Figure 1. Identification of EGLN1 as a preferential cancer cell dependency.
A. Identification of EGLN1 dependency in RNAi data from Project Achilles. From the initial ~17k genes tested, we found 762 were strong (Six Sigma) dependencies using DEMETER scores. From these dependencies, we found 153 were currently druggable, while 15 of them had compounds in clinical trials. We identified EGLN1 as one of these 15 clinically druggable dependencies.
B. Identification of cancer cells dependent on EGLN1 using CRISPR-Cas9 data from Project Achilles. Histogram shows the distribution of EGLN1 CERES dependencies (X-axis) across 436 cancer cell lines screened with CRISPR. The left tail shows that a subset of lines are preferentially dependent on EGLN1.
C. Concordance between RNAi and CRISPR-Cas9 datasets. EGLN1 DEMETER2 scores are graphed against EGLN1 CERES scores (CRISPR, X-axis) for the 243 cell lines screened in both datasets. The correlation between the datasets was strong and highly significant. Pearson = 0.512. n=243, p<10−21.
D. Volcano plot showing cancer dependencies associated with EGLN1 dependency graphed as p-value (-log10, Y-axis) against effect size (X-axis). Colored in red are other members of the EGLN1 pathway.
E. EGLN1 and VHL are the strongest correlated dependencies within the EGLN1 pathway while EGLN1 and HIF1AN are the second strongest correlated dependencies. P-values were adjusted using the Benjamini and Hochberg FDR method. FDR < 0.05 (*), 0.01 (**), 0.001 (***).
F. Cell lines that express low levels of HIF1A (Y-axis) are not dependent on EGLN1 (X-axis).