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      DeepCRISPR: optimized CRISPR guide RNA design by deep learning

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          Abstract

          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.deepcrispr.net/.

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          The online version of this article (10.1186/s13059-018-1459-4) contains supplementary material, which is available to authorized users.

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          Most cited references20

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          Deep Learning in Neural Networks: An Overview

          (2014)
          In recent years, deep artificial neural networks (including recurrent ones) have won numerous contests in pattern recognition and machine learning. This historical survey compactly summarises relevant work, much of it from the previous millennium. Shallow and deep learners are distinguished by the depth of their credit assignment paths, which are chains of possibly learnable, causal links between actions and effects. I review deep supervised learning (also recapitulating the history of backpropagation), unsupervised learning, reinforcement learning & evolutionary computation, and indirect search for short programs encoding deep and large networks.
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            Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach

            We develop an in vivo library-on-library methodology to simultaneously assess single guide RNA (sgRNA) activity across ~1,400 genomic loci. Assaying across multiple human cell types, end-processing enzymes, and two Cas9 orthologs, we unravel underlying nucleotide sequence and epigenetic parameters. Our results enable improved design of reagents, shed light on mechanisms of genome targeting, and provide a generalizable framework to study nucleic acid-nucleic acid interactions and biochemistry in high throughput.
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              Cas-Designer: a web-based tool for choice of CRISPR-Cas9 target sites.

              We present Cas-Designer, a user-friendly program to aid researchers in choosing appropriate target sites in a gene of interest for type II CRISPR/Cas-derived RNA-guided endonucleases, which are now widely used for biomedical research and biotechnology. Cas-Designer rapidly provides the list of all possible guide RNA sequences in a given input DNA sequence and their potential off-target sites including bulge-type sites in a genome of choice. In addition, the program assigns an out-of-frame score to each target site to help users choose appropriate sites for gene knockout. Cas-Designer shows the results in an interactive table and provides user-friendly filter functions.
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                Author and article information

                Contributors
                dshuang@tongji.edu.cn
                Jenny.Wei@astrazeneca.com
                qiliu@tongji.edu.cn
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                26 June 2018
                26 June 2018
                2018
                : 19
                : 80
                Affiliations
                [1 ]ISNI 0000 0004 0527 0050, GRID grid.412538.9, Department of Endocrinology & Metabolism, , Shanghai Tenth People’s Hospital, Tongji University, ; Shanghai, 20009 China
                [2 ]ISNI 0000000123704535, GRID grid.24516.34, Bioinformatics Department, , School of Life Sciences and Technology, Tongji University, ; Shanghai, 20009 China
                [3 ]ISNI 0000000123704535, GRID grid.24516.34, Machine Learning & Systems Biology Lab, School of Electronics and Information Engineering, , Tongji University, ; Shanghai, 201804 China
                [4 ]R&D Information, Innovation Center China, AstraZeneca, 199 Liangjing Road, Shanghai, 201203 China
                [5 ]GRID grid.440637.2, School of Life Science and Technology, , ShanghaiTech University, ; Shanghai, China
                [6 ]ISNI 0000 0001 0348 3990, GRID grid.268099.c, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, , School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, ; Wenzhou, Zhejiang, 325027 China
                Article
                1459
                10.1186/s13059-018-1459-4
                6020378
                29945655
                42f4396e-78f2-460f-8a24-ee2d63f70261
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 January 2018
                : 28 May 2018
                Categories
                Method
                Custom metadata
                © The Author(s) 2018

                Genetics
                crispr system,gene knockout,deep learning,on-targets,off-targets
                Genetics
                crispr system, gene knockout, deep learning, on-targets, off-targets

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