DeepCRISPR: optimized CRISPR guide RNA design by deep learning

被引：269

作者：

Chuai, Guohui ^{[1
,2
]}

Ma, Hanhui ^{[5
]}

Yan, Jifang ^{[1
,2
]}

Chen, Ming ^{[4
]}

Hong, Nanfang ^{[1
,2
]}

Xue, Dongyu ^{[1
,2
]}

Zhou, Chi ^{[1
,2
]}

Zhu, Chenyu ^{[1
,2
]}

Chen, Ke ^{[1
,2
]}

Duan, Bin ^{[1
,2
]}

Gu, Feng ^{[6
,7
,8
]}

Qu, Sheng ^{[1
,2
]}

Huang, Deshuang ^{[3
]}

Wei, Jia ^{[4
]}

Liu, Qi ^{[1
,2
]}

机构：

[1] Tongji Univ, Dept Endocrinol & Metab, Shanghai Peoples Hosp 10, Shanghai 20009, Peoples R China

[2] Tongji Univ, Sch Life Sci & Technol, Bioinformat Dept, Shanghai 20009, Peoples R China

[3] Tongji Univ, Sch Elect & Informat Engn, Machine Learning & Syst Biol Lab, Shanghai 201804, Peoples R China

[4] AstraZeneca, Innovat Ctr China, R&D Informat, 199 Liangjing Rd, Shanghai 201203, Peoples R China

[5] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

[6] Wenzhou Med Univ, State Key Lab Cultivat Base, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China

[7] Wenzhou Med Univ, Key Lab Vis Sci, Minist Hlth, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China

[8] Wenzhou Med Univ, Zhejiang Prov Key Lab Ophthalmol & Optometry, Sch Ophthalmol & Optometry, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China

来源：

GENOME BIOLOGY | 2018年 / 19卷

基金：

中国国家自然科学基金;

关键词：

CRISPR system; Gene knockout; Deep learning; On-targets; Off-targets; OFF-TARGET CLEAVAGE; GENOME; SEQ; DNA; SPECIFICITIES; PREDICTION; NUCLEASES; SELECTION; SGRNAS;

D O I：

10.1186/s13059-018-1459-4

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A major challenge for effective application of CRISPR systems is to accurately predict the single guide RNA (sgRNA) on-target knockout efficacy and off-target profile, which would facilitate the optimized design of sgRNAs with high sensitivity and specificity. Here we present DeepCRISPR, a comprehensive computational platform to unify sgRNA on-target and off-target site prediction into one framework with deep learning, surpassing available state-of-the-art in silico tools. In addition, DeepCRISPR fully automates the identification of sequence and epigenetic features that may affect sgRNA knockout efficacy in a data-driven manner. DeepCRISPR is available at http://www.deeperispr.net/.

引用

页数：18

共 55 条

[11] Chuai G, 2018, DEEPCRISPR OPTIMIZED
[12] In Silico Meets In Vivo: Towarcs Computational CRISPR-Based sgRNA Design
Chuai, Guo-hui
Wang, Qi-Long
Liu, Qi
[J]. TRENDS IN BIOTECHNOLOGY, 2017, 35 (01) : 12 - 21
[13] Multiplex Genome Engineering Using CRISPR/Cas Systems
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
[J]. SCIENCE, 2013, 339 (6121) : 819 - 823
[14] Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9
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.
[J]. NATURE BIOTECHNOLOGY, 2016, 34 (02) : 184 - +
[15] Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation
Doench, John G.
Hartenian, Ella
Graham, Daniel B.
Tothova, Zuzana
Hegde, Mudra
Smith, Ian
Sullender, Meagan
Ebert, Benjamin L.
Xavier, Ramnik J.
Root, David E.
[J]. NATURE BIOTECHNOLOGY, 2014, 32 (12) : 1262 - U130
[16] The new frontier of genome engineering with CRISPR-Cas9
Doudna, Jennifer A.
Charpentier, Emmanuelle
[J]. SCIENCE, 2014, 346 (6213) : 1077 - +
[17] The ENCODE (ENCyclopedia of DNA elements) Project
Feingold, EA
Good, PJ
Guyer, MS
Kamholz, S
Liefer, L
Wetterstrand, K
Collins, FS
Gingeras, TR
Kampa, D
Sekinger, EA
Cheng, J
Hirsch, H
Ghosh, S
Zhu, Z
Pate, S
Piccolboni, A
Yang, A
Tammana, H
Bekiranov, S
Kapranov, P
Harrison, R
Church, G
Struhl, K
Ren, B
Kim, TH
Barrera, LO
Qu, C
Van Calcar, S
Luna, R
Glass, CK
Rosenfeld, MG
Guigo, R
Antonarakis, SE
Birney, E
Brent, M
Pachter, L
Reymond, A
Dermitzakis, ET
Dewey, C
Keefe, D
Denoeud, F
Lagarde, J
Ashurst, J
Hubbard, T
Wesselink, JJ
Castelo, R
Eyras, E
Myers, RM
Sidow, A
Batzoglou, S
[J]. SCIENCE, 2004, 306 (5696) : 636 - 640
[18] Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases
Frock, Richard L.
Hu, Jiazhi
Meyers, Robin M.
Ho, Yu-Jui
Kii, Erina
Alt, Frederick W.
[J]. NATURE BIOTECHNOLOGY, 2015, 33 (02) : 179 - 186
[19] High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
Fu, Yanfang
Foden, Jennifer A.
Khayter, Cyd
Maeder, Morgan L.
Reyon, Deepak
Joung, J. Keith
Sander, Jeffry D.
[J]. NATURE BIOTECHNOLOGY, 2013, 31 (09) : 822 - +
[20] Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR
Haeussler, Maximilian
Schoenig, Kai
Eckert, Helene
Eschstruth, Alexis
Mianne, Joffrey
Renaud, Jean-Baptiste
Schneider-Maunoury, Sylvie
Shkumatava, Alena
Teboul, Lydia
Kent, Jim
Joly, Jean-Stephane
Concordet, Jean-Paul
[J]. GENOME BIOLOGY, 2016, 17

← 1 2 3 4 5 6 →