The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. ![]() ![]() Measuring error rates in genomic perturbation screens: gold standards for human functional genomics. Hart, T., Brown, K.R., Sircoulomb, F., Rottapel, R. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. The Drug Repurposing Hub: a next-generation drug library and information resource. Cornerstones of CRISPR–Cas in drug discovery and therapy. Gene essentiality profiling reveals gene networks and synthetic lethal interactions with oncogenic Ras. A CRISPR dropout screen identifies genetic vulnerabilities and therapeutic targets in acute myeloid leukemia. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Essential gene profiles in breast, pancreatic, and ovarian cancer cells. Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. CRISPR screens provide a comprehensive assessment of cancer vulnerabilities but generate false-positive hits for highly amplified genomic regions. Genomic copy number dictates a gene-independent cell response to CRISPR/Cas9 targeting. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Identification and characterization of essential genes in the human genome. We further demonstrate the utility of this collection of screens, after CERES correction, for identifying cancer-type-specific vulnerabilities. We found that CERES decreased false-positive results and estimated sgRNA activity for both this data set and previously published screens performed with different sgRNA libraries. In our efforts to define a cancer dependency map, we performed genome-scale CRISPR–Cas9 essentiality screens across 342 cancer cell lines and applied CERES to this data set. We developed CERES, a computational method to estimate gene-dependency levels from CRISPR–Cas9 essentiality screens while accounting for the copy number–specific effect. However, previous studies have reported that a gene-independent antiproliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, thereby leading to false-positive results in copy number–amplified regions 3, 4. The CRISPR–Cas9 system has revolutionized gene editing both at single genes and in multiplexed loss-of-function screens, thus enabling precise genome-scale identification of genes essential for proliferation and survival of cancer cells 1, 2. Nature Genetics volume 49, pages 1779–1784 ( 2017) Cite this article ![]() Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |