Last updated: 2023-01-18

Checks: 5 1

Knit directory: LungCancer_SotilloLab/analysis/

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Load packages and dataset

Packages

#package
library(SummarizedExperiment)
library(MultiAssayExperiment)
library(proDA)
library(UpSetR)
library(tidyverse)
source("../code/utils.R")
knitr::opts_chunk$set(warning = FALSE, message = FALSE, autodep = TRUE)

Preprocessed data

load("../output/processedData_RUN5.RData")

#load saved result list
load("../output/allResList_RUN5_timeBased.RData")
#a list to collect all results
#allResList <- list()

We hypothesize that dasatinib is inhibiting other proteins apart from SRC. Check the status (global/phospho) of the described off targets in dasatinib or combo treated cells: ABL1, ABL2, BLK, EPHA2, FGR, FRK, FYN, HCK, KIT, LCK, LYN, PDGFRB, SRC, SRMS, STAT5B, YES1, EGFR

Prepare gene list

geneList <- sort(c("Abl1", "Abl2", "Blk", "Epha2", "Fgr", "Frk", "Fyn",
              "Hck", "Kit", "Lck", "Lyn", "Pdgfrb", "Src", "Srms", "Stat5b", "Yes1", "Egfr","Akt1","Akt2","Akt3",
              "Stat1","Stat3","Stat5a","Stat5b","Mapk1","Mapk3","Mapk4","Pik3ca","Pik3cb","Pik3c3","Pik3c2a",
              "Pik3r2","Pik3r1","Pik3c2g","Jak1","Rasa1","Rasa2","Rasa3","Rhoa","Rhob","Rhoc","Rhog","Rhod"))

Prepare datasets

Proteome

fpeSub <- preprocessProteome(maeData, filterList = list(drug =c("brigatinib","dasatinib","DMSO")), missCut = 1, transform = "vst", normalize = TRUE)
[1] "Number of proteins and samples:"
[1] 8028   66
fpeDMSO <- fpeSub[,fpeSub$drug=="DMSO"]

fpeBri0 <- fpeDMSO
colnames(fpeBri0) <- str_replace(colnames(fpeBri0),"DMSO","dasatinib")
fpeBri0$drug <- "dasatinib"

#0 time for brigatinib
fpeCombo0 <- fpeDMSO
colnames(fpeCombo0) <- str_replace(colnames(fpeCombo0),"DMSO","brigatinib")
fpeCombo0$drug <- "brigatinib"


#combine a new fpe data
fpeDrug <- fpeSub[,fpeSub$drug!="DMSO"]
fpeNew <- cbind(fpeDrug, fpeBri0, fpeCombo0)

Phosphoproteome

ppeSub <- preprocessPhos(maeData, filterList = list(drug =c("dasatinib","brigatinib","DMSO")), 
                         missCut = 1, transform = "vst", normalize = TRUE)
[1] "Number of proteins and samples:"
[1] 19619    66
ppeDMSO <- ppeSub[,ppeSub$drug=="DMSO"]

#0 time for dasatinib
ppeBri0 <- ppeDMSO
colnames(ppeBri0) <- str_replace(colnames(ppeBri0),"DMSO","dasatinib")
ppeBri0$drug <- "dasatinib"

#0 time for brigatinib
ppeCombo0 <- ppeDMSO
colnames(ppeCombo0) <- str_replace(colnames(ppeCombo0),"DMSO","brigatinib")
ppeCombo0$drug <- "brigatinib"


#combine a new ppe data
ppeDrug <- ppeSub[,ppeSub$drug!="DMSO"]
ppeNew <- cbind(ppeDrug, ppeBri0, ppeCombo0)

Create plots

pList <- plotPhosProt(geneList, fpeNew, ppeNew, averageReplicate = TRUE)

Plot the selected genes

jyluMisc::makepdf(pList, "../docs/Dasatinib_effect_RUN5.pdf", ncol = 1, nrow=3, height = 20, width = 12)

pdf plot


sessionInfo()
R version 4.2.0 (2022-04-22)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Big Sur/Monterey 10.16

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.2/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.2/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] stats4    stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] forcats_0.5.1               stringr_1.4.1              
 [3] dplyr_1.0.9                 purrr_0.3.4                
 [5] readr_2.1.2                 tidyr_1.2.0                
 [7] tibble_3.1.8                ggplot2_3.3.6              
 [9] tidyverse_1.3.2             UpSetR_1.4.0               
[11] proDA_1.10.0                MultiAssayExperiment_1.22.0
[13] SummarizedExperiment_1.26.1 Biobase_2.56.0             
[15] GenomicRanges_1.48.0        GenomeInfoDb_1.32.2        
[17] IRanges_2.30.0              S4Vectors_0.34.0           
[19] BiocGenerics_0.42.0         MatrixGenerics_1.8.1       
[21] matrixStats_0.62.0         

loaded via a namespace (and not attached):
  [1] DEP_1.18.0             utf8_1.2.2             shinydashboard_0.7.2  
  [4] gmm_1.6-6              tidyselect_1.1.2       htmlwidgets_1.5.4     
  [7] grid_4.2.0             BiocParallel_1.30.3    norm_1.0-10.0         
 [10] maxstat_0.7-25         munsell_0.5.0          codetools_0.2-18      
 [13] preprocessCore_1.58.0  DT_0.23                withr_2.5.0           
 [16] colorspace_2.0-3       knitr_1.39             rstudioapi_0.13       
 [19] ggsignif_0.6.3         mzID_1.34.0            git2r_0.30.1          
 [22] slam_0.1-50            GenomeInfoDbData_1.2.8 KMsurv_0.1-5          
 [25] rprojroot_2.0.3        vctrs_0.4.1            generics_0.1.3        
 [28] TH.data_1.1-1          xfun_0.31              sets_1.0-21           
 [31] R6_2.5.1               doParallel_1.0.17      clue_0.3-61           
 [34] MsCoreUtils_1.8.0      fgsea_1.22.0           bitops_1.0-7          
 [37] cachem_1.0.6           DelayedArray_0.22.0    assertthat_0.2.1      
 [40] promises_1.2.0.1       scales_1.2.0           multcomp_1.4-19       
 [43] googlesheets4_1.0.0    gtable_0.3.0           affy_1.74.0           
 [46] sandwich_3.0-2         workflowr_1.7.0        rlang_1.0.6           
 [49] mzR_2.30.0             GlobalOptions_0.1.2    splines_4.2.0         
 [52] rstatix_0.7.0          gargle_1.2.0           impute_1.70.0         
 [55] broom_1.0.0            BiocManager_1.30.18    yaml_2.3.5            
 [58] abind_1.4-5            modelr_0.1.8           backports_1.4.1       
 [61] httpuv_1.6.6           tools_4.2.0            relations_0.6-12      
 [64] affyio_1.66.0          ellipsis_0.3.2         gplots_3.1.3          
 [67] jquerylib_0.1.4        RColorBrewer_1.1-3     MSnbase_2.22.0        
 [70] Rcpp_1.0.9             plyr_1.8.7             visNetwork_2.1.0      
 [73] zlibbioc_1.42.0        RCurl_1.98-1.7         ggpubr_0.4.0          
 [76] GetoptLong_1.0.5       cowplot_1.1.1          zoo_1.8-10            
 [79] haven_2.5.0            cluster_2.1.3          exactRankTests_0.8-35 
 [82] fs_1.5.2               magrittr_2.0.3         data.table_1.14.2     
 [85] circlize_0.4.15        survminer_0.4.9        reprex_2.0.1          
 [88] googledrive_2.0.0      pcaMethods_1.88.0      mvtnorm_1.1-3         
 [91] ProtGenerics_1.28.0    shinyjs_2.1.0          hms_1.1.1             
 [94] mime_0.12              evaluate_0.15          xtable_1.8-4          
 [97] XML_3.99-0.10          readxl_1.4.0           gridExtra_2.3         
[100] shape_1.4.6            compiler_4.2.0         KernSmooth_2.23-20    
[103] ncdf4_1.19             crayon_1.5.2           htmltools_0.5.3       
[106] later_1.3.0            tzdb_0.3.0             lubridate_1.8.0       
[109] DBI_1.1.3              dbplyr_2.2.1           ComplexHeatmap_2.12.0 
[112] MASS_7.3-58            tmvtnorm_1.5           jyluMisc_0.1.5        
[115] Matrix_1.4-1           car_3.1-0              cli_3.4.1             
[118] vsn_3.64.0             imputeLCMD_2.1         marray_1.74.0         
[121] parallel_4.2.0         igraph_1.3.4           km.ci_0.5-6           
[124] pkgconfig_2.0.3        piano_2.12.0           MALDIquant_1.21       
[127] xml2_1.3.3             foreach_1.5.2          bslib_0.4.1           
[130] XVector_0.36.0         drc_3.0-1              rvest_1.0.2           
[133] digest_0.6.30          fastmatch_1.1-3        rmarkdown_2.14        
[136] cellranger_1.1.0       survMisc_0.5.6         shiny_1.7.3           
[139] gtools_3.9.3           rjson_0.2.21           lifecycle_1.0.3       
[142] jsonlite_1.8.3         carData_3.0-5          limma_3.52.2          
[145] fansi_1.0.3            pillar_1.8.0           lattice_0.20-45       
[148] fastmap_1.1.0          httr_1.4.3             plotrix_3.8-2         
[151] survival_3.4-0         glue_1.6.2             png_0.1-7             
[154] iterators_1.0.14       stringi_1.7.8          sass_0.4.2            
[157] caTools_1.18.2