Gorelick, A. N. et al. Phase and context shape the function of composite oncogenic mutations. Nature 582, 100–103 (2020).
Google Scholar
Hyman, D. M. et al. AKT inhibition in solid tumors with AKT1 mutations. J. Clin. Oncol. 35, 2251–2259 (2017).
Google Scholar
Vasan, N. et al. Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kalpha inhibitors. Science 366, 714–723 (2019).
Google Scholar
Zafra, M. P. et al. An in vivo Kras allelic series reveals distinct phenotypes of common oncogenic variants. Cancer Discov. 10, 1654–1671 (2020).
Google Scholar
Findlay, G. M. et al. Accurate classification of BRCA1 variants with saturation genome editing. Nature 562, 217–222 (2018).
Google Scholar
Vivanco, I. et al. Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Disco. 2, 458–471 (2012).
Google Scholar
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).
Google Scholar
Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017).
Google Scholar
Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843–846 (2018).
Google Scholar
Zafra, M. P. et al. Optimized base editors enable efficient editing in cells, organoids and mice. Nat. Biotechnol. 36, 888–893 (2018).
Google Scholar
Kleinstiver, B. P. et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481–485 (2015).
Google Scholar
Katti, A. et al. GO: a functional reporter system to identify and enrich base editing activity. Nucleic Acids Res. 48, 2841–2852 (2020).
Google Scholar
Vakulskas, C. A. et al. A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells. Nat. Med. 24, 1216–1224 (2018).
Google Scholar
Nishimasu, H. et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 361, 1259–1262 (2018).
Google Scholar
Hu, J. H. et al. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 556, 57–63 (2018).
Google Scholar
Zehir, A. et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat. Med. 23, 703–713 (2017).
Google Scholar
Chakravarty, D. et al. A precision oncology knowledge base. JCO Precis. Oncol. 2017, PO.17.00011 (2017).
Chakravarty, D. & Solit, D. B. Clinical cancer genomic profiling. Nat. Rev. Genet. 22, 483–501 (2021).
Google Scholar
Dimitrova, N. et al. Stromal expression of miR-143/145 promotes neoangiogenesis in lung cancer development. Cancer Discov. 6, 188–201 (2016).
Google Scholar
Lee, K. E. & Bar-Sagi, D. Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. Cancer Cell 18, 448–458 (2010).
Google Scholar
Arbab, M. et al. Determinants of base editing outcomes from target library analysis and machine learning. Cell 182, 463–480.e430 (2020).
Google Scholar
Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
Google Scholar
Komor, A. C. et al. Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci. Adv. 3, eaao4774 (2017).
Google Scholar
Kastenhuber, E. R. & Lowe, S. W. Putting p53 in context. Cell 170, 1062–1078 (2017).
Google Scholar
Muller, P. A. & Vousden, K. H. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell 25, 304–317 (2014).
Google Scholar
Vassilev, L. T. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844–848 (2004).
Google Scholar
Li, W. et al. Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR. Genome Biol. 16, 281 (2015).
Google Scholar
Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014).
Google Scholar
Morris, J. P. T. et al. α-Ketoglutarate links p53 to cell fate during tumour suppression. Nature 573, 595–599 (2019).
Google Scholar
Kanda, M. et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin. Gastroenterol. Hepatol. 11, 719–730 e715 (2013).
Google Scholar
Koblan, L. W. et al.Efficient C*G-to-G*C base editors developed using CRISPRi screens, target-library analysis, and machine learning. Nat. Biotechnol. 39, 1414–1425 (2021).
Google Scholar
Shen, M. W. et al. Predictable and precise template-free CRISPR editing of pathogenic variants. Nature 563, 646–651 (2018).
Google Scholar
Song, M. et al. Sequence-specific prediction of the efficiencies of adenine and cytosine base editors. Nat. Biotechnol. 38, 1037–1043 (2020).
Google Scholar
Tycko, J. et al. Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells. Nat. Commun. 9, 2962 (2018).
Google Scholar
Marquart, K. F. et al. Predicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens. Nat. Commun. 12, 5114 (2021).
Google Scholar
Chen, L. et al. Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins. Nat. Commun. 12, 1384 (2021).
Google Scholar
Kurt, I. C. et al. CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat. Biotechnol. 39, 41–46 (2021).
Google Scholar
Zhao, D. et al. Glycosylase base editors enable C-to-A and C-to-G base changes. Nat. Biotechnol. 39, 35–40 (2021).
Google Scholar
Hyman, D. M., Taylor, B. S. & Baselga, J. Implementing genome-driven oncology. Cell 168, 584–599 (2017).
Google Scholar
Cuella-Martin, R. et al. Functional interrogation of DNA damage response variants with base editing screens. Cell 184, 1081–1097 e1019 (2021).
Google Scholar
Hanna, R. E. et al. Massively parallel assessment of human variants with base editor screens. Cell 184, 1064–1080 e1020 (2021).
Google Scholar
Xu, P. Genome-wide interrogation of gene functions through base editor screens empowered by barcoded sgRNAs. Nat. Biotechnol. 39, 1403–1413 (2021).
Google Scholar
Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167, 1867–1882.e1821 (2016).
Google Scholar
Datlinger, P. et al. Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14, 297–301 (2017).
Google Scholar
Dixit, A. et al. Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167, 1853–1866.e1817 (2016).
Google Scholar
Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019).
Google Scholar
Kim, H. K. et al. Predicting the efficiency of prime editing guide RNAs in human cells. Nat. Biotechnol. 39, 198–206 (2021).
Google Scholar
Clement, K. et al. CRISPResso2 provides accurate and rapid genome editing sequence analysis. Nat. Biotechnol. 37, 224–226 (2019).
Google Scholar
Soto-Feliciano, Y. M. et al. A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition. Preprint at bioRxiv https://doi.org/10.1101/2021.10.22.465184 (2021).
Chen, B. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155, 1479–1491 (2013).
Google Scholar
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184–191 (2016).
Google Scholar

