当前位置： SCI文献检索 > Nature Communications期刊下所有文献 > Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning.

Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning.

Abstract：

:Highly specific Cas9 nucleases derived from SpCas9 are valuable tools for genome editing, but their wide applications are hampered by a lack of knowledge governing guide RNA (gRNA) activity. Here, we perform a genome-scale screen to measure gRNA activity for two highly specific SpCas9 variants (eSpCas9(1.1) and SpCas9-HF1) and wild-type SpCas9 (WT-SpCas9) in human cells, and obtain indel rates of over 50,000 gRNAs for each nuclease, covering ~20,000 genes. We evaluate the contribution of 1,031 features to gRNA activity and develope models for activity prediction. Our data reveals that a combination of RNN with important biological features outperforms other models for activity prediction. We further demonstrate that our model outperforms other popular gRNA design tools. Finally, we develop an online design tool DeepHF for the three Cas9 nucleases. The database, as well as the designer tool, is freely accessible via a web server, http://www.DeepHF.com/ .

journal_name

Nat Commun

journal_title

Nature communications

authors

Wang D,Zhang C,Wang B,Li B,Wang Q,Liu D,Wang H,Zhou Y,Shi L,Lan F,Wang Y

doi

10.1038/s41467-019-12281-8

subject

Has Abstract

pub_date

2019-09-19 00:00:00

pages

4284

issue

1

issn

2041-1723

pii

10.1038/s41467-019-12281-8

journal_volume

10

pub_type

杂志文章

相关文献

Nature Communications文献大全
  • Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis.

    abstract：:Stimulation of TNFR1 by TNFα can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFα-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulati...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-017-00406-w

    authors： Geng J,Ito Y,Shi L,Amin P,Chu J,Ouchida AT,Mookhtiar AK,Zhao H,Xu D,Shan B,Najafov A,Gao G,Akira S,Yuan J

    更新日期：2017-08-25 00:00:00

  • Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons.

    abstract：:Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dyna...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-15287-9

    authors： Negrete-Hurtado A,Overhoff M,Bera S,De Bruyckere E,Schätzmüller K,Kye MJ,Qin C,Lammers M,Kondylis V,Neundorf I,Kononenko NL

    更新日期：2020-03-24 00:00:00

  • Molecular basis for RNA polymerase-dependent transcription complex recycling by the helicase-like motor protein HelD.

    abstract：:In bacteria, transcription complexes stalled on DNA represent a major source of roadblocks for the DNA replication machinery that must be removed in order to prevent damaging collisions. Gram-positive bacteria contain a transcription factor HelD that is able to remove and recycle stalled complexes, but it was not know...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-20157-5

    authors： Newing TP,Oakley AJ,Miller M,Dawson CJ,Brown SHJ,Bouwer JC,Tolun G,Lewis PJ

    更新日期：2020-12-18 00:00:00

  • Full-field implementation of a perfect eavesdropper on a quantum cryptography system.

    abstract：:Quantum key distribution (QKD) allows two remote parties to grow a shared secret key. Its security is founded on the principles of quantum mechanics, but in reality it significantly relies on the physical implementation. Technological imperfections of QKD systems have been previously explored, but no attack on an esta...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms1348

    authors： Gerhardt I,Liu Q,Lamas-Linares A,Skaar J,Kurtsiefer C,Makarov V

    更新日期：2011-06-14 00:00:00

  • CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair.

    abstract：:In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integrat...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03475-7

    authors： Charpentier M,Khedher AHY,Menoret S,Brion A,Lamribet K,Dardillac E,Boix C,Perrouault L,Tesson L,Geny S,De Cian A,Itier JM,Anegon I,Lopez B,Giovannangeli C,Concordet JP

    更新日期：2018-03-19 00:00:00

  • Flexible and ultra-lightweight polymer membrane lasers.

    abstract：:Organic semiconductors enable the fabrication of a range of lightweight and mechanically flexible optoelectronic devices. Most organic semiconductor lasers, however, have remained rigid until now, predominantly due to the need for a support substrate. Here, we use a simple fabrication process to make membrane-based, s...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03874-w

    authors： Karl M,Glackin JME,Schubert M,Kronenberg NM,Turnbull GA,Samuel IDW,Gather MC

    更新日期：2018-05-01 00:00:00

  • Synthesis of tetrasubstituted 1-silyloxy-3-aminobutadienes and chemistry beyond Diels-Alder reactions.

    abstract：:Electron-rich dienes have revolutionized the synthesis of complex compounds since the discovery of the legendary Diels-Alder cycloaddition reaction. This highly efficient bond-forming process has served as a fundamental strategy to assemble many structurally formidable molecules. Amino silyloxy butadienes are arguably...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms7913

    authors： Li X,Peng S,Li L,Huang Y

    更新日期：2015-04-21 00:00:00

  • Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.

    abstract：:Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-de...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-07824-4

    authors： Gannon HS,Zou T,Kiessling MK,Gao GF,Cai D,Choi PS,Ivan AP,Buchumenski I,Berger AC,Goldstein JT,Cherniack AD,Vazquez F,Tsherniak A,Levanon EY,Hahn WC,Meyerson M

    更新日期：2018-12-21 00:00:00

  • Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings.

    abstract：:The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detecto...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-04549-2

    authors： Gliske SV,Irwin ZT,Chestek C,Hegeman GL,Brinkmann B,Sagher O,Garton HJL,Worrell GA,Stacey WC

    更新日期：2018-06-01 00:00:00

  • Electropolymerization on wireless electrodes towards conducting polymer microfibre networks.

    abstract：:Conducting polymers can be easily obtained by electrochemical oxidation of aromatic monomers on an electrode surface as a film state. To prepare conducting polymer fibres by electropolymerization, templates such as porous membranes are necessary in the conventional methods. Here we report the electropolymerization of ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms10404

    authors： Koizumi Y,Shida N,Ohira M,Nishiyama H,Tomita I,Inagi S

    更新日期：2016-01-25 00:00:00

  • Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy.

    abstract：:Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more suscep...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms14754

    authors： Liu Z,Ravindranathan R,Kalinski P,Guo ZS,Bartlett DL

    更新日期：2017-03-27 00:00:00

  • Vibrational couplings and energy transfer pathways of water's bending mode.

    abstract：:Coupling between vibrational modes is essential for energy transfer and dissipation in condensed matter. For water, different O-H stretch modes are known to be very strongly coupled both within and between water molecules, leading to ultrafast dissipation and delocalization of vibrational energy. In contrast, the info...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-19759-w

    authors： Yu CC,Chiang KY,Okuno M,Seki T,Ohto T,Yu X,Korepanov V,Hamaguchi HO,Bonn M,Hunger J,Nagata Y

    更新日期：2020-11-25 00:00:00

  • Examining charitable giving in real-world online donations.

    abstract：:The current study uses big data to study prosocial behavior by analyzing donations made on the GoFundMe platform. In a dataset of more than $44 million in online donations, we find that 21% were made while opting to be anonymous to the public, with survey results indicating that 11% of these anonymous donations (2.3% ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-11852-z

    authors： Sisco MR,Weber EU

    更新日期：2019-09-03 00:00:00

  • Fuelling conditions at staging sites can mitigate Arctic warming effects in a migratory bird.

    abstract：:Under climate warming, migratory birds should align reproduction dates with advancing plant and arthropod phenology. To arrive on the breeding grounds earlier, migrants may speed up spring migration by curtailing the time spent en route, possibly at the cost of decreased survival rates. Based on a decades-long series ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-06673-5

    authors： Rakhimberdiev E,Duijns S,Karagicheva J,Camphuysen CJ,VRS Castricum.,Dekinga A,Dekker R,Gavrilov A,Ten Horn J,Jukema J,Saveliev A,Soloviev M,Tibbitts TL,van Gils JA,Piersma T

    更新日期：2018-10-15 00:00:00

  • Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

    abstract：:Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characte...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-14457-z

    authors： Cuomo ASE,Seaton DD,McCarthy DJ,Martinez I,Bonder MJ,Garcia-Bernardo J,Amatya S,Madrigal P,Isaacson A,Buettner F,Knights A,Natarajan KN,HipSci Consortium.,Vallier L,Marioni JC,Chhatriwala M,Stegle O

    更新日期：2020-02-10 00:00:00

  • Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

    abstract：:Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aimi...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms9111

    authors： Huang J,Howie B,McCarthy S,Memari Y,Walter K,Min JL,Danecek P,Malerba G,Trabetti E,Zheng HF,UK10K Consortium.,Gambaro G,Richards JB,Durbin R,Timpson NJ,Marchini J,Soranzo N

    更新日期：2015-09-14 00:00:00

  • Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density.

    abstract：:Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered genetic signals robustly associated with bone mineral density (BMD), but not the precise localization of effector genes. Here, we carry out physical and direct variant to gene mapping in human mesenchymal progenitor cell-de...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-09302-x

    authors： Chesi A,Wagley Y,Johnson ME,Manduchi E,Su C,Lu S,Leonard ME,Hodge KM,Pippin JA,Hankenson KD,Wells AD,Grant SFA

    更新日期：2019-03-19 00:00:00

  • Solar energy storage at an atomically defined organic-oxide hybrid interface.

    abstract：:Molecular photoswitches provide an extremely simple solution for solar energy conversion and storage. To convert stored energy to electricity, however, the photoswitch has to be coupled to a semiconducting electrode. In this work, we report on the assembly of an operational solar-energy-storing organic-oxide hybrid in...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-10263-4

    authors： Schuschke C,Hohner C,Jevric M,Ugleholdt Petersen A,Wang Z,Schwarz M,Kettner M,Waidhas F,Fromm L,Sumby CJ,Görling A,Brummel O,Moth-Poulsen K,Libuda J

    更新日期：2019-06-03 00:00:00

  • Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents.

    abstract：:Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to tr...

    journal_title：Nature communications

    pub_type： 杂志文章,多中心研究

    doi：10.1038/ncomms14140

    authors： Büchel C,Peters J,Banaschewski T,Bokde AL,Bromberg U,Conrod PJ,Flor H,Papadopoulos D,Garavan H,Gowland P,Heinz A,Walter H,Ittermann B,Mann K,Martinot JL,Paillère-Martinot ML,Nees F,Paus T,Pausova Z,Poustka L,Riets

    更新日期：2017-02-21 00:00:00

  • O2 evolution and recovery of the water-oxidizing enzyme.

    abstract：:In photosystem II, light-induced water oxidation occurs at the Mn4CaO5 cluster. Here we demonstrate proton releases, dioxygen formation, and substrate water incorporation in response to Mn4CaO5 oxidation in the protein environment, using a quantum mechanical/molecular mechanical approach and molecular dynamics simulat...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03545-w

    authors： Kawashima K,Takaoka T,Kimura H,Saito K,Ishikita H

    更新日期：2018-03-28 00:00:00

  • BK channel inactivation gates daytime excitability in the circadian clock.

    abstract：:Inactivation is an intrinsic property of several voltage-dependent ion channels, closing the conduction pathway during membrane depolarization and dynamically regulating neuronal activity. BK K(+) channels undergo N-type inactivation via their β2 subunit, but the physiological significance is not clear. Here, we repor...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms10837

    authors： Whitt JP,Montgomery JR,Meredith AL

    更新日期：2016-03-04 00:00:00

  • Diffusion in translucent media.

    abstract：:Diffusion is the result of repeated random scattering. It governs a wide range of phenomena from Brownian motion, to heat flow through window panes, neutron flux in fuel rods, dispersion of light in human tissue, and electronic conduction. It is universally acknowledged that the diffusion approach to describing wave t...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-04242-4

    authors： Shi Z,Genack AZ

    更新日期：2018-05-10 00:00:00

  • Phototaxis of synthetic microswimmers in optical landscapes.

    abstract：:Many microorganisms, with phytoplankton and zooplankton as prominent examples, display phototactic behaviour, that is, the ability to perform directed motion within a light gradient. Here we experimentally demonstrate that sensing of light gradients can also be achieved in a system of synthetic photo-activated micropa...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms12828

    authors： Lozano C,Ten Hagen B,Löwen H,Bechinger C

    更新日期：2016-09-30 00:00:00

  • Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.

    abstract：:Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03621-1

    authors： Barbeira AN,Dickinson SP,Bonazzola R,Zheng J,Wheeler HE,Torres JM,Torstenson ES,Shah KP,Garcia T,Edwards TL,Stahl EA,Huckins LM,GTEx Consortium.,Nicolae DL,Cox NJ,Im HK

    更新日期：2018-05-08 00:00:00

  • Weakening of the stratospheric polar vortex by Arctic sea-ice loss.

    abstract：:Successive cold winters of severely low temperatures in recent years have had critical social and economic impacts on the mid-latitude continents in the Northern Hemisphere. Although these cold winters are thought to be partly driven by dramatic losses of Arctic sea-ice, the mechanism that links sea-ice loss to cold w...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5646

    authors： Kim BM,Son SW,Min SK,Jeong JH,Kim SJ,Zhang X,Shim T,Yoon JH

    更新日期：2014-09-02 00:00:00

  • REV7 is required for processing AID initiated DNA lesions in activated B cells.

    abstract：:Activation-induced cytidine deaminase (AID) initiates both antibody class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversification. DNA double-strand break response (DSBR) factors promote rearrangement in CSR, while translesion synthesis (TLS) polymerases generate mutations in SHM. REV7, ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16632-8

    authors： Yang D,Sun Y,Chen J,Zhang Y,Fan S,Huang M,Xie X,Cai Y,Shang Y,Gui T,Sun L,Hu J,Dong J,Yeap LS,Wang X,Xiao W,Meng FL

    更新日期：2020-06-04 00:00:00

  • Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome.

    abstract：:Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appea...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-15198-9

    authors： Li M,Nishio SY,Naruse C,Riddell M,Sapski S,Katsuno T,Hikita T,Mizapourshafiyi F,Smith FM,Cooper LT,Lee MG,Asano M,Boettger T,Krueger M,Wietelmann A,Graumann J,Day BW,Boyd AW,Offermanns S,Kitajiri SI,Usami SI,Nak

    更新日期：2020-03-12 00:00:00

  • PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity.

    abstract：:Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-17813-1

    authors： Helou DG,Shafiei-Jahani P,Lo R,Howard E,Hurrell BP,Galle-Treger L,Painter JD,Lewis G,Soroosh P,Sharpe AH,Akbari O

    更新日期：2020-08-10 00:00:00

  • Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin.

    abstract：:Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metal...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-18939-y

    authors： Sun H,Zhang Q,Wang R,Wang H,Wong YT,Wang M,Hao Q,Yan A,Kao RY,Ho PL,Li H

    更新日期：2020-10-16 00:00:00

  • Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans.

    abstract：:A reliable method for recording evoked synaptic events in identified neurons in Caenorhabditis elegans would greatly accelerate our understanding of its nervous system at the molecular, cellular and network levels. Here we describe a method for recording synaptic currents and potentials from identified neurons in near...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms1304

    authors： Lindsay TH,Thiele TR,Lockery SR

    更新日期：2011-01-01 00:00:00