Last updated: 2025-03-28

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File Version Author Date Message
Rmd 935a46e Shashikant Koul 2025-03-28 Fix patient order based on on-treatment dates
html 935a46e Shashikant Koul 2025-03-28 Fix patient order based on on-treatment dates
Rmd 9bbcb47 Shashikant Koul 2025-03-27 Initial commit
html 9bbcb47 Shashikant Koul 2025-03-27 Initial commit

Patients are listed along vertical axis, separated into those that are evaluable by ARTEMIS-DELFI method at the follow up timepoint. Baseline ARTEMIS-DELFI score is plotted on the left side of the plot, with follow-up ARTEMIS-DELFI score on the right side of the plot. BOR RECIST 1.1 is shown, separated by color, in central panel.

library(tidyverse)
library(readxl)
library(here)
source(here("code/utility_funcs.R"))
#----------------------------------------------------------------------------------
# Prepare the data
#----------------------------------------------------------------------------------
# Delfi scores
delfi_scr <- read_csv(here("data/artemis.csv")) %>% 
    left_join(read_excel(here("data/checkpac_plasma_manifest.xlsx"), col_type=c("text", "text", "text")) %>% 
    select(cgid = `Sample ID*`, patient_id = Patient, date_blood_draw = Date),
    by = join_by(id == cgid)) %>%
    select(patient_id, date_blood_draw, ARTEMIS_single_DELFI_SSLs_Ensemble) %>%
    drop_na() %>%
    mutate(date_blood_draw = as.Date(as.numeric(date_blood_draw), origin="1899-12-30"))
Rows: 217 Columns: 4
── Column specification ────────────────────────────────────────────────────────
Delimiter: ","
chr (1): id
dbl (3): ARTEMIS_single_DELFI_SSLs_Ensemble, ARTEMIS_Ensemble, ARTEMIS_Mathi...

ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
# Best RECIST response
best_resp <- read_excel(here("data/CheckPAC_clinical_annotated011622.xlsx")) %>%
             select(subject_id = StudySubjectID,
                    bor = `Best overall confirmed response (RECIST)`) %>%
             inner_join(read_excel(here("data/ID_comparison.xlsx")) %>%
                    filter(!unlist(lapply(CGID, function(x) any(str_detect(x, c("CGPLPA225", "CGPLPA783", "CGPLPA795")))))) %>%
                    select(patient_id = CGID, subject_id = StudySubjectID) %>%
                    mutate(patient_id = substring(patient_id, 1, 9))) %>%
             mutate(bor = ifelse(bor == "Not evaluable", "NE", bor)) 
Joining with `by = join_by(subject_id)`
# Baseline and on-treatment blood draw dates
#blot_date <- read_csv(here("data/checkpac_baseline_endpoint_dates.csv"))
blot_date <- read_csv(here("data/checkpac_baseline_p2_dates.csv")) %>%
    mutate(tx_start_date = as.Date(tx_start_date, "%m/%d/%y"),
           ct_flwup_date = as.Date(ct_flwup_date, "%m/%d/%y"),
           baseline = as.Date(baseline, "%m/%d/%y"),
           endpoint = as.Date(endpoint, "%m/%d/%y"),
           `week 2` = as.Date(`week 2`, "%m/%d/%y"))
Rows: 40 Columns: 7
── Column specification ────────────────────────────────────────────────────────
Delimiter: ","
chr (6): patient_id, tx_start_date, ct_flwup_date, baseline, endpoint, week 2
lgl (1): ct_flwup

ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
#----------------------------------------------------------------------------------
# Patient selection for analysis
#----------------------------------------------------------------------------------
# (1) Patients with on-treatment Delfi score are kept in the analysis
anlys_pat <- pull(drop_na(blot_date, endpoint), patient_id)
lefto_pat <- setdiff(pull(blot_date, patient_id), anlys_pat)

# (2) Order patients based on baseline Delfi scores and on-treatment if baseline is NA 
order_bas <- delfi_scr %>%
             inner_join(blot_date %>% 
             select(patient_id, date_blood_draw=baseline) %>%
             drop_na()) %>%
             arrange(ARTEMIS_single_DELFI_SSLs_Ensemble) %>%
             pull(patient_id)
Joining with `by = join_by(patient_id, date_blood_draw)`
order_ont <- delfi_scr %>%
             inner_join(blot_date %>% 
             select(patient_id, date_blood_draw=endpoint) %>%
             drop_na()) %>%
             arrange(desc(ARTEMIS_single_DELFI_SSLs_Ensemble)) %>%
             pull(patient_id)
Joining with `by = join_by(patient_id, date_blood_draw)`
# (3) Add the remaining patients without tumor mutations information         
order_std <- c(setdiff(lefto_pat, order_ont),   # patients without baseline or on-treatment score
               intersect(order_ont, lefto_pat), # patients with baseline, but no on-treatment score
               intersect(order_bas, setdiff(anlys_pat, order_ont)), # patients with no baseline, but on-treatment score
               intersect(order_ont, anlys_pat)) # patients with both baseline and on-treatment score

# (4) Split the order into two groups
anlys_ord <- unlist(lapply(order_std, function(x) if(x %in% anlys_pat) x))
lefto_ord <- unlist(lapply(order_std, function(x) if(x %in% lefto_pat) x))

#----------------------------------------------------------------------------------
# Split the delfi score into baseline and on-treatment
#----------------------------------------------------------------------------------
delfi_scr_basl <- inner_join(delfi_scr, rename(drop_na(blot_date, baseline), date_blood_draw=baseline))
Joining with `by = join_by(patient_id, date_blood_draw)`
delfi_scr_ontr <- inner_join(delfi_scr, rename(drop_na(blot_date, endpoint), date_blood_draw=endpoint))
Joining with `by = join_by(patient_id, date_blood_draw)`
#----------------------------------------------------------------------------------
# Split the data into patients analyzed and left out 
#----------------------------------------------------------------------------------
## Delfi score 
### Baseline
delfi_scr_bsl1 <- left_join(tibble(patient_id = anlys_ord), delfi_scr_basl)
Joining with `by = join_by(patient_id)`
delfi_scr_bsl2 <- left_join(tibble(patient_id = lefto_ord), delfi_scr_basl)
Joining with `by = join_by(patient_id)`
### On-treatment
delfi_scr_ont1 <- left_join(tibble(patient_id = anlys_ord), delfi_scr_ontr)
Joining with `by = join_by(patient_id)`
delfi_scr_ont2 <- left_join(tibble(patient_id = lefto_ord), delfi_scr_ontr)
Joining with `by = join_by(patient_id)`
## Cellularity
bins <- seq(0,1,0.2); bins[length(bins)] <- bins[length(bins)]+1e-6

## Best response
best_resp_all1 <- left_join(tibble(patient_id = anlys_ord), best_resp)
Joining with `by = join_by(patient_id)`
best_resp_all2 <- left_join(tibble(patient_id = lefto_ord), best_resp)
Joining with `by = join_by(patient_id)`
#----------------------------------------------------------------------------------
# Plotting presets
#----------------------------------------------------------------------------------
## Panel widths
w1 <- 3; w2 <- 17; w5 <- 2; w6 <- 17

## Panel heights
h1 <- 33-1    # analyzed samples
#h2 <- 7-1   # left out samples
h2 <- 7.5

## Panel margins
tp <- 5     # top margin
bt <- 2     # bottom margin
r12 <- 1/3 #h2/h1

## Y-axis extension
yex <- 2

## Fix the layout
lay.mat <- layout.matrix(c(h1,h2), c(w1,w2,w5,w6))
layout(lay.mat)
par(oma=c(1,0,0,0)) # Thin outer margins

# Text size
xaxis.cex <- 0.7
xaxis.spine.cex <- 0.6 

## Best response
resp_palette <- c("green", "darkgoldenrod1", "red", "grey") 
names(resp_palette) <- c("PR", "SD", "PD", "NE")
best_resp_col1 <- resp_palette[best_resp_all1$bor]
best_resp_col2 <- resp_palette[best_resp_all2$bor]

#----------------------------------------------------------------------------------
# Empty plot
#----------------------------------------------------------------------------------
## ANALYZED panel
par(mar=c(bt,0,tp,2))
# Make the horizontal bars for tumor mutations
ytick1 <- barplot(rep(NA, length(anlys_ord)), horiz=TRUE, axes=FALSE, width=0.8, space=0.25,
                  ylim=c(0.6-yex, length(anlys_ord)-0.4+yex),
                  xlim=c(-10,0),
                  col=NA, border=NA,
                  yaxs="i")

# Adding y-axis on the right
axis(4, at=ytick1, labels=anlys_ord, line=-0.5, las=2, lwd=0, font=1)

## LEFT OUT panel
par(mar=c(r12*bt,0,r12*tp,2))
# Make the horizontal bars for tumor mutations
ytick2 <- barplot(rep(NA, length(lefto_ord)), horiz=TRUE, axes=FALSE, width=0.8, space=0.25,
                  ylim=c(0.6-r12*yex, length(lefto_ord)-0.4+r12*yex),
                  xlim=c(-10,0),
                  col=NA, border=NA,
                  yaxs="i")

# Adding y-axis on the right
axis(4, at=ytick2, labels=lefto_ord, line=-0.5, las=2, lwd=0, font=1)

#-----------------------------------------------------------
# Baseline MAF
#----------------------------------------------------------------------------------
breaks <- pretty(c(delfi_scr_basl$ARTEMIS_single_DELFI_SSLs_Ensemble, delfi_scr_ontr$ARTEMIS_single_DELFI_SSLs_Ensemble))

## ANALYZED panel
par(mar=c(bt,4,tp,0))
# Make the lollipop plot
# Empty plot - draw the points on top of sticks
plot(x = -delfi_scr_bsl1$ARTEMIS_single_DELFI_SSLs_Ensemble, y = c(1:nrow(delfi_scr_bsl1)), bty="n", axes=FALSE,
     xlab = "", ylab = "", pch = NA, xlim = sort(-range(breaks)), cex=2,
     ylim = c(1-yex, nrow(delfi_scr_bsl1)+yex),
     yaxs="i")
# Draw the sticks
sapply(1:nrow(delfi_scr_bsl1), function(i) {
     lines(c(-delfi_scr_bsl1$ARTEMIS_single_DELFI_SSLs_Ensemble[c(1:nrow(delfi_scr_bsl1)) == i], 0), c(i,i),
           col="grey", lwd=2)})
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# Draw the heads
points(x=-delfi_scr_bsl1$ARTEMIS_single_DELFI_SSLs_Ensemble, y=1:nrow(delfi_scr_bsl1), pch=16)

# Draw y-axis using abline
abline(v=0, lwd=1)

# Draw x-axis at the top
axis(3, at=-breaks, labels=breaks, lwd=1, font=1)
mtext("Baseline Artemis-DELFI score", 3, cex=xaxis.cex, line=2.5)

## LEFT OUT panel
par(mar=c(r12*bt,4,r12*tp,0))
# Make the lollipop plot
# Empty plot - draw the points on top of sticks
plot(x = delfi_scr_bsl2$ARTEMIS_single_DELFI_SSLs_Ensemble, y = c(1:nrow(delfi_scr_bsl2)), bty="n", axes=FALSE,
     xlab = "", ylab = "", pch = NA, xlim = sort(-range(breaks)), cex=2,
     ylim = c(1-r12*yex, nrow(delfi_scr_bsl2)+r12*yex),
     yaxs="i")
# Draw the sticks
sapply(1:nrow(delfi_scr_bsl2), function(i) {
     lines(c(-delfi_scr_bsl2$ARTEMIS_single_DELFI_SSLs_Ensemble[c(1:nrow(delfi_scr_bsl2)) == i], 0), c(i,i),
           col="grey", lwd=2)})
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# Draw the heads
points(x=-delfi_scr_bsl2$ARTEMIS_single_DELFI_SSLs_Ensemble, y=1:nrow(delfi_scr_bsl2), pch=16)

# Draw y-axis using abline
abline(v=0, lwd=1)

# Draw x-axis at the top
#axis(3, at=-breaks, labels=breaks, lwd=1, font=1)
#mtext("Baseline DELFI score", 3, cex=xaxis.cex, line=2.5)


#----------------------------------------------------------------------------------
# Best RECIST response
#----------------------------------------------------------------------------------
## ANALYZED panel
par(mar=c(bt,0,tp,0))
plot(x=rep(0, nrow(best_resp_all1)), y=1:nrow(best_resp_all1),
     pch=22, col="grey", bg=best_resp_col1,
     bty="n", axes=FALSE, xlab="", ylab="", cex=2, font=1,
     ylim = c(1-yex, nrow(best_resp_all1)+yex),
     yaxs="i")
mtext("BOR\nRECIST", 3, las=2, cex=xaxis.spine.cex)

## LEFT OUT panel 
par(mar=c(r12*bt,0,r12*tp,0))
plot(x=rep(0, nrow(best_resp_all2)), y=1:nrow(best_resp_all2),
     pch=22, col="grey", bg=best_resp_col2,
     bty="n", axes=FALSE, xlab="", ylab="", cex=2, font=1,
     ylim = c(1-r12*yex, nrow(best_resp_all2)+r12*yex),
     yaxs="i")
#mtext("BOR\nRECIST", 3, las=2, cex=xaxis.spine.cex)

#----------------------------------------------------------------------------------
# On-treatment MAF
#----------------------------------------------------------------------------------
breaks <- pretty(c(delfi_scr_basl$ARTEMIS_single_DELFI_SSLs_Ensemble, delfi_scr_ontr$ARTEMIS_single_DELFI_SSLs_Ensemble))

## ANALYZED panel
par(mar=c(bt,0,tp,4))
# Make the lollipop plot
# Empty plot - draw the points on top of sticks
plot(x = delfi_scr_ont1$ARTEMIS_single_DELFI_SSLs_Ensemble, y = c(1:nrow(delfi_scr_ont1)), bty="n", axes=FALSE,
     xlab = "", ylab = "", pch = NA, xlim = range(breaks), cex=2,
     ylim = c(1-yex, nrow(delfi_scr_ont1)+yex),
     yaxs="i")
# Draw the sticks
sapply(1:nrow(delfi_scr_ont1), function(i) {
     lines(c(0,delfi_scr_ont1$ARTEMIS_single_DELFI_SSLs_Ensemble[c(1:nrow(delfi_scr_ont1)) == i]), c(i,i),
           col="grey", lwd=2)})
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# Draw the heads
points(x=delfi_scr_ont1$ARTEMIS_single_DELFI_SSLs_Ensemble, y=1:nrow(delfi_scr_ont1), pch=16)

# Draw y-axis using abline
abline(v=0, lwd=1)

# Draw x-axis at the top
axis(3, at=breaks, labels=breaks, lwd=1, font=1)
mtext("On-treatment Artemis-DELFI score", 3, cex=xaxis.cex, line=2.5)

## LEFT OUT panel
par(mar=c(r12*bt,0,r12*tp,4))
# Make the lollipop plot
# Empty plot - draw the points on top of sticks
plot(x = delfi_scr_ont2$ARTEMIS_single_DELFI_SSLs_Ensemble, y = c(1:nrow(delfi_scr_ont2)), bty="n", axes=FALSE,
     xlab = "", ylab = "", pch = NA, xlim = range(breaks), cex=2,
     ylim = c(1-r12*yex, nrow(delfi_scr_ont2)+r12*yex),
     yaxs="i")
# Draw the sticks
sapply(1:nrow(delfi_scr_ont2), function(i) {
     lines(c(0,delfi_scr_ont2$ARTEMIS_single_DELFI_SSLs_Ensemble[c(1:nrow(delfi_scr_ont2)) == i]), c(i,i),
           col="grey", lwd=2)})
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# Draw the heads
points(x=delfi_scr_ont2$ARTEMIS_single_DELFI_SSLs_Ensemble, y=1:nrow(delfi_scr_ont2), pch=16)

# Draw y-axis using abline
abline(v=0, lwd=1)

#----------------------------------------------------------------------------------
# Adding floating legend for BOR 
#----------------------------------------------------------------------------------
add.legend(title="BOR RECIST", x=0.65, y=6, xadj=0.022, 
           labels=names(resp_palette), col_palette=resp_palette, border="grey")

#----------------------------------------------------------------------------------

# Draw x-axis at the top
#axis(3, at=breaks, labels=breaks, lwd=1, font=1)
#mtext("On-treatment DELFI score", 3, cex=xaxis.cex, line=2.5)

#----------------------------------------------------------------------------------
# Annotations
#----------------------------------------------------------------------------------
par(fig=c(0,1,0,1), mar=c(0,1,0,1), new=TRUE)

# Samples that were dropped from the analysis, because of missing data
plot(c(-10,10), 15*c(1,1), col=NA, axes=FALSE, xpd=TRUE)
text(0.63,11.00, "Not evaluable \n(Missing on-treatment blood draw)", adj=0.5)
draw.bracket(0.75,10.60,-10.5,10)

Version Author Date
935a46e Shashikant Koul 2025-03-28
9bbcb47 Shashikant Koul 2025-03-27
#----------------------------------------------------------------------------------

sessionInfo()
R version 4.4.1 (2024-06-14)
Platform: aarch64-apple-darwin20
Running under: macOS 15.3.1

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRblas.0.dylib 
LAPACK: /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.0

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

time zone: America/New_York
tzcode source: internal

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] here_1.0.1      readxl_1.4.5    lubridate_1.9.4 forcats_1.0.0  
 [5] stringr_1.5.1   dplyr_1.1.4     purrr_1.0.4     readr_2.1.5    
 [9] tidyr_1.3.1     tibble_3.2.1    ggplot2_3.5.1   tidyverse_2.0.0
[13] workflowr_1.7.1

loaded via a namespace (and not attached):
 [1] sass_0.4.9        generics_0.1.3    stringi_1.8.4     hms_1.1.3        
 [5] digest_0.6.37     magrittr_2.0.3    timechange_0.3.0  evaluate_1.0.3   
 [9] grid_4.4.1        fastmap_1.2.0     cellranger_1.1.0  rprojroot_2.0.4  
[13] jsonlite_1.9.1    processx_3.8.6    whisker_0.4.1     ps_1.9.0         
[17] promises_1.3.2    httr_1.4.7        scales_1.3.0      jquerylib_0.1.4  
[21] cli_3.6.4         crayon_1.5.3      rlang_1.1.5       bit64_4.6.0-1    
[25] munsell_0.5.1     withr_3.0.2       cachem_1.1.0      yaml_2.3.10      
[29] parallel_4.4.1    tools_4.4.1       tzdb_0.4.0        colorspace_2.1-1 
[33] httpuv_1.6.15     vctrs_0.6.5       R6_2.6.1          lifecycle_1.0.4  
[37] git2r_0.35.0      bit_4.6.0         fs_1.6.5          vroom_1.6.5      
[41] pkgconfig_2.0.3   callr_3.7.6       pillar_1.10.1     bslib_0.9.0      
[45] later_1.4.1       gtable_0.3.6      glue_1.8.0        Rcpp_1.0.14      
[49] xfun_0.51         tidyselect_1.2.1  rstudioapi_0.17.1 knitr_1.49       
[53] htmltools_0.5.8.1 rmarkdown_2.29    compiler_4.4.1    getPass_0.2-4