An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens

被引:4
作者
Vinceti, Alessandro [1 ]
De Lucia, Riccardo Roberto [1 ]
Cremaschi, Paolo [1 ]
Perron, Umberto [1 ]
Karakoc, Emre [2 ]
Mauri, Luca [3 ]
Fernandez, Carlos [3 ]
Kluczynski, Krzysztof Henryk [3 ]
Anderson, Daniel Stephen [3 ]
Iorio, Francesco [1 ,2 ]
机构
[1] Human Technopole, Computat Biol Res Ctr, Viale Rita Levi Montalcini 1, I-20157 Milan, Italy
[2] Wellcome Sanger Inst, Canc Dependency Map Analyt, Wellcome Genome Campus, Cambridge CB10 1SA, England
[3] Human Technopole, ICT & Digitalisat, Viale Rita Levi Montalcini 1, I-20157 Milan, Italy
来源
CELL REPORTS METHODS | 2023年 / 3卷 / 01期
关键词
CIRCULAR BINARY SEGMENTATION; CANCER; VULNERABILITIES; EXPRESSION; DESIGN; REPAIR; CELLS; SET;
D O I
10.1016/j.crmeth.2022.100373
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals while maintaining sensitivity in identifying relevant genetic dependencies. Here, we present CRISPRcleanRWebApp, a web application enabling access to CRISPRcleanR through an intuitive interface. CRISPRcleanRWebApp removes the complexity of R/python language user interactions; provides user-friendly access to a complete analytical pipeline, not requiring any data pre-processing and generating gene-level sum-maries of essentiality with associated statistical scores; and offers a range of interactively explorable plots while supporting a more comprehensive range of CRISPR guide RNAs' libraries than the original package. CRISPRcleanRWebApp is available at https://crisprcleanr-webapp.fht.org/.
引用
收藏
页数:17
相关论文
共 48 条
[1]   Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting [J].
Aguirre, Andrew J. ;
Meyers, Robin M. ;
Weir, Barbara A. ;
Vazquez, Francisca ;
Zhang, Cheng-Zhong ;
Ben-David, Uri ;
Cook, April ;
Ha, Gavin ;
Harrington, William F. ;
Doshi, Mihir B. ;
Kost-Alimova, Maria ;
Gill, Stanley ;
Xu, Han ;
Ali, Levi D. ;
Jiang, Guozhi ;
Pantel, Sasha ;
Lee, Yenarae ;
Goodale, Amy ;
Cherniack, Andrew D. ;
Oh, Coyin ;
Kryukov, Gregory ;
Cowley, Glenn S. ;
Garraway, Levi A. ;
Stegmaier, Kimberly ;
Roberts, Charles W. ;
Golub, Todd R. ;
Meyerson, Matthew ;
Root, David E. ;
Tsherniak, Aviad ;
Hahn, William C. .
CANCER DISCOVERY, 2016, 6 (08) :914-929
[2]   The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].
Barretina, Jordi ;
Caponigro, Giordano ;
Stransky, Nicolas ;
Venkatesan, Kavitha ;
Margolin, Adam A. ;
Kim, Sungjoon ;
Wilson, Christopher J. ;
Lehar, Joseph ;
Kryukov, Gregory V. ;
Sonkin, Dmitriy ;
Reddy, Anupama ;
Liu, Manway ;
Murray, Lauren ;
Berger, Michael F. ;
Monahan, John E. ;
Morais, Paula ;
Meltzer, Jodi ;
Korejwa, Adam ;
Jane-Valbuena, Judit ;
Mapa, Felipa A. ;
Thibault, Joseph ;
Bric-Furlong, Eva ;
Raman, Pichai ;
Shipway, Aaron ;
Engels, Ingo H. ;
Cheng, Jill ;
Yu, Guoying K. ;
Yu, Jianjun ;
Aspesi, Peter, Jr. ;
de Silva, Melanie ;
Jagtap, Kalpana ;
Jones, Michael D. ;
Wang, Li ;
Hatton, Charles ;
Palescandolo, Emanuele ;
Gupta, Supriya ;
Mahan, Scott ;
Sougnez, Carrie ;
Onofrio, Robert C. ;
Liefeld, Ted ;
MacConaill, Laura ;
Winckler, Wendy ;
Reich, Michael ;
Li, Nanxin ;
Mesirov, Jill P. ;
Gabriel, Stacey B. ;
Getz, Gad ;
Ardlie, Kristin ;
Chan, Vivien ;
Myer, Vic E. .
NATURE, 2012, 483 (7391) :603-607
[3]   Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens [J].
Behan, Fiona M. ;
Iorio, Francesco ;
Picco, Gabriele ;
Goncalves, Emanuel ;
Beaver, Charlotte M. ;
Migliardi, Giorgia ;
Santos, Rita ;
Rao, Yanhua ;
Sassi, Francesco ;
Pinnelli, Marika ;
Ansari, Rizwan ;
Harper, Sarah ;
Jackson, David Adam ;
Mcrae, Rebecca ;
Pooley, Rachel ;
Wilkinson, Piers ;
van der Meer, Dieudonne ;
Dow, David ;
Buser-Doepner, Carolyn ;
Bertotti, Andrea ;
Trusolino, Livio ;
Stronach, Euan A. ;
Saez-Rodriguez, Julio ;
Yusa, Kosuke ;
Garnett, Mathew J. .
NATURE, 2019, 568 (7753) :511-+
[4]   Multiplex Genome Engineering Using CRISPR/Cas Systems [J].
Cong, Le ;
Ran, F. Ann ;
Cox, David ;
Lin, Shuailiang ;
Barretto, Robert ;
Habib, Naomi ;
Hsu, Patrick D. ;
Wu, Xuebing ;
Jiang, Wenyan ;
Marraffini, Luciano A. ;
Zhang, Feng .
SCIENCE, 2013, 339 (6121) :819-823
[5]   DNA double strand break repair via non-homologous end-joining [J].
Davis, Anthony J. ;
Chen, David J. .
TRANSLATIONAL CANCER RESEARCH, 2013, 2 (03) :130-143
[6]   Correction of copy number induced false positives in CRISPR screens [J].
de Weck, Antoine ;
Golji, Javad ;
Jones, Michael D. ;
Korn, Joshua M. ;
Billy, Eric ;
McDonald, E. Robert, III ;
Schmelzie, Tobias ;
Bitter, Hans ;
Kauffmann, Audrey .
PLOS COMPUTATIONAL BIOLOGY, 2018, 14 (07)
[7]  
Dempster JM., 2019, Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines p, P720243, DOI [10.1101/720243, DOI 10.1101/720243]
[8]  
Dempster JM., 2021, BIORXIV, V25, DOI [DOI 10.1101/2021.02.25.432728, 10.1101/2021.02.25.432728]
[9]   Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets [J].
Dempster, Joshua M. ;
Pacini, Clare ;
Pantel, Sasha ;
Behan, Fiona M. ;
Green, Thomas ;
Krill-Burger, John ;
Beaver, Charlotte M. ;
Younger, Scott T. ;
Zhivich, Victor ;
Najgebauer, Hanna ;
Allen, Felicity ;
Goncalves, Emanuel ;
Shepherd, Rebecca ;
Doench, John G. ;
Yusa, Kosuke ;
Vazquez, Francisca ;
Parts, Leopold ;
Boehm, Jesse S. ;
Golub, Todd R. ;
Hahn, William C. ;
Root, David E. ;
Garnett, Mathew J. ;
Tsherniak, Aviad ;
Iorio, Francesco .
NATURE COMMUNICATIONS, 2019, 10 (1)
[10]   Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 [J].
Doench, John G. ;
Fusi, Nicolo ;
Sullender, Meagan ;
Hegde, Mudra ;
Vaimberg, Emma W. ;
Donovan, Katherine F. ;
Smith, Ian ;
Tothova, Zuzana ;
Wilen, Craig ;
Orchard, Robert ;
Virgin, Herbert W. ;
Listgarten, Jennifer ;
Root, David E. .
NATURE BIOTECHNOLOGY, 2016, 34 (02) :184-+