Last updated: 2023-06-16

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Knit directory: Cardiotoxicity/

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library(car)
#library(dr4pl) no longer used
library(tidyverse)
library(tinytex)
library(BiocGenerics)
library(data.table)
library(drc)
# library(Hmisc)
library(cowplot)
# library(grid)
library(ggsignif)
library(RColorBrewer)
library(broom)

Figure 1

Top2i drugs affect cardiomyocyte viability in a dose dependent manner.

A. Project Overview

things to note about this image so far: Need to import into illustrator. Goal is to have colors changes on Drugs from sick purple and jaundice yellow, to a red tone and a blue tone for non-ACs. I also want to change to add a time line of treatment.

B. Example Dose response curves from 48 hour drug exposure.

daplot <- readRDS("output/daplot.RDS")  
dxplot <- readRDS("output/dxplot.RDS")
epplot<- readRDS("output/epplot.RDS")
mtplot<- readRDS("output/mtplot.RDS")
trplot<- readRDS("output/trplot.RDS")
veplot<- readRDS("output/veplot.RDS")

plan2 <-  cowplot::plot_grid(daplot,dxplot,epplot,mtplot, trplot,veplot,ncol =3)
print(plan2)

Lines are a log-logistic regression of the mean from quadruplicates at 8 separate concentrations for each condition, except (trastuzmab)TRZ, which is 7 concentrations.

C. 48 hour 50% lethal dose plot

drug_palc <- c("#8B006D","#DF707E","#F1B72B", "#3386DD","#707031","#41B333")
BC_cell_lines <- read.csv("data/BC_cell_lines.csv",row.names = 1)
avgLD50 <- readRDS("data/avgLD50.RDS")
  
graphLD50 <- 
  avgLD50 %>%     
  mutate(Treatment = case_match (Treatment, "Daun"~"Daunorubicin",  
                                 "Doxo"~"Doxorubicin",
                                 "Epi"~"Epirubicin",
                                 "Mito"~"Mitoxantrone",
                                 "Tras"~"Trastuzumab",
                                 "Veh"~ "Vehicle", 
                                 .default= Treatment)) %>%
  mutate(indv= factor(indv)) %>%
  ggplot(., (aes(x = (Treatment), y = log10(LD50)))) +
  geom_boxplot(position = "identity", aes(fill=Treatment))+
  geom_point(aes(color = indv,
                 size = 5,alpha = 0.5)) +
  ggtitle(expression("Experimentally-derived LD"[50]*"s from treated cardiomyocytes"))+
  xlab("Treatment")+
  ylab(bquote('Log'[10]~ 'LD'[50]~'in '*mu*M))+
  scale_color_brewer(palette = "Dark2",
                     name = "Individual", 
                     labels = c("1","2","3","4","5","6"))+
  ylim(-2,2)+
  scale_fill_manual(values=drug_palc)+
  theme_bw() + 
  theme(plot.title = element_text(hjust =0.5, size = 18))+
        guides(alpha ="none", size = "none")+
  #theme(strip.background = element_rect(fill = "transparent")) +
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        # legend.position = "none",
        axis.title = element_text(size = 15, color = "black"),
        axis.ticks = element_line(linewidth = 1.5),
        axis.line = element_line(linewidth = 1.5),
        axis.text = element_text(size = 12, color = "black", angle = 0),
        strip.text.x = element_text(size = 15, color = "black", face = "bold"))   

graphLD50

## D. Breast Cancer cell line 50% lethal dose plot

graphBC <- BC_cell_lines %>%
    mutate(Cell_line= factor(Cell_line)) %>% 
  pivot_longer(.,col=!Cell_line,names_to = 'Treatment',values_to = 'LD50') %>% 
  ggplot(., (aes(x = (Treatment), y = log10(LD50)))) +
  geom_boxplot(position = "identity",aes(fill=Treatment))+
  geom_point(aes(color = Cell_line,
                 size = 5,alpha = 0.5)) +
  ggtitle(expression("Breast cancer cell line reported  LD"[50]*"s"))+
  xlab("")+
  ylab(bquote('Log'[10]~ 'LD'[50]~'in '*mu*M))+
  scale_color_brewer(palette = "Spectral",
                     name = "Cell lines")+
          scale_fill_manual(values=drug_palc)+
  ylim(-2,2)+
  theme_bw() + 
  theme(plot.title = element_text(hjust =0.5, size = 18))+
  guides(alpha ="none", size = "none", fill= "none")+
  #theme(strip.background = element_rect(fill = "transparent")) +
  theme(plot.title = element_text(size = rel(1.5), hjust = 0.5),
        # legend.position = "none",
         axis.title = element_text(size = 15, color = "black"),
        axis.ticks = element_line(linewidth = 1.5),
        axis.line = element_line(linewidth = 1.5),
        axis.text = element_text(size = 12, color = "black", angle = 0),
        strip.text.x = element_text(size = 15, color = "black", face = "bold"))   
  graphBC


sessionInfo()
R version 4.2.2 (2022-10-31 ucrt)
Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 10 x64 (build 19045)

Matrix products: default

locale:
[1] LC_COLLATE=English_United States.utf8 
[2] LC_CTYPE=English_United States.utf8   
[3] LC_MONETARY=English_United States.utf8
[4] LC_NUMERIC=C                          
[5] LC_TIME=English_United States.utf8    

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

other attached packages:
 [1] broom_1.0.5         RColorBrewer_1.1-3  ggsignif_0.6.4     
 [4] cowplot_1.1.1       drc_3.0-1           MASS_7.3-60        
 [7] data.table_1.14.8   BiocGenerics_0.42.0 tinytex_0.45       
[10] lubridate_1.9.2     forcats_1.0.0       stringr_1.5.0      
[13] dplyr_1.1.2         purrr_1.0.1         readr_2.1.4        
[16] tidyr_1.3.0         tibble_3.2.1        ggplot2_3.4.2      
[19] tidyverse_2.0.0     car_3.1-2           carData_3.0-5      
[22] workflowr_1.7.0    

loaded via a namespace (and not attached):
 [1] httr_1.4.6       sass_0.4.6       jsonlite_1.8.5   splines_4.2.2   
 [5] gtools_3.9.4     bslib_0.5.0      getPass_0.2-2    highr_0.10      
 [9] yaml_2.3.7       pillar_1.9.0     backports_1.4.1  lattice_0.21-8  
[13] glue_1.6.2       digest_0.6.31    promises_1.2.0.1 colorspace_2.1-0
[17] sandwich_3.0-2   htmltools_0.5.5  httpuv_1.6.11    Matrix_1.5-4.1  
[21] pkgconfig_2.0.3  mvtnorm_1.2-2    scales_1.2.1     processx_3.8.1  
[25] whisker_0.4.1    later_1.3.1      tzdb_0.4.0       timechange_0.2.0
[29] git2r_0.32.0     mgcv_1.8-42      farver_2.1.1     generics_0.1.3  
[33] TH.data_1.1-2    cachem_1.0.8     withr_2.5.0      cli_3.6.1       
[37] survival_3.5-5   magrittr_2.0.3   evaluate_0.21    ps_1.7.5        
[41] fs_1.6.2         fansi_1.0.4      nlme_3.1-162     tools_4.2.2     
[45] hms_1.1.3        lifecycle_1.0.3  multcomp_1.4-24  munsell_0.5.0   
[49] plotrix_3.8-2    callr_3.7.3      compiler_4.2.2   jquerylib_0.1.4 
[53] rlang_1.1.1      grid_4.2.2       rstudioapi_0.14  labeling_0.4.2  
[57] rmarkdown_2.22   gtable_0.3.3     codetools_0.2-19 abind_1.4-5     
[61] R6_2.5.1         zoo_1.8-12       knitr_1.43       fastmap_1.1.1   
[65] utf8_1.2.3       rprojroot_2.0.3  stringi_1.7.12   Rcpp_1.0.10     
[69] vctrs_0.6.3      tidyselect_1.2.0 xfun_0.39