Workflow and rationale

Significantly up-regulated and down-regulated genes in Venetoclax Resistance leukemia specimens are uploaded to CLUE.io for analysis.

A positive connection score identifies a particular perturbagen (OE, KD or drug) may induce Venetoclax resistance.

A negative connection score identifies a particular perturbagen (OE, KD or drug) may induce Venetoclax sensitivity.

Over-expression of BCL2 family genes are generally positively connected with Ven-Res signature

Top 100 positively connected OE perturbagens (gene function may promote Ven resistance)

Top 100 negatively connected OE perturbagens (gene function may promotes Ven sensitivity)

Top 15 positively connected drugs (co-treatment may decrease Ven sensitivity)

Top 15 negatively connected drugs (co-treatment may increase Ven sensitivity)

!!! Note DNA methyltransferase inhibitor Zebularine (another analog of cytidine, just like Azacytidine) is the top 1 on the list! This maybe a strong evidence to explain why addition of Aza could synergize/sensitize AML patients to Venetoclax treatment?!

And all other Hypomethylating agents in the cMAPv2.0 database

Session Info

sessionInfo()
## R version 3.3.2 (2016-10-31)
## Platform: x86_64-apple-darwin13.4.0 (64-bit)
## Running under: macOS Sierra 10.12.6
## 
## 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] stats     graphics  grDevices utils     datasets  methods   base     
## 
## loaded via a namespace (and not attached):
##  [1] backports_1.1.2 magrittr_1.5    rprojroot_1.2   tools_3.3.2    
##  [5] htmltools_0.3.6 yaml_2.1.16     Rcpp_0.12.14    stringi_1.1.6  
##  [9] rmarkdown_1.8   knitr_1.17      stringr_1.2.0   digest_0.6.12  
## [13] evaluate_0.10.1