app made independent XL and metadata, functions roxygenized

This commit is contained in:
2026-05-13 15:08:12 +02:00
parent a4bdbe8f8c
commit 1555fe3b6c
2 changed files with 443 additions and 257 deletions
+5 -20
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@@ -1,23 +1,8 @@
dat <- data.frame(REF1=c(1.1,1.2,2.1,3,5,6,8.1,9), REF1=c(1.2,1.5,2.1,3.1,4.9,6.1,8.3,9.1),
TEST1=c(1,1.3,2.5,3.5,5.9,6.9,8.1,9.1), TEST2=c(1.4,1.2,2.6,3.4,5.8,6.7,8.6,9.3), log_dose=c(1,0,-1,-2,-3,-4,-5,-6))
all_l <- melt(data.frame(dat), id.vars="log_dose", variable.name="replname", value.name = "readout")
isRef <- rep(c(1,0),1,each=nrow(all_l)/2)
isSample <- rep(c(0,1),1,each=nrow(all_l)/2)
all_l2 <- cbind(all_l, isRef, isSample)
startlistmu <- list(as=1, bs=-1,cs=-3,
ds=10,at=1, bt=-1,
dt=10,r=0)
mu <- gsl_nls(fn = readout ~ as*isRef + at*isSample + (ds*isRef + dt*isSample - as*isRef - at*isSample)/
(1+isRef*exp(bs*(cs - log_dose)) + isSample*exp(bt*(cs-r*isSample-log_dose))),
data=all_l,
start=startlistmu,
control=gsl_nls_control(xtol=1e-6,ftol=1e-6, gtol=1e-6))
s_mu <- summary(mu)$coefficients[,1]
s_mu
################################################################################
# Test file for functions of plateflow
# F. Innerbichler
# 13.5.2026
################################################################################
CIRC <- data.frame(log_dose = c(-2.5,-2.5,-2.5, -3.2,-3.2,-3.2,-3.9,-3.9,-3.9,
+438 -237
View File
@@ -669,6 +669,66 @@ ANOVAlintests <- function(ro_new, circles, Lim, PureErrFlag) {
return(RET)
}
PlotLinPLA_FUNC <-function(circle, sigmoid, all_l2, pl_df, indS, indT) {
mLin <- gsl_nls(readout ~ (intS+r)*isSample + intS*isRef + k*log_dose,
data=circle,
start=list(intS = 0, k=1,r=0),
control = gsl_nls_control(xtol=1e-10,ftol=1e-10,gtol=1e-10))
# alternativ: modAB <- lm(readout ~ log_dose+isSample, circle)
sum_mLin <- summary(mLin)
log_dose <- unique(all_l2$log_dose)
seq_x <- seq(min(log_dose), max(log_dose),0.1)
SAMPLEtrue <- sigmoid[5] + (sigmoid[7]-sigmoid[5])/(1+exp(sigmoid[6]*((sigmoid[4]-sigmoid[8]-seq_x))))
REFtrue <- sigmoid[1] + (sigmoid[3]-sigmoid[1])/(1+exp(sigmoid[2]*((sigmoid[4]-seq_x))))
truePL_df <- cbind(seq_x,SAMPLEtrue, REFtrue)
p <- ggplot(all_l2,aes(x=log_dose,y=readout, color=factor(isRef))) +
geom_point() +
labs(title=paste("linear regression model", indS,indT), color="product") +
scale_colour_manual(labels = c("test","reference"), values=c("#C2173F","#4545BA")) +
ylim(min(all_l2$readout),max(all_l2$readout)) +
theme_bw()
p2 <- p + geom_line(data=pl_df,aes(x=lnC,y=plotS),color="#4545BA",
inherit.aes = F) +
geom_line(data=pl_df,aes(x=lnC,y=plotT),color="#C2173F",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="#C2173F", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="#4545BA", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("unrestricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
p3 <- p2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
# fit intercept for test and ref and common slope
pl_restS <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[2,1]*log_dose
pl_restT <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[3,1] + sum_mLin$coefficients[2,1]*log_dose
pl_rest <- data.frame(lnC=log_dose, plotS=pl_restS, plotT=pl_restT)
pr2 <- p + geom_line(data=pl_rest,aes(x=lnC,y=plotS),color="#4545BA",
inherit.aes = F) +
geom_line(data=pl_rest,aes(x=lnC,y=plotT),color="#C2173F",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="#C2173F", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="#4545BA", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("restricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
pr3 <- pr2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
return(grid.arrange(p3,pr3,nrow=1))
}
#' Calculates the potency of 4PL PLA of all models model
#'
#' The gradient method is used for calculating the potency for a restricted model, an unrestricteed model,
@@ -1247,7 +1307,7 @@ server <- function(input, output, session) {
verbatimTextOutput("sessioninfo"))
)
})
##### UI XL ----
output$Dataupload <- renderUI({
navbarPage(title="Information",
tabPanel(title = "Real data",
@@ -1312,11 +1372,11 @@ server <- function(input, output, session) {
),
column(8,
plotOutput("XLplot"),
DTOutput("pottab4plXL"),
plotOutput("diagnplot"),
DTOutput("EQtests"),
DTOutput("pottab4pl"),
DTOutput("pottab4plTrans"),
DTOutput("pottab4plTransXL"),
tableOutput("ANOVAXLS")
)
@@ -1335,7 +1395,6 @@ server <- function(input, output, session) {
mainPanel(
tabsetPanel(id="tabs",
tabPanel("linear PLA",
column(12,
htmlOutput("PureErrW3"),
tags$head(tags$style("#PureErrW3{color: red;
@@ -1348,7 +1407,7 @@ server <- function(input, output, session) {
tableOutput("SummaryModABu"),
h4("Restricted linear model (CSSI):"),
tableOutput("SummaryModAB"),
h3("Tests for linear PLA):"),
box(title="Suitability tests", status="primary",solidHeader = T, width=12,
DTOutput("TESTSlin")),
@@ -1357,9 +1416,10 @@ server <- function(input, output, session) {
h5("All other tests pass if p-value > 0.05"),
"SST CI for difference of slopes:",
tableOutput("SlopeDiffCI"),
h3("ANOVA for parallel line assay"),
DTOutput("ANOVAlin"))),
DTOutput("ANOVAlin"))
),
tabPanel("Report",
h4("Settings for report")
))
@@ -1396,9 +1456,9 @@ server <- function(input, output, session) {
##### UI Meta ----
output$fourPL <- renderUI({
navbarPage(title="4PL",
navbarPage(title="4PL+linear reg",
tabPanel("Analysis and Plots",
#sidebarLayout(
# sidebarPanel(
@@ -1410,7 +1470,7 @@ server <- function(input, output, session) {
tabsetPanel(id="tabs",
tabPanel("Settings",
h4("Settings of 4PL regression"),
div(checkboxInput("PureErr4pl", "Should pure error be used for calculation of CIs?", FALSE),
div(checkboxInput("PureErrMeta", "Should pure error be used for calculation of CIs?", FALSE),
style = "font-size: 24px !important;color: #C2173F"),
h4("User help"),
@@ -1472,7 +1532,10 @@ server <- function(input, output, session) {
sliderInput("outlU","outlier in upper asymptote", min=0, max=1.5,value=0, step=0.1)
),
h4("log-dilutions from settings above"),
verbatimTextOutput("logdil")
verbatimTextOutput("logdil"),
column(8,
box(title = "Simulated data per log-concentration", status="warning",solidHeader = T, width=12, "incl. mean, sd and CV%",
DT::dataTableOutput("ConctabMeta")))
#)
),
@@ -1487,7 +1550,7 @@ server <- function(input, output, session) {
tags$style(span(htmlOutput("PureErrW3"), style="color: red")),
htmlOutput("PureErrW3"),
plotOutput("plot", width = "80%"),
plotOutput("plot4plMeta", width = "80%"),
DTOutput("pottab4pl"),
"Footnote: test performed on relative CIs.",
@@ -1510,18 +1573,51 @@ server <- function(input, output, session) {
h5("SSE ... 'Pure error' in the SumSquares column"),
h5("RMSE ... Square root of the 'Residual Error' in the MeanSquares column"),
verbatimTextOutput("RMSE")
),
column(8,
box(title = "Simulated data per log-concentration", status="warning",solidHeader = T, width=12, "incl. mean, sd and CV%",
DT::dataTableOutput("Conctab")))
)
))
),
tabPanel("ln-transformed y",
h4("ln-transformed y-axis plots"),
plotOutput("plot4plTrans", width = "80%"),
plotOutput("plot4plTransMeta", width = "80%"),
DT::dataTableOutput("pottab4plTrans"),
),
tabPanel("linear regression",
h4("Evaluations from meta-data"),
htmlOutput("PureErrW3"),
tags$head(tags$style("#PureErrW3{color: red;
font-size: 16px;
font_style: italic;}")),
column(12,
plotOutput("plotLinMeta"),
"Delta method is used for potency CIs",
DTOutput("pottabMeta")
),
column(5,
h3("Tests for linear PLA:"),
box(title="Suitability tests", status="primary",solidHeader = T,collapsible=T, width=12,
DTOutput("TESTSlinMeta")),
h5("The estimate is the p-value of the test"),
h5("F-tests on regression, significance of slopes, and preparation need to have a p-value <0.05 to pass"),
h5("All other tests pass if p-value > 0.05"),
box(title="Unrestricted linear model (SSSI):", status="primary",solidHeader = T,collapsible=T, width=12,
tableOutput("SummaryModABuMeta")),
h4("Restricted linear model (CSSI):"),
box(title="Restricted linear model (CSSI):", status="primary",solidHeader = T,collapsible=T, width=12,
tableOutput("SummaryModABMeta"))
),
column(6,
h3("ANOVA for parallel line assay"),
box(title="ANOVA for simultated data", status="primary",solidHeader = T, collapsible=T, width=12,
DTOutput("ANOVAlinMeta")),
" CI for difference of slopes:",
tableOutput("SlopeDiffCIMeta"),
)
),
tabPanel("Report",
h4("Settings for report"),
downloadButton("downloadXLReport", label="Download PDF report", class="butt"),
@@ -1795,13 +1891,13 @@ server <- function(input, output, session) {
REP$DiagnTable <- DiagnTable
logpotest <- FITsTrans[[3]] #exp(confintd(mrlog, "r", method = "asymptotic")) # compParm(logpot, "c")
logpotuest <- FITsTrans[[4]] # exp(confintd(mulog, "r", method = "asymptotic")) # compParm(logpotu, "c")
logpotUest <- FITsTrans[[4]] # exp(confintd(mulog, "r", method = "asymptotic")) # compParm(logpotu, "c")
# Berechnung der Konfidenzintervalle (CI)
# logpotCI <- c(exp(Smrlog[5,1] - qt(0.975, nrow(all_1)-5) * Smrlog[5,2]), exp(Smrlog[5,1]), exp(Smrlog[5,1] + qt(0.975, nrow(all_1)-5) * Smrlog[5,2]))
colnames(logpotest) <- c("estimate", "lowerCI", "upperCI")
colnames(logpotuest) <- c("estimate", "lowerCI", "upperCI")
colnames(logpotUest) <- c("estimate", "lowerCI", "upperCI")
#browser()
cnXL <- colnames(XLdat2)
Filesample <- data.frame(Test = c("File name", "samples"), Test2=c(Dat$FileName, paste(cnXL[1], " vs ", cnXL[4])))
@@ -1839,8 +1935,7 @@ server <- function(input, output, session) {
coeffs_R <- coeffsMR # pot$coefficients
coeffs_R[5] <- coeffs_R[4] - coeffs_R[5]
names(coeffs_R) <- c("lower A", "slope", "upper A", "EC50 REF", "EC50 TEST")
# coeffs_R[4] <- log(coeffs_R[4])
# coeffs_R[5] <- log(coeffs_R[5])
# --- Ergebnistabelle: RESTRICTED ---
PLAAusw <- data.frame(
Information = c("model", "lower asymptote", "Hill's slope", "upper asymptote","EC50 Ref",
@@ -1856,7 +1951,7 @@ server <- function(input, output, session) {
REP$PLAausw <- PLAAusw
REP$PLBend <- PLAAusw2
# --- Koeffizienten-Extraktion ---
#### Koeffizienten-Extraktion ----
logcoeffs_R <- SRlog$coefficients[, 1] # logpot$coefficients
names(logcoeffs_R) <- c("lower A", "Hill's slope", "upper A", "EC50 REF","EC50 DIFF")
@@ -1867,7 +1962,7 @@ server <- function(input, output, session) {
"EC50 difference", "log relative potency",
"log lower CI", "log upper CI"),
Results = unlist(c("LOG RESTRICTED", round(logcoeffs_R, 3),
round(logpotest * 100, 3)))) # von gs1_nls
round(logpotest * 100, 3)))) # von gsl_nls
output$logcoeffs_r <- renderTable({ LogPLAAusw })
REP$LogPLAausw <- LogPLAAusw
@@ -1885,7 +1980,7 @@ server <- function(input, output, session) {
"relative potency", "lower CI", "upper CI"),
Results = unlist(c("LOG UNRESTRICTED", round(logcoeffs_UNR, 3),
round(logpotest * 100, 3)))) # von gs1_nls
round(logpotUest * 100, 3)))) # von gsl_nls
output$logcoeffs_unr <- renderTable({
LogUnrPLAAusw
@@ -1900,7 +1995,7 @@ server <- function(input, output, session) {
} else Dat$dilution <- exp(XLdat[,logI])
# --- Plot-Ausgabe ---
output$XLplot <- renderPlot({
plot_f(XLdat2, sigmoid = NULL, det_sig = coeffsMU, TransFlag=F)
plot_f(XLdat2, TransFlag=F)
})
REP$XLdat2 <- XLdat2
@@ -1967,82 +2062,82 @@ server <- function(input, output, session) {
})
#### updateSlider on XLSX ----
observe({
if (!is.null(Dat$potDiffXL)) {
updateSliderInput(session, "potencydiff",
value=round(as.numeric(Dat$potDiffXL[[1]]),5))
}
})
observeEvent(input$potencydiff, {
if (!is.null(Dat$potDiffXL)) {
updateSliderInput(session, "potencydiff",
value=round(as.numeric(input$potencydiff),5))
}
})
observe({
if (!is.null(Dat$ProzSD_XL)) {
updateSliderInput(session, "sdfacf",
value=round(as.numeric(Dat$ProzSD_XL[[1]]),5))
}
})
observeEvent(input$sdfac, {
if (!is.null(Dat$ProzSD_XL)) {
updateSliderInput(session, "sdfac",
value=round(as.numeric(Dat$ProzSD_XL[[1]]),5))
}
})
# observe({
# if (!is.null(Dat$potDiffXL)) {
# updateSliderInput(session, "potencydiff",
# value=round(as.numeric(Dat$potDiffXL[[1]]),5))
# }
# })
# observeEvent(input$potencydiff, {
# if (!is.null(Dat$potDiffXL)) {
# updateSliderInput(session, "potencydiff",
# value=round(as.numeric(input$potencydiff),5))
# }
# })
# observe({
# if (!is.null(Dat$ProzSD_XL)) {
# updateSliderInput(session, "sdfac",
# value=round(as.numeric(Dat$ProzSD_XL[[1]]),5))
# }
# })
# observeEvent(input$sdfac, {
# if (!is.null(Dat$ProzSD_XL)) {
# updateSliderInput(session, "sdfac",
# value=round(as.numeric(Dat$ProzSD_XL[[1]]),5))
# }
# })
#### updaterNumeric Input ----
observe({
if(!is.null(Dat$coeffs_UN)) {
updateNumericInput(session, "lowAsymptREF",
value=round(as.numeric(Dat$coeffs_UN[3]),5), min=0)
updateNumericInput(session, "lowAsymptTEST",
value=round(as.numeric(Dat$coeffs_UN[4]),5), min=0)
updateNumericInput(session, "uppAsymptREF",
value=round(as.numeric(Dat$coeffs_UN[5]),5), min=0)
updateNumericInput(session, "uppAsymptTEST",
value=round(as.numeric(Dat$coeffs_UN[6]),5), min=0)
updateNumericInput(session, "slopeREF",
value=round(as.numeric(Dat$coeffs_UN[1]),5))
updateNumericInput(session, "slopeTEST",
value=round(as.numeric(Dat$coeffs_UN[2]),5))
updateNumericInput(session, "EC50",
value=round(as.numeric(Dat$coeffs_UN[7]),5))
updateNumericInput(session, "potDiff",
value=round(as.numeric(Dat$coeffs_UN[7])- as.numeric(Dat$coeffs_UN[8]),5))
}
})
observe({
if(!is.null(Dat$dilution)) {
updateNumericInput(session, "CONC1",
value=as.numeric(Dat$dilution[1]))
updateNumericInput(session, "CONC2",
value=as.numeric(Dat$dilution[2]))
updateNumericInput(session, "CONC3",
value=as.numeric(Dat$dilution[3]))
updateNumericInput(session, "CONC4",
value=as.numeric(Dat$dilution[4]))
updateNumericInput(session, "CONC5",
value=as.numeric(Dat$dilution[5]))
updateNumericInput(session, "CONC6",
value=as.numeric(Dat$dilution[6]))
updateNumericInput(session, "CONC7",
value=as.numeric(Dat$dilution[7]))
updateNumericInput(session, "CONC8",
value=as.numeric(Dat$dilution[8]))
updateNumericInput(session, "CONC9",
value=as.numeric(Dat$dilution[9]))
updateNumericInput(session, "CONC10",
value=as.numeric(Dat$dilution[10]))
updateNumericInput(session, "CONC11",
value=as.numeric(Dat$dilution[11]))
updateNumericInput(session, "CONC12",
value=as.numeric(Dat$dilution[12]))
}
})
# observe({
# if(!is.null(Dat$coeffs_UN)) {
# updateNumericInput(session, "lowAsymptREF",
# value=round(as.numeric(Dat$coeffs_UN[3]),5), min=0)
# updateNumericInput(session, "lowAsymptTEST",
# value=round(as.numeric(Dat$coeffs_UN[4]),5), min=0)
# updateNumericInput(session, "uppAsymptREF",
# value=round(as.numeric(Dat$coeffs_UN[5]),5), min=0)
# updateNumericInput(session, "uppAsymptTEST",
# value=round(as.numeric(Dat$coeffs_UN[6]),5), min=0)
# updateNumericInput(session, "slopeREF",
# value=round(as.numeric(Dat$coeffs_UN[1]),5))
# updateNumericInput(session, "slopeTEST",
# value=round(as.numeric(Dat$coeffs_UN[2]),5))
# updateNumericInput(session, "EC50",
# value=round(as.numeric(Dat$coeffs_UN[7]),5))
# updateNumericInput(session, "potDiff",
# value=round(as.numeric(Dat$coeffs_UN[7])- as.numeric(Dat$coeffs_UN[8]),5))
# }
# })
#
# observe({
# if(!is.null(Dat$dilution)) {
# updateNumericInput(session, "CONC1",
# value=as.numeric(Dat$dilution[1]))
# updateNumericInput(session, "CONC2",
# value=as.numeric(Dat$dilution[2]))
# updateNumericInput(session, "CONC3",
# value=as.numeric(Dat$dilution[3]))
# updateNumericInput(session, "CONC4",
# value=as.numeric(Dat$dilution[4]))
# updateNumericInput(session, "CONC5",
# value=as.numeric(Dat$dilution[5]))
# updateNumericInput(session, "CONC6",
# value=as.numeric(Dat$dilution[6]))
# updateNumericInput(session, "CONC7",
# value=as.numeric(Dat$dilution[7]))
# updateNumericInput(session, "CONC8",
# value=as.numeric(Dat$dilution[8]))
# updateNumericInput(session, "CONC9",
# value=as.numeric(Dat$dilution[9]))
# updateNumericInput(session, "CONC10",
# value=as.numeric(Dat$dilution[10]))
# updateNumericInput(session, "CONC11",
# value=as.numeric(Dat$dilution[11]))
# updateNumericInput(session, "CONC12",
# value=as.numeric(Dat$dilution[12]))
#
# }
# })
observe({
if(!is.null(Dat$MetaConc)) {
@@ -2119,33 +2214,33 @@ server <- function(input, output, session) {
####sim2 ----
sim2 <- reactive({
tab <- sim()
if (is.null(Dat$EXCEL)) return(tab) else return(Dat$EXCEL)
#if (is.null(Dat$EXCEL)) return(tab) else return(Dat$EXCEL)
})
#### Plot 4pl ----
output$plot <- renderPlot({
output$plot4plMeta <- renderPlot({
#browser()
sigmoid <- sigmoid()
det_sig=NULL
plot_f(sim2(),sigmoid, det_sig, TransFlag = F)
plot_f(sim2(), TransFlag = F)
})
#### Plot 4pl Transformed ----
output$plot4plTrans <- renderPlot({
output$plot4plTransMeta <- renderPlot({
#browser()
sigmoid <- sigmoid()
det_sig=NULL
plot_f(sim2(),sigmoid, det_sig, TransFlag = T)
plot_f(sim2(), TransFlag = T)
})
#### Testergebnisse für 4PL ----
observe({
if (is.null(sim2())) return(NULL)
if (is.null(input$PureErr4pl)) return(NULL)
if (is.null(input$PureErrMeta)) return(NULL)
#observeEvent(input$StartCalc,{
PureErrFlag <- input$PureErr4pl
PureErrFlag <- input$PureErrMeta
warning_text3 <- reactive({
ifelse(PureErrFlag, 'Pure error selected','')
})
@@ -2261,6 +2356,31 @@ server <- function(input, output, session) {
dom="t"
))
})
##### Concentrationtab Meta ----
output$ConctabMeta <- DT::renderDataTable({
if (!is.na(Dils()[1]) & is.na(Dils()[4])) return(NULL)
tab <- sim2()
if (is.character(tab)) stop(tab)
if (!is.na(Dils()[4])) {
noDilSer <- Dils()[4]
} else if (!is.null(Dat$noDilSeriesXL)) {
noDilSer <- Dat$noDilSeriesXL
} else { noDilSer <- 3 }
Conc <- CONC()
Conctab <- perConcTab(tab, noDilSeries = noDilSer)
Dat$Conctab <- Conctab
dat <- datatable(Conctab, options=list(
paging=T,
pageLength=12,
dom="t"
)) %>% formatStyle(0,
target='row',
backgroundColor = styleEqual(c("avs","sds","cv", "avs_test","sds_test","cv_test"),
c('lightgrey','lightgreen','pink','lightgrey','lightgreen','pink'))
) %>% formatRound(columns=colnames(Conctab), digits=3)
})
output$Conctab <- DT::renderDataTable({
if (!is.na(Dils()[1]) & is.na(Dils()[4])) return(NULL)
@@ -2287,10 +2407,10 @@ server <- function(input, output, session) {
) %>% formatRound(columns=colnames(Conctab), digits=3)
})
#### linear Plot output ----
#### process XL linearly, Plot output ----
output$plotLin <- renderPlot({
if (is.null(Dat$EXCEL)) return(NULL)
tab <- Dat$EXCEL
# tab <- sim2()
@@ -2336,70 +2456,25 @@ server <- function(input, output, session) {
Dat$circles <- circle
#browser()
mLin <- gsl_nls(readout ~ (intS+r)*isSample + intS*isRef + k*log_dose,
data=circle,
start=list(intS = 0, k=1,r=0),
control = gsl_nls_control(xtol=1e-10,ftol=1e-10,gtol=1e-10))
# alternativ: modAB <- lm(readout ~ log_dose+isSample, circle)
sum_mLin <- summary(mLin)
sigmoid <- Dat$coeffsMUnr
log_dose <- unique(all_l$log_dose)
seq_x <- seq(min(log_dose), max(log_dose),0.1)
SAMPLEtrue <- sigmoid[5] + (sigmoid[7]-sigmoid[5])/(1+exp(sigmoid[6]*((sigmoid[4]-sigmoid[8]-seq_x))))
REFtrue <- sigmoid[1] + (sigmoid[3]-sigmoid[1])/(1+exp(sigmoid[2]*((sigmoid[4]-seq_x))))
truePL_df <- cbind(seq_x,SAMPLEtrue, REFtrue)
p <- ggplot(all_l2,aes(x=log_dose,y=readout, color=factor(isRef))) +
geom_point() +
labs(title=paste("linear regression model", indS,indT), color="product") +
scale_colour_manual(labels = c("test","reference"), values=c("#C2173F","#4545BA")) +
ylim(min(all_l2$readout),max(all_l2$readout)) +
theme_bw()
p2 <- p + geom_line(data=pl_df,aes(x=lnC,y=plotS),color="#4545BA",
inherit.aes = F) +
geom_line(data=pl_df,aes(x=lnC,y=plotT),color="#C2173F",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="#C2173F", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="#4545BA", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("unrestricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
p3 <- p2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
# fit intercept for test and ref and common slope
pl_restS <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[2,1]*log_conc
pl_restT <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[3,1] + sum_mLin$coefficients[2,1]*log_conc
pl_rest <- data.frame(lnC=log_conc, plotS=pl_restS, plotT=pl_restT)
pr2 <- p + geom_line(data=pl_rest,aes(x=lnC,y=plotS),color="#4545BA",
inherit.aes = F) +
geom_line(data=pl_rest,aes(x=lnC,y=plotT),color="#C2173F",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="#C2173F", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="#4545BA", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("restricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
pr3 <- pr2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
grid.arrange(p3,pr3,nrow=1)
pLin <- PlotLinPLA_FUNC(circle, sigmoid = sigmoid, all_l2, pl_df, indS, indT)
pLin
})
output$plotLin2 <- renderPlot({
#### process metadata, Plot output ----
output$plotLinMeta <- renderPlot({
tab <- sim2()
if(is.null(tab)) return(NULL)
if (is.character(tab)) stop(tab)
#browser()
if (!is.na(Dils()[4])) noDilSer <- Dils()[4] else noDilSer = (ncol(tab)-1)/2
Conc <- CONC()
Conctab <- Dat$Conctab
log_conc <- log(Conc)
Conctab <- perConcTab(tab, noDilSer)
if (!is.na(Dils()[3])) noDil <- Dils()[3] else noDil = length(Conc)
slopeSt <- slopeTe <- matrix(NA, nrow=noDil-2,ncol=2)
@@ -2434,67 +2509,56 @@ server <- function(input, output, session) {
circleT <- all_mT[(indT*noDilSer-(noDilSer-1)):((indT+2)*noDilSer),]
circle <- rbind(circleS,circleT)
Dat$circles <- circle
Dat$circlesMeta <- circle
sigmoid <- sigmoid()
log_dose <- unique(all_l$log_dose)
seq_x <- seq(min(log_dose), max(log_dose),0.1)
SAMPLEtrue <- sigmoid[2] + (sigmoid[4]-sigmoid[2])/(1+exp(sigmoid[6]*((sigmoid[7]-log(input$potencydiff/100)-seq_x))))
REFtrue <- sigmoid[1] + (sigmoid[3]-sigmoid[1])/(1+exp(sigmoid[5]*((sigmoid[7]-seq_x))))
truePL_df <- cbind(seq_x,SAMPLEtrue, REFtrue)
p <- ggplot(all_l2,aes(x=log_dose,y=readout, color=factor(isRef))) +
geom_point() +
labs(title=paste("linear regression model", indS,indT), color="product") +
scale_colour_manual(labels = c("test","reference"), values=c("red","blue")) +
ylim(min(all_l2$readout),max(all_l2$readout)) +
theme_bw()
p2 <- p + geom_line(data=pl_df,aes(x=lnC,y=plotS),color="blue",
inherit.aes = F) +
geom_line(data=pl_df,aes(x=lnC,y=plotT),color="red",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="red", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="blue", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("unrestricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
p3 <- p2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
mLin <- gsl_nls(readout ~ (intS+r)*isSample + intS*isRef + k*log_dose,
data=circle,
start=list(intS = 0, k=1,r=0),
control = gsl_nls_control(xtol=1e-10,ftol=1e-10,gtol=1e-10))
# alternativ: modAB <- lm(readout ~ log_dose+isSample, circle)
sum_mLin <- summary(mLin)
pl_restS <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[2,1]*log_conc
pl_restT <- sum_mLin$coefficients[1,1] + sum_mLin$coefficients[3,1] + sum_mLin$coefficients[2,1]*log_conc
pl_rest <- data.frame(lnC=log_conc, plotS=pl_restS, plotT=pl_restT)
pr2 <- p + geom_line(data=pl_rest,aes(x=lnC,y=plotS),color="blue",
inherit.aes = F) +
geom_line(data=pl_rest,aes(x=lnC,y=plotT),color="red",
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=SAMPLEtrue),color="red", linetype=2,alpha=0.4,
inherit.aes = F) +
geom_line(data=data.frame(truePL_df),aes(x=seq_x,y=REFtrue),color="blue", linetype=2,alpha=0.4,
inherit.aes = F) +
labs(title = paste("restricted linear regression model",indS,indT), color="product") +
theme(legend.position="none", axis.text = element_text(size=14))
pr3 <- pr2 + geom_point(circle, mapping=aes(x=log_dose, y=readout, shape=factor(isRef),
size=5,alpha=0.2), inherit.aes = FALSE) +
scale_shape_manual(labels=c("test","reference"), values=c(21,21))
grid.arrange(p3,pr3,nrow=1)
#browser()
pLin2 <- PlotLinPLA_FUNC(circle, sigmoid = sigmoid, all_l2, pl_df,indS, indT)
pLin2
})
#### linear PLA tests ----
output$TESTSlin <- DT::renderDataTable({
#### linear PLA tests Metadata ----
output$TESTSlinMeta <- DT::renderDataTable({
tab <- sim2()
if (is.character(tab)) stop(tab)
if (is.null(tab)) return(NULL)
Conc <- CONC()
Limite <- Dat$limite
circlesMeta <- Dat$circlesMeta
PureErrFlag <- input$PureErrMeta
warning_text <- reactive({
ifelse(PureErrFlag, 'Pure error is selected','')
})
output$PureErrW <- renderText(warning_text())
browser()
LIN <- ANOVAlintests(tab,circlesMeta,Limite,PureErrFlag=PureErrFlag)
df <- LIN[[1]]
su_modU <- LIN[[2]]
su_mod2 <- LIN[[4]]
output$SummaryModABuMeta <- renderTable({ su_modU }, digits=5)
output$SummaryModABMeta <- renderTable({ su_mod2 }, digits=5)
slopeDiffCI <- t(data.frame(LIN[[3]]))
colnames(slopeDiffCI) <- c("slope difference","lower CI","upper CI")
output$SlopeDiffCIMeta <- renderTable({ slopeDiffCI },digits=5)
SelTestsL <- as.numeric(input$selectedSSTsLinear)
df2 <- df
Dat$ANOVAMeta <- df[,4:length(df)]
dat <- datatable(df2[,1:3],
options=list(
paging=T, dom="t",rownames=F
)) %>% formatStyle("test_results", target="row",backgroundColor = styleEqual(c(-1,0,1),
c("pink","lightgreen","lightgrey")))
})
#### linear PLA tests XLinput ----
output$TESTSlin <- DT::renderDataTable({
tab <- Dat$EXCEL
if (is.character(tab)) stop(tab)
Conc <- exp(tab$log_dose)
Limite <- list(as.numeric(input$lEACdiffla), as.numeric(input$uEACdiffla),
as.numeric(input$lEACratiola), as.numeric(input$uEACratiola),
as.numeric(input$lEACratioSlope), as.numeric(input$uEACratioSlope),
@@ -2502,14 +2566,49 @@ server <- function(input, output, session) {
as.numeric(input$lowerPot), as.numeric(input$upperPot),
as.numeric(input$lEACratioAdiff), as.numeric(input$uEACratioAdiff))
circles <- Dat$circles
noDil <- nrow(tab)
noDilSer <- Dat$noDilSeriesXL
Conctab <- perConcTab(tab, noDilSeries = noDilSer)
#browser()
slopeSt <- slopeTe <- matrix(NA, nrow=noDil-2,ncol=2)
for (i in 1:(noDil-2)) {
avs <- Conctab[noDilSer+1,]
threes <- data.frame(lnC=log(Conc[i:(i+2)]), resp=avs[i:(i+2)])
lm3St <- lm(resp ~ lnC, data=threes)
slopeSt[i,] <- lm3St$coefficients
avt <- Conctab[noDilSer*2+4,]
threet <- data.frame(lnC=log(Conc[i:(i+2)]), resp=avt[i:(i+2)])
lm3Te <- lm(resp ~ lnC, data=threet)
slopeTe[i,] <- lm3Te$coefficients
}
indS <- which(abs(slopeSt[,2]) == max(abs(slopeSt[,2])))
indT <- which(abs(slopeTe[,2]) == max(abs(slopeTe[,2])))
# pl_ <- slopeSt[indS,1]+slopeSt[indS,2]*log_conc
# pl_T <- slopeTe[indT,1]+slopeTe[indT,2]*log_conc
# pl_df <- data.frame(lnC=log_conc, plotS=pl_, plotT=pl_T)
all_l <- melt(data.frame(tab), id.vars="log_dose",variable.name="replname",value.name="readout")
isRef <- rep(c(1,0), 1,each=nrow(all_l)/2)
isSample <- rep(c(0,1), 1,each=nrow(all_l)/2)
all_l2 <- cbind(all_l,isRef, isSample)
all_l2S <- all_l2[all_l2$isRef == 1,]
all_l2T <- all_l2[all_l2$isRef == 0,]
all_mS <- all_l2S[order(all_l2S$log_dose, decreasing=TRUE),]
all_mT <- all_l2T[order(all_l2T$log_dose, decreasing=TRUE),]
circleS <- all_mS[(indS*noDilSer-(noDilSer-1)):((indS+2)*noDilSer),]
circleT <- all_mT[(indT*noDilSer-(noDilSer-1)):((indT+2)*noDilSer),]
circle <- rbind(circleS,circleT)
PureErrFlag <- input$PureErr
warning_text <- reactive({
ifelse(PureErrFlag, 'Pure error is selected','')
})
output$PureErrW <- renderText(warning_text())
LIN <- ANOVAlintests(tab,circles,Limite,PureErrFlag=PureErrFlag)
output$PureErrW3 <- renderText(warning_text())
#browser()
LIN <- ANOVAlintests(tab,circle,Limite,PureErrFlag=PureErrFlag)
df <- LIN[[1]]
su_modU <- LIN[[2]]
su_mod2 <- LIN[[4]]
@@ -2533,7 +2632,7 @@ server <- function(input, output, session) {
})
#### output 4PL ANOVA tests ---
#### output 4PL ANOVA tests Meta ----
output$ANOVA <- DT::renderDataTable({
sigmoid <- sigmoid()
tab <- ANOVA4plUnresfunc(sim2()) # ,sigmoid
@@ -2545,18 +2644,33 @@ server <- function(input, output, session) {
c("lightgrey")))
})
#### output 4PL ANOVA tests XL ----
# not needed
# output$ANOVA_XL <- DT::renderDataTable({
# tab <- Dat$EXCEL
# tab <- ANOVA4plUnresfunc(sim2()) # ,sigmoid
# dat <- datatable(tab,
# options=list(
# dom="t",rownames=F
# )) %>% formatStyle("p_value", target="row",
# backgroundColor = styleEqual(c("p_value"),
# c("lightgrey")))
# })
#### output RMSEs ----
output$RMSE <- renderText({
paste("RMSE (unrestricted model):", Dat$RMSE_unr, "(~ entered % upper-lower asymptote)\n",
"RMSE restricted model:", Dat$RMSE_r, "\n",
"Pure RMSE unrestricted model:", Dat$RMSE_pure, "\n",
"%SD (unr model): ", Dat$RMSE_unr*100/Dat$up_lowAs, "(calculated as: RMSE/(upper-lower Asymptote)*100\n",
paste("RMSE (unrestricted model):", Dat$RMSE_unr, "(Use it to compare against RMSE restr. model for non-parallelism)\n",
"RMSE (restricted model):", Dat$RMSE_r, "\n",
"Pure RMSE (unrestricted model):", Dat$RMSE_pure, "\n",
"%SD (unr. model): ", Dat$RMSE_unr*100/Dat$up_lowAs, "(calculated as: RMSE/(upper-lower Asymptote)*100\n",
"RMSE (log restr. model): ", Dat$RMSE_Rlog, "\n",
"RMSE (log unrestr. model): ", Dat$RMSE_Ulog, "\n",
"%SDlog (unr model): ", Dat$RMSE_Ulog*100/Dat$up_lowAslog )
})
output$ANOVAlin <- DT::renderDataTable({
if (is.null(Dat$ANOVA)) return(NULL)
ANOVAlin <- Dat$ANOVA
dat <- datatable(ANOVAlin,
options=list(
@@ -2565,9 +2679,19 @@ server <- function(input, output, session) {
backgroundColor = styleEqual(c("p.value"),
c("lightgrey")))
})
### output pot tab ----
output$ANOVAlinMeta <- DT::renderDataTable({
ANOVAlin <- Dat$ANOVAMeta
dat <- datatable(ANOVAlin,
options=list(
dom="t",rownames=F
)) %>% formatStyle("p.value", target='cell',
backgroundColor = styleEqual(c("p.value"),
c("lightgrey")))
})
#### output Lin pot tab XL ----
output$pottab <- DT::renderDataTable({
if (is.null(Dat$circles)) return(NULL)
Lim <- list(as.numeric(input$lEACdiffla), as.numeric(input$uEACdiffla),
as.numeric(input$lEACratiola), as.numeric(input$uEACratiola),
as.numeric(input$lEACratioSlope), as.numeric(input$uEACratioSlope),
@@ -2582,17 +2706,38 @@ server <- function(input, output, session) {
options=list(
dom="t",rownames=F
)) %>% formatStyle("test_result", target='row',
backgroundColor = styleEqual(c(0,1), c("lightgrey")))
backgroundColor = styleEqual(c(0,1), c("lightgrey","#F9545488")))
})
#### 4pl potency table ----
### output pot tab Meta ----
output$pottabMeta <- DT::renderDataTable({
Lim <- list(as.numeric(input$lEACdiffla), as.numeric(input$uEACdiffla),
as.numeric(input$lEACratiola), as.numeric(input$uEACratiola),
as.numeric(input$lEACratioSlope), as.numeric(input$uEACratioSlope),
as.numeric(input$lEACratioua), as.numeric(input$uEACratioua),
as.numeric(input$lowerPot), as.numeric(input$upperPot))
circles <- Dat$circlesMeta
PureErrFlag <- input$PureErrMeta
pottab <- LinPotTab(circles,Lim,PureErrFlag = PureErrFlag)
#browser()
dat <- datatable(pottab,
options=list(
dom="t",rownames=F
)) %>% formatStyle("test_result", target='row',
backgroundColor = styleEqual(c(0,1), c("lightgrey","#F9545488")))
})
#### 4pl potency table Meta ----
observe({
#browser()
if (is.null(sim2()) | is.null(Dils())) return(NULL)
ro_new <- sim2()
Dils_ <- Dils()
if (!is.na(Dils()[4])) noDilSer <- Dils()[4] else noDilSer <- 3
PureErrFl <- input$PureErr4pl
PureErrFl <- input$PureErrMeta
pottab4 <- pot4plFUNC(ro_new = ro_new, PureErrFlag = PureErrFl)
#browser()
Lim <- list(as.numeric(input$lEACdiffla), as.numeric(input$uEACdiffla),
@@ -2640,6 +2785,62 @@ server <- function(input, output, session) {
})
})
#### 4pl potency table XL ----
observe({
#browser()
if (is.null(Dat$EXCEL)) return(NULL)
ro_new <- Dat$EXCEL
noDilSer <- Dat$noDilSeriesXL
PureErrFl <- input$PureErr
pottab4 <- pot4plFUNC(ro_new = ro_new, PureErrFlag = PureErrFl)
#browser()
Lim <- list(as.numeric(input$lEACdiffla), as.numeric(input$uEACdiffla),
as.numeric(input$lEACratiola), as.numeric(input$uEACratiola),
as.numeric(input$lEACratioSlope), as.numeric(input$uEACratioSlope),
as.numeric(input$lEACratioua), as.numeric(input$uEACratioua),
as.numeric(input$lowerPot), as.numeric(input$upperPot))
pottab4_ <- data.frame(pottab4)
pottab4_$potency <- round(as.numeric(pottab4[,2])*100,1)
pottab4_$`lower95%CI` <- round(as.numeric(pottab4[,3])*100,2)
pottab4_$`upper95%CI` <- round(as.numeric(pottab4[,4])*100,2)
pottab4_$relative_lowerCL <- round(pottab4_[,6]/pottab4_[,5]*100,2)
pottab4_$relative_upperCL <- round(pottab4_[,7]/pottab4_[,5]*100,2)
if (as.numeric(pottab4_$relative_lowerCL[1]) > Lim[[9]] & as.numeric(pottab4_$relative_upperCL[1]) < Lim[[10]] ) {
test_potCI <- 0
} else {test_potCI <- 1 }
if (as.numeric(pottab4_$relative_lowerCL[2]) > Lim[[9]] & as.numeric(pottab4_$relative_upperCL[2]) < Lim[[10]] ) {
test_potUCI <- 0
} else {test_potUCI <- 1 }
if (as.numeric(pottab4_$relative_lowerCL[3]) > Lim[[9]] & as.numeric(pottab4_$relative_upperCL[3]) < Lim[[10]] ) {
test_potCI_t <- 0
} else {test_potCI_t <- 1 }
if (as.numeric(pottab4_$relative_lowerCL[4]) > Lim[[9]] & as.numeric(pottab4_$relative_upperCL[4]) < Lim[[10]] ) {
test_potUCI_t <- 0
} else {test_potUCI_t <- 1 }
pottab4_ <- cbind(pottab4_[,-(2:4)], data.frame(tests=c(test_potCI, test_potUCI,test_potCI_t,test_potUCI_t)))
colnames(pottab4_) <- c("model","potency","lower95%CI","upper95%CI","relative_lower95%CI","relative_upper95%CI","test_result")
output$pottab4plXL <- DT::renderDataTable({
dat <- datatable(pottab4_[1:2,],
options=list(digits=3,
paging=T, dom="t",rownames=F
)) %>% formatStyle("test_result", target="row",backgroundColor = styleEqual(c(0,1),
c("#B5C74055","#F9545455")))
})
output$pottab4plTransXL <- DT::renderDataTable({
dat <- datatable(pottab4_[3:4,],
options=list(digits=3,
paging=T, dom="t",rownames=F
)) %>% formatStyle("test_result", target="row",backgroundColor = styleEqual(c(0,1),
c("#B5C74055","#F9545455")))
})
})
#### Dilutions Simulator ----
output$plotfordilutions <- renderPlot({
tab <- sim2()
@@ -2686,7 +2887,7 @@ server <- function(input, output, session) {
Xbend200u <- sigmoid[7] - 0.693147+1.5434/sigmoid[5]
Xbend50 <- max(Xbend50l, Xbend50u)
Xbend200 <- min(Xbend200l, Xbend200u)
dummy <- plot_f(tab,sigmoid,det_sig=NULL)
dummy <- plot_f(tab)
} else {
#browser()
@@ -2698,7 +2899,7 @@ server <- function(input, output, session) {
Xbend200u <- det_sig[7] - 0.693147+1.5434/det_sig[1]
Xbend50 <- max(Xbend50l, Xbend50u)
Xbend200 <- min(Xbend200l, Xbend200u)
dummy <- plot_f(tab,sigmoid=NULL,det_sig=det_sig)
dummy <- plot_f(tab)
}