Last updated: 2022-07-05

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Knit directory: BH3profiling/analysis/

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Load and preprocess BH3 profiling data

Load

Prepare sample background annotations

Compare Cyt C release with drug only, peptide only and drug+peptide

Dynamic BH3 profiling data

Apoptosis with drug only, venetoclax only and drug + venetoclax

Test for combination effect within BH3 profiling

Whether combination is explained by peptide or drug treatment

Test for combination effect

Plot top 10 most significant results

Synergy in Annexin data

Plot top 10 most significant results

Compare with drug sensitivity group from JCI

Load drug group data

Delta value (drug with peptide) - peptide alone

Associate syngergistic effect with genomics

Calculate combination index (CI) for each sample and combination

Table of associations

P value histogram

All

Box plots for the significant associations (P < 0.01)

If multiple concentrations are identified as significant, only show the most significant concentration.

Compare the predicting power of baseline,dynamic BH3 and delta values for specific drugs (Ibrutinib, Everolimus, Selumetinib)

Data preprocessing

BH3 profile

Drug respones

Test model

Show results

Change of R2 (Combined effect)

Change of R2 (delta value)

Bar plot of explained variance

Bar plot of explained variance (ordered by delta value)


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] latex2exp_0.9.4             forcats_0.5.1              
 [3] stringr_1.4.0               dplyr_1.0.9                
 [5] purrr_0.3.4                 readr_2.1.2                
 [7] tidyr_1.2.0                 tibble_3.1.7               
 [9] tidyverse_1.3.1             SummarizedExperiment_1.26.1
[11] Biobase_2.56.0              GenomicRanges_1.48.0       
[13] GenomeInfoDb_1.32.2         IRanges_2.30.0             
[15] S4Vectors_0.34.0            BiocGenerics_0.42.0        
[17] MatrixGenerics_1.8.0        matrixStats_0.62.0         
[19] limma_3.52.2                pheatmap_1.0.12            
[21] ggpubr_0.4.0                ggplot2_3.3.6              
[23] cowplot_1.1.1               corrplot_0.92              
[25] jyluMisc_0.1.5             

loaded via a namespace (and not attached):
  [1] readxl_1.4.0           backports_1.4.1        fastmatch_1.1-3       
  [4] drc_3.0-1              workflowr_1.7.0        igraph_1.3.2          
  [7] shinydashboard_0.7.2   splines_4.2.0          crosstalk_1.2.0       
 [10] BiocParallel_1.30.3    TH.data_1.1-1          digest_0.6.29         
 [13] htmltools_0.5.2        fansi_1.0.3            magrittr_2.0.3        
 [16] cluster_2.1.3          tzdb_0.3.0             modelr_0.1.8          
 [19] sandwich_3.0-2         piano_2.12.0           colorspace_2.0-3      
 [22] rvest_1.0.2            haven_2.5.0            xfun_0.31             
 [25] crayon_1.5.1           RCurl_1.98-1.7         jsonlite_1.8.0        
 [28] survival_3.3-1         zoo_1.8-10             glue_1.6.2            
 [31] survminer_0.4.9        gtable_0.3.0           zlibbioc_1.42.0       
 [34] XVector_0.36.0         DelayedArray_0.22.0    car_3.1-0             
 [37] abind_1.4-5            scales_1.2.0           mvtnorm_1.1-3         
 [40] DBI_1.1.3              relations_0.6-12       rstatix_0.7.0         
 [43] Rcpp_1.0.8.3           plotrix_3.8-2          xtable_1.8-4          
 [46] km.ci_0.5-6            DT_0.23                htmlwidgets_1.5.4     
 [49] httr_1.4.3             fgsea_1.22.0           gplots_3.1.3          
 [52] RColorBrewer_1.1-3     ellipsis_0.3.2         farver_2.1.0          
 [55] pkgconfig_2.0.3        sass_0.4.1             dbplyr_2.2.0          
 [58] utf8_1.2.2             labeling_0.4.2         tidyselect_1.1.2      
 [61] rlang_1.0.2            later_1.3.0            munsell_0.5.0         
 [64] cellranger_1.1.0       tools_4.2.0            visNetwork_2.1.0      
 [67] cli_3.3.0              generics_0.1.2         broom_0.8.0           
 [70] evaluate_0.15          fastmap_1.1.0          yaml_2.3.5            
 [73] knitr_1.39             fs_1.5.2               survMisc_0.5.6        
 [76] caTools_1.18.2         mime_0.12              slam_0.1-50           
 [79] xml2_1.3.3             compiler_4.2.0         rstudioapi_0.13       
 [82] ggsignif_0.6.3         marray_1.74.0          reprex_2.0.1          
 [85] bslib_0.3.1            stringi_1.7.6          highr_0.9             
 [88] lattice_0.20-45        Matrix_1.4-1           shinyjs_2.1.0         
 [91] KMsurv_0.1-5           vctrs_0.4.1            pillar_1.7.0          
 [94] lifecycle_1.0.1        jquerylib_0.1.4        data.table_1.14.2     
 [97] bitops_1.0-7           httpuv_1.6.5           R6_2.5.1              
[100] promises_1.2.0.1       KernSmooth_2.23-20     gridExtra_2.3         
[103] codetools_0.2-18       MASS_7.3-57            gtools_3.9.2.2        
[106] exactRankTests_0.8-35  assertthat_0.2.1       rprojroot_2.0.3       
[109] withr_2.5.0            multcomp_1.4-19        GenomeInfoDbData_1.2.8
[112] parallel_4.2.0         hms_1.1.1              grid_4.2.0            
[115] rmarkdown_2.14         carData_3.0-5          git2r_0.30.1          
[118] maxstat_0.7-25         sets_1.0-21            shiny_1.7.1           
[121] lubridate_1.8.0