Deep learning improves prediction of CRISPR-Cpf1 guide RNA activity

被引:240
作者
Kim, Hui Kwon [1 ,2 ]
Min, Seonwoo [3 ]
Song, Myungjae [1 ,4 ]
Jung, Soobin [1 ,2 ]
Choi, Jae Woo [1 ,5 ]
Kim, Younggwang [1 ,2 ]
Lee, Sangeun [1 ,2 ]
Yoon, Sungroh [3 ,6 ]
Kim, Hyongbum [1 ,2 ,5 ,7 ,8 ]
机构
[1] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Brain Korea Plus Project Med Sci 21, Seoul, South Korea
[3] Seoul Natl Univ, Elect & Comp Engn, Seoul, South Korea
[4] Hanyang Univ, Grad Sch Biomed Sci & Engn, Seoul, South Korea
[5] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea
[6] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea
[7] Inst Basic Sci IBS, Ctr Nanomed, Seoul, South Korea
[8] Yonsei Univ, Yonsei IBS Inst, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
OFF-TARGET; GENOME; CPF1; SPECIFICITIES; DESIGN; SGRNAS; MICE; DNA;
D O I
10.1038/nbt.4061
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
We present two algorithms to predict the activity of AsCpf1 guide RNAs. Indel frequencies for 15,000 target sequences were used in a deep-learning framework based on a convolutional neural network to train Seq-deepCpf1. We then incorporated chromatin accessibility information to create the better-performing DeepCpf1 algorithm for cell lines for which such information is available and show that both algorithms outperform previous machine learning algorithms on our own and published data sets.
引用
收藏
页码:239 / +
页数:6
相关论文
共 29 条
[1]   Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning [J].
Alipanahi, Babak ;
Delong, Andrew ;
Weirauch, Matthew T. ;
Frey, Brendan J. .
NATURE BIOTECHNOLOGY, 2015, 33 (08) :831-+
[2]  
[Anonymous], 2010, P PYTH SCI C
[3]   sgRNA Scorer 2.0: A Species-Independent Model To Predict CRISPR/Cas9 Activity [J].
Chari, Raj ;
Yeo, Nan Cher ;
Chavez, Alejandro ;
Church, George M. .
ACS SYNTHETIC BIOLOGY, 2017, 6 (05) :902-904
[4]  
Chari R, 2015, NAT METHODS, V12, P823, DOI [10.1038/NMETH.3473, 10.1038/nmeth.3473]
[5]   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-+
[6]   Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation [J].
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. .
NATURE BIOTECHNOLOGY, 2014, 32 (12) :1262-U130
[7]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[8]  
Goodfellow I, 2016, ADAPT COMPUT MACH LE, P1
[9]   Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR [J].
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 .
GENOME BIOLOGY, 2016, 17
[10]   Targeted mutagenesis in mice by electroporation of Cpf1 ribonucleoproteins [J].
Hur, Junho K. ;
Kim, Kyoungmi ;
Been, Kyung Wook ;
Baek, Gayoung ;
Ye, Sunghyeok ;
Hur, Junseok W. ;
Ryu, Seuk-Min ;
Lee, Youn Su ;
Kim, Jin-Soo .
NATURE BIOTECHNOLOGY, 2016, 34 (08) :807-808