Integrating genome-wide CRISPR screens and in silico drug profiling for targeted antidote development

Bei Wang, Yu Xu, Arabella H. Wan, Guohui Wan, Qiao-Ping Wang

Published: 2024-05-29 DOI: 10.1038/s41596-024-00995-z

genome-wide

CRISPR screens

antidote development

drug profiling

targeted therapy

AI 解读

Supplementary information

Reporting Summary

Supplementary Data 1

Scripts and example files for the virtual screen

In vitro reconstitution of COPII vesicles fromArabidopsis thalianasuspension-cultured cells

Anaerobic cryoEM protocols for air-sensitive nitrogenase proteins

Monomicellar assembly to synthesize structured and functional mesoporous carbonaceous nanomaterials

An optimized culture system for efficient derivation of porcine expanded potential stem cells from preimplantation embryos and by reprogramming somatic cells

Measuring DNA modifications with the comet assay: a compendium of protocols

Design and build of small-scale magnetic soft-bodied robots with multimodal locomotion

A practical guide to scanning light-field microscopy with digital adaptive optics

Reproducible mass spectrometry data processing and compound annotation in MZmine 3

Genetic in vivo engineering of human T lymphocytes in mouse models

Digital postprocessing and image segmentation for objective analysis of colorimetric reactions

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Lau, M.-T. et al. Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote. Nat. Commun. 10, 1655 (2019).
Wang, B. et al. Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity. Nat. Commun. 14, 2241 (2023).
Joung, J. et al. Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening. Nat. Protoc. 12, 828–863 (2017).
Lau, M.-T. et al. Systematic functional identification of cancer multi-drug resistance genes. Genome Biol. 21, 27 (2020).
Wei, L. et al. Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC. Nat. Commun. 10, 4681 (2019).
Reczek, C. R. et al. A CRISPR screen identifies a pathway required for paraquat-induced cell death. Nat. Chem. Biol. 13, 1274–1279 (2017).
Zhu, Q. et al. AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma. Signal Transduct. Target. Ther. 6, 299 (2021).
Behan, F. M. et al. Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature 568, 511–516 (2019).
Li, B. et al. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. Nat. Commun. 11, 164 (2020).
Wang, B. et al. The application of genome-wide CRISPR-Cas9 screens to dissect the molecular mechanisms of toxins. Comput. Struct. Biotechnol. J. 20, 5076–5084 (2022).
Xu, Y. et al. CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor. Nature 610, 349–355 (2022).
Li, X. et al. Paeniclostridium sordellii hemorrhagic toxin targets TMPRSS2 to induce colonic epithelial lesions. Nat. Commun. 13, 4331 (2022).
Kitchen, D. B., Decornez, H., Furr, J. R. & Bajorath, J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug Discov. 3, 935–949 (2004).
Baeshen, N. A. et al. In silico screening of some compounds derived from the desert medicinal plant Rhazya stricta for the potential treatment of COVID-19. Sci. Rep. 12, 11120 (2022).
Rodrigues, D. F. et al. In vitro mechanistic studies on α-amanitin and its putative antidotes. Arch. Toxicol. 94, 2061–2078 (2020).
Arici, M. A. et al. Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice. Hum. Exp. Toxicol. 39, 328–337 (2020).
Shortt, K. et al. Identification of novel regulatory genes in APAP induced hepatocyte toxicity by a genome-wide CRISPR-Cas9 screen. Sci. Rep. 9, 1396 (2019).
Xiong, X. et al. Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors. Cell 185, 1157–1171.e22 (2022).
Lee, H. et al. Recognition of semaphorin proteins by P. sordellii lethal toxin reveals principles of receptor specificity in clostridial toxins. Cell 182, 345–356.e16 (2020).
Daniloski, Z. et al. Identification of required host factors for SARS-CoV-2 infection in human cells. Cell 184, 92–105.e16 (2021).
Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84–87 (2014).
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).
Liu, G., Zhang, Y. & Zhang, T. Computational approaches for effective CRISPR guide RNA design and evaluation. Comput. Struct. Biotechnol. J. 18, 35–44 (2020).
Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014).
König, R. et al. A probability-based approach for the analysis of large-scale RNAi screens. Nat. Methods 4, 847–849 (2007).
O’Boyle, N. M. et al. Open Babel: an open chemical toolbox. J. Cheminform. 3, 33 (2011).
Morris, G. M. et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785–2791 (2009).
Koes, D. R., Baumgartner, M. P. & Camacho, C. J. Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise. J. Chem. Inf. Model. 53, 1893–1904 (2013).
Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455–461 (2010).
Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and Python bindings. J. Chem. Inf. Model. 61, 3891–3898 (2021).
Sanson, K. R. et al. Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities. Nat. Commun. 9, 5416 (2018).
Sherman, B. T. et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 50, W216–W221 (2022).
Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).
Liao, Y., Wang, J., Jaehnig, E. J., Shi, Z. & Zhang, B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 47, W199–W205 (2019).
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
Irwin, J. J. et al. ZINC20—a free ultralarge-scale chemical database for ligand discovery. J. Chem. Inf. Model. 60, 6065–6073 (2020).
Wishart, D. S. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 46, D1074–D1082 (2018).
Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).
Durrant, J. D. & McCammon, J. A. NNScore 2.0: a neural-network receptor-ligand scoring function. J. Chem. Inf. Model. 51, 2897–2903 (2011).
Kim, S. et al. PubChem 2023 update. Nucleic Acids Res. 51, D1373–D1380 (2023).
Volkamer, A., Kuhn, D., Rippmann, F. & Rarey, M. DoGSiteScorer: a web server for automatic binding site prediction, analysis and druggability assessment. Bioinformatics 28, 2074–2075 (2012).
Jiménez, J., Doerr, S., Martínez-Rosell, G., Rose, A. S. & De Fabritiis, G. DeepSite: protein-binding site predictor using 3D-convolutional neural networks. Bioinformatics 33, 3036–3042 (2017).
Yu, J., Zhou, Y., Tanaka, I. & Yao, M. Roll: a new algorithm for the detection of protein pockets and cavities with a rolling probe sphere. Bioinformatics 26, 46–52 (2010).

Integrating genome-wide CRISPR screens and in silico drug profiling for targeted antidote development

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