The goal of the project is to identify deubiquitinases(DUBs) networks that could be targetable in cancer. There are about ~90 DUBs encoded in the human genome and many of these participate in critical cancer processes. Our preliminary data in a CRISPR/Cas9 essentiality screen suggests that only a handful of DUBs are actually essential for cancer cell survival suggesting some functional redundancy among DUBs. To identify possible functionally interacting DUBs, we performed a pooled combinatorial knockout screen using a CRISPR/Cas12a system (with Sci Life CRISPR Functional genomics). Here we use a custom guide library targeting any combination of 160 genes (including ~90 DUBs and other genes of interest). We want to identify lethal and growth-promoting knockout combinations, and define whether or not the interaction is a result of the additive effect of individual knockouts. Furthermore, we want to create a network of interacting DUBs from this.