GPU-ENABLED DIFFERENTIAL DEPENDENCY NETWORK ANALYSIS OF LARGE - PowerPoint PPT Presentation

GPU-ENABLED DIFFERENTIAL DEPENDENCY NETWORK ANALYSIS OF LARGE DATASETS Gil Speyer May 9, 2017 Nvidia GTC – S7254

Transcriptomic Data Personome.com

Biological Pathways Nature.org

Differential expression analysis Class labels C1 C2 Pathway Differential analysis Expression GSEA Pathway p-value P 1 0.00002 P 2 0.0001 … … P k 0.01

Differential Coexpression and DDNs Biolayout.org

EDDY: discovery of differential dependency Prior ¡knowledge ¡ Known Gene set p-value gene-gene Gene Set DB Interactions G 1 0.00001 Gene set G 1 , G 2 , … G 2 0.00005 GIN i ¡ … g 1 ¡ G i = {g i ,1 , g i ,2 , …} ¡ … … g 3 ¡ C1 ¡ C2 ¡ g 2 ¡ G k 0.007 g 5 ¡ g 4 ¡ ¡ ¡ G j : DDN GDN i ¡ g 1 ¡ known ¡ g 3 ¡ interaction ¡ g 2 ¡ inferred ¡ Jung ¡et ¡al., ¡NAR ¡2014 ¡ g 5 ¡ dependency ¡ g 4 ¡ Speyer ¡et ¡al., ¡PSB ¡2016 ¡ C1 Statistical ¡ ¡ … test ¡ C2 ( ) P G D C 1 C1-specific Common C2-specific Network Likelihoods dependency dependency dependency

Transcriptomic Data

EDDY + CTRP-CCLE RNAseq of 935 cancer Cell lines chemical cell lines sensitivity for 481 small compounds – Identifies pathways enriched with differential dependency between sensitive and non-sensitive cancer cell lines, as in DDNs – Discover mediators of drug sensitivity, i.e. potential targets?

Drug Sensitivity Dose-Response Curve Viability (% DMSO) Cell line chemical sensitivity for 481 small compounds across >900 A rea U nder CCLs [TG − 101348 −− inhibitor of Janus kinase 2] C urve BRD − K12502280 ● ● ● Sensitive (125) ● ● EC50 ¡ IC50 ¡ Uncertain (596) ● ● NOT sensitive (126) 15 ● ● ● Concentration (log) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● auc ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 10 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0.3 0.2 0.1 0.0 0 200 400 600 800 BRD − K12502280