Dear DepMap community,
Initially I would like to wish to everyone a happy new year with health above all !!
Concerning my post, based on an ongoing collaborative project, within a specific cancer type, we have ranked and scored specific mutated genes based on distinct clinical subgroups-which are defined based on the mutational status of known cancer driver genes (i.e. GeneA_mutated_group, GeneB_mutated_group and WT)
Our ultimate goal is to further exploit and validate:
Based on the DepMap portal genetic screens to investigate if any of these identified top ranked genes in each category, could be considered as “selective essential genes” and interesting putative drug targets for further exploitation and hypothesis generation in each clinical subgroup;
Further utilize the DepMap portal resources to further identify any perturbagens that might target these genes of interest;
On this direction, one direct approach would be from custom analysis, to select these cancer cell lines-for example in colorectal cancer-that harbor mutations in gene A vs the same cancer cell lines that have mutations in gene B (which have been mentioned as clinical subgroups from above) and perform a two-group comparison:
Based also on my attached example
volcano plot for some random cell line comparisons, my major questions are the following:
A) For my research goal and hypothesis comparison, the appropriate dataset would be the selected CRISPR (DepMap 21Q4 + Score, Chronos)?
B) For these genes that show a q value <=0.05, it could be translated as these genes show a “preferential essentiality” in the compared cell lines? That is based on the CRISPR latest dataset genetic screen dependencies? And then directly compare these hits with our top prioritized top mutated genes to highlight common targets? That are “clinical group/subtype” specific?
C) In addition to step B there could be a further way to decipher and remove any targets resulted, that could be “pan-cancer” or generally essential in most cancer cell lines and might produce a “toxic effect”? In order to balance efficacy with essentiality ?
Thank you in advance for your time and consideration:)