dose_escalation_verification

Last updated: 2024-09-02

Checks: 6 1

Knit directory: duplex_sequencing_screen/

This reproducible R Markdown analysis was created with workflowr (version 1.6.2). The Checks tab describes the reproducibility checks that were applied when the results were created. The Past versions tab lists the development history.

R Markdown file: uncommitted changes

The R Markdown file has unstaged changes. To know which version of the R Markdown file created these results, you’ll want to first commit it to the Git repo. If you’re still working on the analysis, you can ignore this warning. When you’re finished, you can run wflow_publish to commit the R Markdown file and build the HTML.

Environment: empty

Great job! The global environment was empty. Objects defined in the global environment can affect the analysis in your R Markdown file in unknown ways. For reproduciblity it’s best to always run the code in an empty environment.

Seed: set.seed(20200402)

The command set.seed(20200402) was run prior to running the code in the R Markdown file. Setting a seed ensures that any results that rely on randomness, e.g. subsampling or permutations, are reproducible.

Session information: recorded

Great job! Recording the operating system, R version, and package versions is critical for reproducibility.

Cache: none

Nice! There were no cached chunks for this analysis, so you can be confident that you successfully produced the results during this run.

File paths: relative

Great job! Using relative paths to the files within your workflowr project makes it easier to run your code on other machines.

Repository version: b998df6

Great! You are using Git for version control. Tracking code development and connecting the code version to the results is critical for reproducibility.

The results in this page were generated with repository version b998df6. See the Past versions tab to see a history of the changes made to the R Markdown and HTML files.

Note that you need to be careful to ensure that all relevant files for the analysis have been committed to Git prior to generating the results (you can use wflow_publish or wflow_git_commit). workflowr only checks the R Markdown file, but you know if there are other scripts or data files that it depends on. Below is the status of the Git repository when the results were generated:


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These are the previous versions of the repository in which changes were made to the R Markdown (analysis/dose_escalation_verification.Rmd) and HTML (docs/dose_escalation_verification.html) files. If you’ve configured a remote Git repository (see ?wflow_git_remote), click on the hyperlinks in the table below to view the files as they were in that past version.

File	Version	Author	Date	Message
Rmd	1e2bfaa	haiderinam	2023-11-02	Lane 29a Ponatilink variant calls added
Rmd	f535532	haiderinam	2023-09-06	Parsed ABL region 2 3 4 variant calls

# source("code/cosmic_data_adder.R")
candidates=c("F311L",
             "F311I",
              "F317L",
              "F317C",
              "L273M",
              "E279A",
              "E275K",
              "E279K",
              "E258A",
              "D276N",
              "T277A",
              "V289F",
              "L248R",
              "T319I",
              "E292V",
              "E275Q",
              "Y253N",
              "K247R")

Looking at mutant candidates for dose escalation

# low
a=read.csv("output/ABLEnrichmentScreens/ABL_Region1_Lane18_Comparisons/cross-replicate/baf3_Imat_low_rep1vsrep2_ft/screen_comparison_baf3_Imat_low_rep1vsrep2_ft.csv",header = T,stringsAsFactors = F)

a=a%>%filter(species%in%candidates)
a=a%>%dplyr::select(species,netgr_obs_mean)
a$dose=300
# medium
b=read.csv("output/ABLEnrichmentScreens/ABL_Region1_Lane18_Comparisons/cross-replicate/baf3_Imat_medium_rep1vsrep2_ft/screen_comparison_baf3_Imat_medium_rep1vsrep2_ft.csv",header = T,stringsAsFactors = F)

b=b%>%filter(species%in%candidates)
b=b%>%dplyr::select(species,netgr_obs_mean)
b$dose=600
# High
c=read.csv("output/ABLEnrichmentScreens/ABL_Region1_Lane18_Comparisons/cross-replicate/baf3_Imat_high_rep1vsrep2_ft/screen_comparison_baf3_Imat_high_rep1vsrep2_ft.csv",header = T,stringsAsFactors = F)

c=c%>%filter(species%in%candidates)
c=c%>%dplyr::select(species,netgr_obs_mean)
c$dose=1200


# No drug
d=read.csv("output/ABLEnrichmentScreens/ABL_Region1_Lane18_Comparisons/cross-replicate/baf3_IL3_rep1vsrep2_ft/screen_comparison_baf3_IL3_low_rep1vsrep2_ft.csv",header = T,stringsAsFactors = F)

d=d%>%filter(species%in%candidates)
d=d%>%dplyr::select(species,netgr_obs_mean)
d$dose=0

# No drug
e=read.csv("output/ABLEnrichmentScreens/ABL_Region1_Lane18_Comparisons/cross-replicate/baf3_IL3_rep1vsrep2_ft/screen_comparison_baf3_IL3_low_rep1vsrep2_ft.csv",header = T,stringsAsFactors = F)

e=e%>%filter(species%in%candidates)
e=e%>%dplyr::select(species,netgr_wodrug=netgr_obs_mean)

allmuts=rbind(a,b,c,d)
allmuts$y=exp(-(0.068-allmuts$netgr_obs_mean)*72)

allmuts=merge(allmuts,e,by="species")
allmuts=allmuts%>%mutate(y_new=exp((netgr_wodrug-netgr_obs_mean)*-72))

ggplot(allmuts,aes(x=dose,y=netgr_obs_mean))+geom_point()+facet_wrap(~species)

ggplot(allmuts%>%filter(!dose%in%0),aes(x=dose,y=y))+geom_point()+facet_wrap(~species)

plotly=ggplot(allmuts%>%filter(!dose%in%0),aes(x=dose,y=y_new))+geom_point()+facet_wrap(~species)
ggplotly(plotly)

Warning: `group_by_()` was deprecated in dplyr 0.7.0.
Please use `group_by()` instead.
See vignette('programming') for more help

plotly=ggplot(allmuts,aes(x=dose,y=y_new))+
  geom_point()+
  facet_wrap(~species)+
  scale_x_continuous(trans="log10")
ggplotly(plotly)

Warning: Transformation introduced infinite values in continuous x-axis

plotly=ggplot(allmuts%>%filter(!dose%in%0),aes(x=dose,y=y))+
  geom_point()+
  facet_wrap(~species)+
  scale_x_continuous(trans="log10")
ggplotly(plotly)

# Basciallly there are two ways of plotting y (proportion alive) from our screens. One is to assume the same fitness without drug for all mutants, another is to assume fitness without drug that are different for all mutants.
# newdf=cosmic_data_adder(df)

Plotting IC50 fitnesses

sessionInfo()

R version 4.0.0 (2020-04-24)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS  10.16

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib

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

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

other attached packages:
 [1] pROC_1.16.2        ggpubr_0.4.0       RColorBrewer_1.1-2 doParallel_1.0.15 
 [5] iterators_1.0.12   foreach_1.5.0      tictoc_1.0         plotly_4.9.2.1    
 [9] ggplot2_3.3.3      dplyr_1.0.6        stringr_1.4.0     

loaded via a namespace (and not attached):
 [1] httr_1.4.2        sass_0.4.1        tidyr_1.1.3       jsonlite_1.7.2   
 [5] viridisLite_0.3.0 carData_3.0-3     bslib_0.3.1       assertthat_0.2.1 
 [9] cellranger_1.1.0  yaml_2.2.1        pillar_1.6.1      backports_1.1.7  
[13] glue_1.4.1        digest_0.6.25     promises_1.1.0    ggsignif_0.6.0   
[17] colorspace_1.4-1  htmltools_0.5.2   httpuv_1.5.2      plyr_1.8.6       
[21] pkgconfig_2.0.3   broom_0.7.6       haven_2.4.1       purrr_0.3.4      
[25] scales_1.1.1      whisker_0.4       openxlsx_4.1.5    later_1.0.0      
[29] rio_0.5.16        git2r_0.27.1      tibble_3.1.2      generics_0.0.2   
[33] farver_2.0.3      car_3.0-7         ellipsis_0.3.2    withr_2.4.2      
[37] lazyeval_0.2.2    magrittr_2.0.1    crayon_1.4.1      readxl_1.3.1     
[41] evaluate_0.14     fs_1.4.1          fansi_0.4.1       rstatix_0.6.0    
[45] forcats_0.5.1     foreign_0.8-78    tools_4.0.0       data.table_1.14.8
[49] hms_1.1.0         lifecycle_1.0.0   munsell_0.5.0     zip_2.0.4        
[53] compiler_4.0.0    jquerylib_0.1.4   rlang_0.4.11      grid_4.0.0       
[57] htmlwidgets_1.5.1 crosstalk_1.1.0.1 labeling_0.3      rmarkdown_2.14   
[61] gtable_0.3.0      codetools_0.2-16  abind_1.4-5       DBI_1.1.0        
[65] curl_4.3          R6_2.4.1          knitr_1.28        fastmap_1.1.0    
[69] utf8_1.1.4        workflowr_1.6.2   rprojroot_1.3-2   stringi_1.7.5    
[73] Rcpp_1.0.4.6      vctrs_0.3.8       tidyselect_1.1.0  xfun_0.31

dose_escalation_verification

Haider Inam

2023-09-04