Associations between baseline BH3 (from DBP) and drug responses (Individual concentrations)
Junyan Lu
2020 Sept 3
Last updated: 2020-09-30
Checks: 5 2
Knit directory: BH3profiling/analysis/
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Load and preprocess BH3 profiling data
Load
Use baseline level from DBP profiling
Prepare sample background annotations
Association with ex-vivo drug responses (IC50 screen)
Preprocessing
[1] 52P-value histogram
Table of significant correlations
Summarise plot for all concentrations
Scatter plots showing significant correlations (1% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
x-axis is the cell viability after drug treatment, so higher values mean higher drug resistance
Association with ex-vivo drug responses (1000CPS screen)
Preprocessing
[1] 59[1] 26 59P-value histogram
Table of significant correlations
Summarise plot for all concentrations
Scatter plots showing significant correlations (5% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
x-axis is the cell viability after drug treatment, so higher values mean higher drug resistance
Association with cytokine screen
Preprocessing
[1] 60[1] 521 60[1] 26 60P-value histogram
Table of significant correlations
Summarise plot for all concentrations (Cytokines alone)
Scatter plots showing significant correlations (5% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
x-axis is the cell viability after drug treatment, so higher values mean higher drug resistance
Summarise plot for all concentrations (Drug alone)
Scatter plots showing significant correlations (5% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
x-axis is the cell viability after drug treatment, so higher values mean higher drug resistance
If multiple concentrations are identified as significant, only show the most significant concentration. 
Scatter plots showing significant correlations (5% FDR), with venetoclax
If multiple concentrations are identified as significant, only show the most significant concentration. 
Association with ex-vivo drug responses (Annexin data)
Preprocessing
[1] 26 31Correlation with baseline viablity (DMSO only treatment)
Table of significant correlations
Scatter plots showing significant correlations (5% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
Correlation with drug treatment
Table of significant correlations
P-value histogram
Summarise plot for all concentrations
Scatter plots showing significant correlations (P < 0.05)
If multiple concentrations are identified as significant, only show the most significant concentration. 
Correlation with Venetoclax treatment only
Table of significant correlations
P-value histogram
Summarise plot for all concentrations
Scatter plots showing top9 significant correlations
If multiple concentrations are identified as significant, only show the most significant concentration. 
Correlation with combined effect
Table of significant correlations
P-value histogram
Summarise plot for all concentrations
Scatter plots showing significant correlations (1% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
Correlation with synergistic effect (combination index: CI)
Table of significant correlations
P-value histogram
Summarise plot for all concentrations
Scatter plots showing significant correlations (10% FDR)
If multiple concentrations are identified as significant, only show the most significant concentration. 
Higher CI value means more synergy in drug combinations
In vivo responses
Table of significant associations (P<0.05)
P-value histogram
Scatter plots showing significant associations (p <0.05)
If multiple concentrations are identified as significant, only show the most significant concentration. 
In vivo responses and annexin data
Table of significant associations (P<0.05)
Scatter plots showing significant associations (p <0.05)
If multiple concentrations are identified as significant, only show the most significant concentration. 
Comparability between viability screen and Annexin data
IC50 screen
For kinase inhibitors
No venetoclax 
With 10 nM venetoclax 
For Venetoclax
Look comparable for most of the concentrations.
1000CPS screen
For kinase inhibitors
No venetoclax 
With 10 nM venetoclax 
For Venetoclax
Something strange about venetoclax in 1000CPS screen.
Multi-variate analysis for predicting drug responses
Test whether the BH3 profile can explain additional variance in drug response compared to genetic alone
IC50 screen
Data prepare
[1] 52Prepare genomics
Genes that will be included in the multivariate model
[1] "IGHV.status" "del11q" "del13q" "del17p" "trisomy12"
[6] "NOTCH1" "SF3B1" "TP53" Test
Which peptides and concentrations are more informative?
This can help with concentration selection. We want to select the concentration that shows most significant associations.
1000CPS screen
Data prepare
[1] 59Prepare genomics
Genes that will be included in the multivariate model
[1] "IGHV.status" "del11q" "del13q" "del17p" "trisomy12"
[6] "NOTCH1" "SF3B1" "TP53" Test
Which peptides and concentrations are more informative?
R version 3.6.0 (2019-04-26)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS 10.15.6
Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.6/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 stats4 stats graphics grDevices utils datasets
[8] methods base
other attached packages:
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[3] stringr_1.4.0 dplyr_1.0.0
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loaded via a namespace (and not attached):
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