Last updated: 2022-07-25

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Knit directory: BH3profiling/analysis/

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Read in clincal trial data

Read in outcome

Only primary endpoint

Read in BH3 profiling data

Ex-vivo baseline

In vivo

Calculate robust z-score

Set outlier values to NA

Ex vivo with Ibrutinib

Read background

Some samples need to be excluded

Final patient number

[1] 53

Heatmap

Baseline

Test associations with IGHV

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

In vivo

Test associations with IGHV

Test for associations

Generate heatmap

Plot example associations

Test for associations (adjusted for IGHV)

Does MRD status associated with IGHV status?

# A tibble: 6 × 3
# Groups:   endpoint, response [6]
  endpoint                                              response p.value
  <chr>                                                 <chr>      <dbl>
1 "Best response"                                       MRD BM     0.129
2 "End of combination therapy\n(post-FCR)"              MRD PB     0.210
3 "Best response"                                       MRD PB     0.394
4 "Halfway through combination therapy\n(post cycle 3)" MRD BM     0.402
5 "Halfway through combination therapy\n(post cycle 3)" MRD PB     0.514
6 "End of combination therapy\n(post-FCR)"              MRD BM     0.588

Whether combining BH3 profiling and IGHV status can better predict outcome?

Cases that combining IGVH and BH3 profiling is better than each alone

# A tibble: 9 × 7
# Groups:   feature, set, endpoint, response [9]
  feature       set      endpoint                   respo…¹  r2Pep r2IGHV  r2Com
  <chr>         <chr>    <chr>                      <chr>    <dbl>  <dbl>  <dbl>
1 BIM_0.05_µM   Baseline "Best response"            MRD BM  0.0366 0.0809 0.123 
2 BIM_0.1_µM    Baseline "Best response"            MRD BM  0.0344 0.0812 0.0923
3 A-133_0.01_µM Baseline "Best response"            MRD BM  0.0584 0.0809 0.0912
4 ABT199_1_µM18 In_vivo  "Best response"            MRD BM  0.0701 0.0774 0.0872
5 BAD_1_µM7     In_vivo  "Best response"            MRD BM  0.0648 0.0774 0.0864
6 A-133_0.01_µM Baseline "End of combination thera… MRD PB  0.0711 0.0610 0.0816
7 PUMA_0.1_µM   Baseline "End of combination thera… MRD PB  0.0588 0.0610 0.0624
8 HRK-y_10_µM12 In_vivo  "End of combination thera… MRD PB  0.0515 0.0583 0.0604
9 BIM_0.05_µM   Baseline "Halfway through combinat… MRD PB  0.0301 0.0348 0.0423
# … with abbreviated variable name ¹​response

Plot difference of R2 


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] ggplot2_3.3.6               tidyverse_1.3.2            
[11] SummarizedExperiment_1.26.1 Biobase_2.56.0             
[13] GenomicRanges_1.48.0        GenomeInfoDb_1.32.2        
[15] IRanges_2.30.0              S4Vectors_0.34.0           
[17] BiocGenerics_0.42.0         MatrixGenerics_1.8.1       
[19] matrixStats_0.62.0          IHW_1.24.0                 
[21] limma_3.52.2                readxl_1.4.0               
[23] pheatmap_1.0.12             cowplot_1.1.1              
[25] jyluMisc_0.1.5             

loaded via a namespace (and not attached):
  [1] backports_1.4.1        fastmatch_1.1-3        drc_3.0-1             
  [4] workflowr_1.7.0        igraph_1.3.4           shinydashboard_0.7.2  
  [7] splines_4.2.0          BiocParallel_1.30.3    TH.data_1.1-1         
 [10] lpsymphony_1.24.0      digest_0.6.29          htmltools_0.5.3       
 [13] fansi_1.0.3            magrittr_2.0.3         googlesheets4_1.0.0   
 [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           gargle_1.2.0          
 [34] zlibbioc_1.42.0        XVector_0.36.0         DelayedArray_0.22.0   
 [37] car_3.1-0              abind_1.4-5            scales_1.2.0          
 [40] mvtnorm_1.1-3          DBI_1.1.3              relations_0.6-12      
 [43] rstatix_0.7.0          Rcpp_1.0.9             plotrix_3.8-2         
 [46] xtable_1.8-4           km.ci_0.5-6            DT_0.23               
 [49] htmlwidgets_1.5.4      httr_1.4.3             fgsea_1.22.0          
 [52] gplots_3.1.3           RColorBrewer_1.1-3     ellipsis_0.3.2        
 [55] farver_2.1.1           pkgconfig_2.0.3        sass_0.4.2            
 [58] dbplyr_2.2.1           utf8_1.2.2             labeling_0.4.2        
 [61] tidyselect_1.1.2       rlang_1.0.4            later_1.3.0           
 [64] munsell_0.5.0          cellranger_1.1.0       tools_4.2.0           
 [67] visNetwork_2.1.0       cachem_1.0.6           cli_3.3.0             
 [70] generics_0.1.3         broom_1.0.0            fdrtool_1.2.17        
 [73] evaluate_0.15          fastmap_1.1.0          yaml_2.3.5            
 [76] knitr_1.39             fs_1.5.2               survMisc_0.5.6        
 [79] caTools_1.18.2         egg_0.4.5              mime_0.12             
 [82] slam_0.1-50            xml2_1.3.3             compiler_4.2.0        
 [85] rstudioapi_0.13        ggsignif_0.6.3         marray_1.74.0         
 [88] reprex_2.0.1           bslib_0.4.0            stringi_1.7.8         
 [91] highr_0.9              lattice_0.20-45        Matrix_1.4-1          
 [94] shinyjs_2.1.0          KMsurv_0.1-5           vctrs_0.4.1           
 [97] pillar_1.8.0           lifecycle_1.0.1        jquerylib_0.1.4       
[100] data.table_1.14.2      bitops_1.0-7           httpuv_1.6.5          
[103] R6_2.5.1               promises_1.2.0.1       KernSmooth_2.23-20    
[106] gridExtra_2.3          codetools_0.2-18       MASS_7.3-58           
[109] gtools_3.9.3           exactRankTests_0.8-35  assertthat_0.2.1      
[112] rprojroot_2.0.3        withr_2.5.0            multcomp_1.4-19       
[115] GenomeInfoDbData_1.2.8 parallel_4.2.0         hms_1.1.1             
[118] grid_4.2.0             rmarkdown_2.14         carData_3.0-5         
[121] googledrive_2.0.0      git2r_0.30.1           maxstat_0.7-25        
[124] ggpubr_0.4.0           sets_1.0-21            shiny_1.7.2           
[127] lubridate_1.8.0        rematch_1.0.1