean_dp_sfo_sfo_ff) #' #' # It does converge with this version of reduced random effects #' f_nlme_sfo_sfo_ff <- nlme(value ~ nlme_f_sfo_sfo_ff(name, time, #' parent_0, log_k_parent, log_k_A1, f_parent_ilr_1), #' data = grouped_data_2, #' fixed = parent_0 + log_k_parent + log_k_A1 + f_parent_ilr_1 ~ 1, #' random = pdDiag(parent_0 + log_k_parent ~ 1), #' start = mean_dp_sfo_sfo_ff) #' #' f_nlme_fomc_sfo <- nlme(value ~ nlme_f_fomc_sfo(name, time, #' parent_0, log_alpha, log_beta, log_k_A1, f_parent_ilr_1), #' data = grouped_data_2, #' fixed = parent_0 + log_alpha + log_beta + log_k_A1 + f_parent_ilr_1 ~ 1, #' random = pdDiag(parent_0 + log_alpha + log_beta + log_k_A1 + f_parent_ilr_1 ~ 1), #' start = mean_dp_fomc_sfo) #' #' # DFOP-SFO and SFORB-SFO did not converge with full random effects #' #' anova(f_nlme_fomc_sfo, f_nlme_sfo_sfo) #' } #' @export mean_degparms <- function(object) { if (nrow(object) > 1) stop("Only row objects allowed") p_mat_start_trans <- sapply(object, parms, transformed = TRUE) mean_degparm_names <- setdiff(rownames(p_mat_start_trans), names(object[[1]]$errparms)) res <- apply(p_mat_start_trans[mean_degparm_names, ], 1, mean) return(res) } #' @rdname nlme #' @importFrom purrr map_dfr #' @return A groupedData data object #' @export nlme_data <- function(object) { if (nrow(object) > 1) stop("Only row objects allowed") ds_names <- colnames(object) ds_list <- lapply(object, function(x) x$data[c("time", "variable", "observed")]) names(ds_list) <- ds_names ds_nlme <- purrr::map_dfr(ds_list, function(x) x, .id = "ds") ds_nlme$variable <- as.character(ds_nlme$variable) ds_nlme_renamed <- data.frame(ds = ds_nlme$ds, name = ds_nlme$variable, time = ds_nlme$time, value = ds_nlme$observed, stringsAsFactors = FALSE) ds_nlme_grouped <- groupedData(value ~ time | ds, ds_nlme_renamed) return(ds_nlme_grouped) } #' @rdname nlme #' @return A function that can be used with nlme #' @export nlme_function <- function(object) { if (nrow(object) > 1) stop("Only row objects allowed") mkin_model <- object[[1]]$mkinmod degparm_names <- names(mean_degparms(object)) # Inspired by https://stackoverflow.com/a/12983961/3805440 # and https://stackoverflow.com/a/26280789/3805440 model_function_alist <- replicate(length(degparm_names) + 2, substitute()) names(model_function_alist) <- c("name", "time", degparm_names) model_function_body <- quote({ arg_frame <- as.data.frame(as.list((environment())), stringsAsFactors = FALSE) res_frame <- arg_frame[1:2] parm_frame <- arg_frame[-(1:2)] parms_unique <- unique(parm_frame) n_unique <- nrow(parms_unique) times_ds <- list() names_ds <- list() for (i in 1:n_unique) { times_ds[[i]] <- arg_frame[which(arg_frame[[3]] == parms_unique[i, 1]), "time"] names_ds[[i]] <- arg_frame[which(arg_frame[[3]] == parms_unique[i, 1]), "name"] } res_list <- lapply(1:n_unique, function(x) { transparms_optim <- unlist(parms_unique[x, , drop = TRUE]) parms_fixed <- object[[1]]$bparms.fixed odeini_optim_parm_names <- grep('_0$', names(transparms_optim), value = TRUE) odeini_optim <- transparms_optim[odeini_optim_parm_names] names(odeini_optim) <- gsub('_0$', '', odeini_optim_parm_names) odeini_fixed_parm_names <- grep('_0$', names(parms_fixed), value = TRUE) odeini_fixed <- parms_fixed[odeini_fixed_parm_names] names(odeini_fixed) <- gsub('_0$', '', odeini_fixed_parm_names) odeini <- c(odeini_optim, odeini_fixed)[names(mkin_model$diffs)] ode_transparms_optim_names <- setdiff(names(transparms_optim), odeini_optim_parm_names) odeparms_optim <- backtransform_odeparms(transparms_optim[ode_transparms_optim_names], mkin_model, transform_rates = object[[1]]$transform_rates, transform_fractions = object[[1]]$transform_fractions) odeparms_fixed_names <- setdiff(names(parms_fixed), odeini_fixed_parm_names) odeparms_fixed <- parms_fixed[odeparms_fixed_names] odeparms <- c(odeparms_optim, odeparms_fixed) out_wide <- mkinpredict(mkin_model, odeparms = odeparms, odeini = odeini, solution_type = object[[1]]$solution_type, outtimes = sort(unique(times_ds[[x]]))) out_array <- out_wide[, -1, drop = FALSE] rownames(out_array) <- as.character(unique(times_ds[[x]])) out_times <- as.character(times_ds[[x]]) out_names <- as.character(names_ds[[x]]) out_values <- mapply(function(times, names) out_array[times, names], out_times, out_names) return(as.numeric(out_values)) }) res <- unlist(res_list) return(res) }) model_function <- as.function(c(model_function_alist, model_function_body)) return(model_function) }