Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 15, Pages 8488-8504Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab627
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Funding
- Swiss Cancer League [KFS-4988-02-2020-R, KFS-4543-08-2018]
- Swiss National Science Foundation [PZ00P3_168165]
- AIRC (Fondazione AIRC per la Ricerca sul Cancro) [23615]
- European Research Council [609883]
- Theron Foundation, Vaduz (LI)
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Systematic perturbation screens provide resources for identifying cancer driver genes, requiring specialized computational tools for processing data from perturbation of many genes in few cell lines. APSiC is a statistical framework developed for identifying novel cancer genes and effectors in perturbation screens, demonstrated through analysis of the DRIVE project. The analysis of DRIVE using APSiC is available as a web portal, providing a valuable resource for discovery of cancer genes.
Systematic perturbation screens provide comprehensive resources for the elucidation of cancer driver genes. The perturbation of many genes in relatively few cell lines in such functional screens necessitates the development of specialized computational tools with sufficient statistical power. Here we developed APSiC (Analysis of Perturbation Screens for identifying novel Cancer genes) to identify genetic drivers and effectors in perturbation screens even with few samples. Applying APSiC to the shRNA screen Project DRIVE, APSiC identified well-known and novel putative mutational and amplified cancer genes across all cancer types and in specific cancer types. Additionally, APSiC discovered tumor-promoting and tumor-suppressive effectors, respectively, for individual cancer types, including genes involved in cell cycle control, Wnt/beta-catenin and hippo signalling pathways. We functionally demonstrated that LRRC4B, a putative novel tumor-suppressive effector, suppresses proliferation by delaying cell cycle and modulates apoptosis in breast cancer. We demonstrate APSiC is a robust statistical framework for discovery of novel cancer genes through analysis of large-scale perturbation screens. The analysis of DRIVE using APSiC is provided as a web portal and represents a valuable resource for the discovery of novel cancer genes.
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