Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06

AUTHORS

Shengdar Q Tsai, Nicolas Wyvekens, Cyd Khayter, Jennifer A Foden, Vishal Thapar, Deepak Reyon, Mathew J Goodwin, Martin J Aryee, J Keith Joung

ABSTRACT

Monomeric CRISPR-Cas9 nucleases are widely used for targeted genome editing but can induce unwanted off-target mutations with high frequencies. Here we describe dimeric RNA-guided FokI nucleases (RFNs) that can recognize extended sequences and edit endogenous genes with high efficiencies in human cells. RFN cleavage activity depends strictly on the binding of two guide RNAs (gRNAs) to DNA with a defined spacing and orientation substantially reducing the likelihood that a suitable target site will occur more than once in the genome and therefore improving specificities relative to wild-type Cas9 monomers. RFNs guided by a single gRNA generally induce lower levels of unwanted mutations than matched monomeric Cas9 nickases. In addition, we describe a simple method for expressing multiple gRNAs bearing any 5' end nucleotide, which gives dimeric RFNs a broad targeting range. RFNs combine the ease of RNA-based targeting with the specificity enhancement inherent to dimerization and are likely to be useful in applications that require highly precise genome editing. More... »

PAGES

569

References to SciGraph publications

  • 2014-04. CRISPR-Cas systems for editing, regulating and targeting genomes in NATURE BIOTECHNOLOGY
  • 2013-09. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering in NATURE BIOTECHNOLOGY
  • 2013-09. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells in NATURE BIOTECHNOLOGY
  • 2013-09. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity in NATURE BIOTECHNOLOGY
  • 2013-01. TALENs: a widely applicable technology for targeted genome editing in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2013-10. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system in CELL RESEARCH
  • 2013-09. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers in NATURE GENETICS
  • 2013-02. APOBEC3B is an enzymatic source of mutation in breast cancer in NATURE
  • 2012-05. FLASH assembly of TALENs for high-throughput genome editing in NATURE BIOTECHNOLOGY
  • 2014-03. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9 in NATURE
  • 2013-03. Efficient genome editing in zebrafish using a CRISPR-Cas system in NATURE BIOTECHNOLOGY
  • 2014-03. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs in NATURE BIOTECHNOLOGY
  • 2010-09. Genome editing with engineered zinc finger nucleases in NATURE REVIEWS GENETICS
  • 2011-01. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures in NATURE METHODS
  • 2007-07. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases in NATURE BIOTECHNOLOGY
  • 2013-10. CRISPR RNA–guided activation of endogenous human genes in NATURE METHODS
  • 2007-07. An improved zinc-finger nuclease architecture for highly specific genome editing in NATURE BIOTECHNOLOGY
  • 2013-09. DNA targeting specificity of RNA-guided Cas9 nucleases in NATURE BIOTECHNOLOGY
  • 2013-10. RNA-guided gene activation by CRISPR-Cas9–based transcription factors in NATURE METHODS
  • 2013-11. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing in NATURE METHODS
  • Journal

    TITLE

    Nature Biotechnology

    ISSUE

    6

    VOLUME

    32

    Related Patents

  • Full Interrogation Of Nuclease Dsbs And Sequencing (Find-Seq)
  • Hybrid Nucleic Acid Sequences For Genome Engineering
  • Compositions And Methods For Detecting Nucleic Acid Regions
  • Methods For Increasing Cas9-Mediated Engineering Efficiency
  • Novel Crispr Enzymes And Systems
  • Methods And Compositions For Multiplex Rna Guided Genome Editing And Other Rna Technologies
  • Use Of Cationic Lipids To Deliver Cas9
  • De Novo Synthesized Gene Libraries
  • Compositions And Methods For Synthetic Gene Assembly
  • A Crispr-Cas System For A Filamentous Fungal Host Cell
  • Methods For Correcting Presenilin Point Mutations
  • Engineered Crispr-Cas9 Nucleases
  • Using Rna-Guided Foki Nucleases (Rfns) To Increase Specificity For Rna-Guided Genome Editing
  • Evolved Cas9 Proteins For Gene Editing
  • Cas9 Proteins Including Ligand-Dependent Inteins
  • Engineered Crispr-Cas9 Nucleases With Altered Pam Specificity
  • Method For Editing A Genetic Sequence
  • Mrna-Sensing Switchable Grnas
  • Cpf1 Complexes With Reduced Indel Activity
  • Evaluation And Improvement Of Nuclease Cleavage Specificity
  • Cas9-Foki Fusion Proteins And Uses Thereof
  • Compositions And Methods For Targeting Cancer-Specific Sequence Variations
  • Compositions And Methods For Evaluating And Modulating Immune Responses By Detecting And Targeting Gata3
  • Compositions And Methods For Evaluating And Modulating Immune Responses By Use Of Immune Cell Gene Signatures
  • Crispr Mediated Recording Of Cellular Events
  • Functional Genomics Using Crispr-Cas Systems For Saturating Mutagenesis Of Non-Coding Elements, Compositions, Methods, Libraries And Applications Thereof
  • Methods For Nucleic Acid Editing
  • Dead Guides For Crispr Transcription Factors
  • Protected Guide Rnas (Pgrnas)
  • Methods For Identifying And Modulating Co-Occurant Cellular Phenotypes
  • Modulation Of Novel Immune Checkpoint Targets
  • Cas9-Recombinase Fusion Proteins And Uses Thereof
  • Systems, Methods And Compositions For Sequence Manipulation With Optimized Functional Crispr-Cas Systems
  • Crispr Oligonucleotides And Gene Editing
  • Assays For Massively Combinatorial Perturbation Profiling And Cellular Circuit Reconstruction
  • De Novo Synthesized Gene Libraries
  • Use And Production Of Chd8+/- Transgenic Animals With Behavioral Phenotypes Characteristic Of Autism Spectrum Disorder
  • Functional Genomics Using Crispr-Cas Systems, Compositions, Methods, Screens And Applications Thereof
  • Rna-Guided Gene Editing System And Uses Thereof
  • Using Truncated Guide Rnas (Tru-Grnas) To Increase Specificity For Rna-Guided Genome Editing
  • Methods And Compositions For Nuclease Design
  • Engineered Crispr-Cas9 Nucleases With Altered Pam Specificity
  • Cis-Blocked Guide Rna
  • De Novo Synthesized Gene Libraries
  • De Novo Synthesized Gene Libraries
  • Comprehensive In Vitro Reporting Of Cleavage Events By Sequencing (Circle-Seq)
  • Crispr Mediated In Vivo Modeling And Genetic Screening Of Tumor Growth And Metastasis
  • Unbiased Identification Of Double-Strand Breaks And Genomic Rearrangement By Genome-Wide Insert Capture Sequencing
  • Delivery, Use And Therapeutic Applications Of The Crispr-Cas Systems And Compositions For Hbv And Viral Diseases And Disorders
  • A Crispr-Cas System For A Yeast Host Cell
  • Methods For Identifying And Modulating Immune Phenotypes
  • Novel Crispr Enzymes And Systems
  • Method Of Identifying And Treating A Person Having A Predisposition To Or Afflicted With A Cardiometabolic Disease
  • Switchable Grnas Comprising Aptamers
  • Rna-Targeting System
  • Type Vi Crispr Orthologs And Systems
  • Methods For Increasing Cas9-Mediated Engineering Efficiency
  • Engineered Crispr-Cas9 Nucleases With Altered Pam Specificity
  • Delivery, Use And Therapeutic Applications Of The Crispr-Cas Systems And Compositions For Modeling Mutations In Leukocytes
  • Crispr Oligonucleotides And Gene Editing
  • Using Rna-Guided Foki Nucleases (Rfns) To Increase Specificity For Rna-Guided Genome Editing
  • Product And Methods Useful For Modulating And Evaluating Immune Responses
  • Extended Dna-Sensing Grnas
  • Crispr-Related Methods And Compositions With Governing Grnas
  • Gene Editing Reagents With Reduced Toxicity
  • Methods For Identifying And Treating Hemoglobinopathies
  • Delivery, Use And Therapeutic Applications Of Crispr Systems And Compositions For Genome Editing As To Hematopoietic Stem Cells (Hscs)
  • Escorted And Functionalized Guides For Crispr-Cas Systems
  • Permanent Gene Correction By Means Of Nucleotide-Modified Messenger Rna
  • A Crispr-Cas System For A Lipolytic Yeast Host Cell
  • Increasing Specificity For Rna-Guided Genome Editing
  • Compositions And Methods For Evaluating And Modulating Immune Responses
  • Stabilized Reagents For Genome Modification
  • Crispr Having Or Associated With Destabilization Domains
  • Methods For Increasing Cas9-Mediated Engineering Efficiency
  • Methods For Sorting Nucleic Acids And Multiplexed Preparative In Vitro Cloning
  • Devices And Methods For Oligonucleic Acid Library Synthesis
  • Delivery Of Negatively Charged Proteins Using Cationic Lipids
  • Crispr/Cas-Related Methods And Compositions For Treating Leber's Congenital Amaurosis 10 (Lca10)
  • Modulation Of Novel Immune Checkpoint Targets
  • Compositions, Methods And Use Of Synthetic Lethal Screening
  • Compositions And Methods For Evaluating And Modulating Immune Responses By Detecting And Targeting Pou2af1
  • Novel Crispr Enzymes And Systems
  • Functionalized Surfaces And Preparation Thereof
  • Engineered Crispr-Cas9 Nucleases
  • De Novo Synthesized Nucleic Acid Libraries
  • Methods For Identifying A Target Site Of A Cas9 Nuclease
  • Novel Crispr Enzymes And Systems
  • Delivery System For Functional Nucleases
  • Nucleobase Editors And Uses Thereof
  • Type Vi-B Crispr Enzymes And Systems
  • De Novo Synthesized Gene Libraries
  • Cas Variants For Gene Editing
  • Genomewide Unbiased Identification Of Dsbs Evaluated By Sequencing (Guide-Seq)
  • De Novo Synthesized Gene Libraries
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.2908

    DOI

    http://dx.doi.org/10.1038/nbt.2908

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012868720

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24770325


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bacterial Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "CRISPR-Cas Systems", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Deoxyribonucleases, Type II Site-Specific", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Endonucleases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Editing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Multimerization", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Guide", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Fusion Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tsai", 
            "givenName": "Shengdar Q", 
            "id": "sg:person.0742101567.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742101567.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Massachusetts General Hospital", 
              "id": "https://www.grid.ac/institutes/grid.32224.35", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wyvekens", 
            "givenName": "Nicolas", 
            "id": "sg:person.01315554401.67", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315554401.67"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Massachusetts General Hospital", 
              "id": "https://www.grid.ac/institutes/grid.32224.35", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Khayter", 
            "givenName": "Cyd", 
            "id": "sg:person.0650177731.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650177731.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Massachusetts General Hospital", 
              "id": "https://www.grid.ac/institutes/grid.32224.35", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Foden", 
            "givenName": "Jennifer A", 
            "id": "sg:person.01140133375.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01140133375.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Massachusetts General Hospital", 
              "id": "https://www.grid.ac/institutes/grid.32224.35", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Thapar", 
            "givenName": "Vishal", 
            "id": "sg:person.01177723314.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177723314.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Reyon", 
            "givenName": "Deepak", 
            "id": "sg:person.0760565231.98", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760565231.98"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Massachusetts General Hospital", 
              "id": "https://www.grid.ac/institutes/grid.32224.35", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Goodwin", 
            "givenName": "Mathew J", 
            "id": "sg:person.0720077755.84", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0720077755.84"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Aryee", 
            "givenName": "Martin J", 
            "id": "sg:person.0636535214.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0636535214.09"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.", 
                "Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Joung", 
            "givenName": "J Keith", 
            "id": "sg:person.0667170477.75", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0667170477.75"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nbt1319", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002154526", 
              "https://doi.org/10.1038/nbt1319"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2013.08.021", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002481722"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2014.02.001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004290844"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2673", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007302590", 
              "https://doi.org/10.1038/nbt.2673"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2623", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009511624", 
              "https://doi.org/10.1038/nbt.2623"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.1539", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010147854", 
              "https://doi.org/10.1038/nmeth.1539"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.1539", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010147854", 
              "https://doi.org/10.1038/nmeth.1539"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gr.162339.113", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010306401"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1247997", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010970903"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2647", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012543463", 
              "https://doi.org/10.1038/nbt.2647"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1261/rna.030882.111", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015360819"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg2842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018939216", 
              "https://doi.org/10.1038/nrg2842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg2842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018939216", 
              "https://doi.org/10.1038/nrg2842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2702", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020175364", 
              "https://doi.org/10.1038/ng.2702"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/jipb.12152", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021858851"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1232033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022072971"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.2600", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024354143", 
              "https://doi.org/10.1038/nmeth.2600"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkq319", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024844693"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkq319", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024844693"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2501", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024988605", 
              "https://doi.org/10.1038/nbt.2501"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.2681", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028304735", 
              "https://doi.org/10.1038/nmeth.2681"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1192272", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030675682"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11881", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032796931", 
              "https://doi.org/10.1038/nature11881"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature13011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037342101", 
              "https://doi.org/10.1038/nature13011"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/bioinformatics/btp324", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038266369"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038520013", 
              "https://doi.org/10.1038/nbt.2842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2170", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040026920", 
              "https://doi.org/10.1038/nbt.2170"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2675", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041659759", 
              "https://doi.org/10.1038/nbt.2675"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1225829", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041850060"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt1317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045480104", 
              "https://doi.org/10.1038/nbt1317"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2013.122", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048353952", 
              "https://doi.org/10.1038/cr.2013.122"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2808", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048637524", 
              "https://doi.org/10.1038/nbt.2808"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.2598", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049500416", 
              "https://doi.org/10.1038/nmeth.2598"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm3486", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050461034", 
              "https://doi.org/10.1038/nrm3486"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2014-06", 
        "datePublishedReg": "2014-06-01", 
        "description": "Monomeric CRISPR-Cas9 nucleases are widely used for targeted genome editing but can induce unwanted off-target mutations with high frequencies. Here we describe dimeric RNA-guided FokI nucleases (RFNs) that can recognize extended sequences and edit endogenous genes with high efficiencies in human cells. RFN cleavage activity depends strictly on the binding of two guide RNAs (gRNAs) to DNA with a defined spacing and orientation substantially reducing the likelihood that a suitable target site will occur more than once in the genome and therefore improving specificities relative to wild-type Cas9 monomers. RFNs guided by a single gRNA generally induce lower levels of unwanted mutations than matched monomeric Cas9 nickases. In addition, we describe a simple method for expressing multiple gRNAs bearing any 5' end nucleotide, which gives dimeric RFNs a broad targeting range. RFNs combine the ease of RNA-based targeting with the specificity enhancement inherent to dimerization and are likely to be useful in applications that require highly precise genome editing. ", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/nbt.2908", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2465415", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2354980", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2520480", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2383486", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2440618", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1115214", 
            "issn": [
              "1087-0156", 
              "1546-1696"
            ], 
            "name": "Nature Biotechnology", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "32"
          }
        ], 
        "name": "Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing", 
        "pagination": "569", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "3d4e326c7b90925585c8f6cfb41e27bb35392d7dec06609452dfdd2b825fd1c3"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "24770325"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "9604648"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/nbt.2908"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1012868720"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/nbt.2908", 
          "https://app.dimensions.ai/details/publication/pub.1012868720"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T18:09", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8675_00000435.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/nbt.2908"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nbt.2908'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nbt.2908'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nbt.2908'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nbt.2908'


     

    This table displays all metadata directly associated to this object as RDF triples.

    292 TRIPLES      21 PREDICATES      69 URIs      30 LITERALS      18 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/nbt.2908 schema:about N14867b14af284559ba8037650ef869d3
    2 N26aa99bf9c07428d8e34d49fc600b73a
    3 N35fdf1dbff544a6fb44f2e3806c40cfb
    4 N49ee7b7d291e466197f653b1816d07c5
    5 N60cbed01178745978fb5b6ee22b88eea
    6 N724efc79e0bd41858b2d083444e5e5c6
    7 N8b0d3e68da494347bb4eb2e68b0a0687
    8 Ndfe44dce96914fbbafc93d55277bd730
    9 Ne9873f3ce36146c78ba1a3e4ff4e1c46
    10 anzsrc-for:06
    11 anzsrc-for:0604
    12 schema:author N8b7f02ba0eb1498fb85a3e7b2e5504ae
    13 schema:citation sg:pub.10.1038/cr.2013.122
    14 sg:pub.10.1038/nature11881
    15 sg:pub.10.1038/nature13011
    16 sg:pub.10.1038/nbt.2170
    17 sg:pub.10.1038/nbt.2501
    18 sg:pub.10.1038/nbt.2623
    19 sg:pub.10.1038/nbt.2647
    20 sg:pub.10.1038/nbt.2673
    21 sg:pub.10.1038/nbt.2675
    22 sg:pub.10.1038/nbt.2808
    23 sg:pub.10.1038/nbt.2842
    24 sg:pub.10.1038/nbt1317
    25 sg:pub.10.1038/nbt1319
    26 sg:pub.10.1038/ng.2702
    27 sg:pub.10.1038/nmeth.1539
    28 sg:pub.10.1038/nmeth.2598
    29 sg:pub.10.1038/nmeth.2600
    30 sg:pub.10.1038/nmeth.2681
    31 sg:pub.10.1038/nrg2842
    32 sg:pub.10.1038/nrm3486
    33 https://doi.org/10.1016/j.cell.2013.08.021
    34 https://doi.org/10.1016/j.cell.2014.02.001
    35 https://doi.org/10.1093/bioinformatics/btp324
    36 https://doi.org/10.1093/nar/gkq319
    37 https://doi.org/10.1101/gr.162339.113
    38 https://doi.org/10.1111/jipb.12152
    39 https://doi.org/10.1126/science.1192272
    40 https://doi.org/10.1126/science.1225829
    41 https://doi.org/10.1126/science.1232033
    42 https://doi.org/10.1126/science.1247997
    43 https://doi.org/10.1261/rna.030882.111
    44 schema:datePublished 2014-06
    45 schema:datePublishedReg 2014-06-01
    46 schema:description Monomeric CRISPR-Cas9 nucleases are widely used for targeted genome editing but can induce unwanted off-target mutations with high frequencies. Here we describe dimeric RNA-guided FokI nucleases (RFNs) that can recognize extended sequences and edit endogenous genes with high efficiencies in human cells. RFN cleavage activity depends strictly on the binding of two guide RNAs (gRNAs) to DNA with a defined spacing and orientation substantially reducing the likelihood that a suitable target site will occur more than once in the genome and therefore improving specificities relative to wild-type Cas9 monomers. RFNs guided by a single gRNA generally induce lower levels of unwanted mutations than matched monomeric Cas9 nickases. In addition, we describe a simple method for expressing multiple gRNAs bearing any 5' end nucleotide, which gives dimeric RFNs a broad targeting range. RFNs combine the ease of RNA-based targeting with the specificity enhancement inherent to dimerization and are likely to be useful in applications that require highly precise genome editing.
    47 schema:genre research_article
    48 schema:inLanguage en
    49 schema:isAccessibleForFree true
    50 schema:isPartOf N66f1ca5856e6444ba4c922e4d113a3a3
    51 N70ebf89881bd42468e9457ea3603a688
    52 sg:journal.1115214
    53 schema:name Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing
    54 schema:pagination 569
    55 schema:productId N31e0655460d94c5eac888421f0ae757a
    56 N6c24061f23ea445abe2b7854f9ee0cd3
    57 N76bbd82c9f294bf5ade2e45d3e27ebb7
    58 N8831a25fa1974c0990aedeab37d59a51
    59 N9ff272ad0d45488cb22cf2c8c989985f
    60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012868720
    61 https://doi.org/10.1038/nbt.2908
    62 schema:sdDatePublished 2019-04-10T18:09
    63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    64 schema:sdPublisher Ne352e20932464a998d7df934f32eb67e
    65 schema:url https://www.nature.com/articles/nbt.2908
    66 sgo:license sg:explorer/license/
    67 sgo:sdDataset articles
    68 rdf:type schema:ScholarlyArticle
    69 N0189a72036464ed68b986e20bc518dd3 rdf:first sg:person.01315554401.67
    70 rdf:rest N6912c317978a420384b9f6c1f539d019
    71 N14867b14af284559ba8037650ef869d3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    72 schema:name Protein Multimerization
    73 rdf:type schema:DefinedTerm
    74 N26aa99bf9c07428d8e34d49fc600b73a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    75 schema:name CRISPR-Cas Systems
    76 rdf:type schema:DefinedTerm
    77 N2821242acb8442699681cc8de51086b7 rdf:first sg:person.01140133375.19
    78 rdf:rest Ncd3aa3f6ec4b4df0b81c146b72fa6702
    79 N295f1288371f48028010f1ce45d4a1d1 rdf:first sg:person.0760565231.98
    80 rdf:rest N80ed95d073d24267856503e73446a696
    81 N31e0655460d94c5eac888421f0ae757a schema:name dimensions_id
    82 schema:value pub.1012868720
    83 rdf:type schema:PropertyValue
    84 N35fdf1dbff544a6fb44f2e3806c40cfb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    85 schema:name Bacterial Proteins
    86 rdf:type schema:DefinedTerm
    87 N49ee7b7d291e466197f653b1816d07c5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    88 schema:name Endonucleases
    89 rdf:type schema:DefinedTerm
    90 N55c20d51563d4fb49fe760b2b6f8fc6d rdf:first sg:person.0667170477.75
    91 rdf:rest rdf:nil
    92 N60cbed01178745978fb5b6ee22b88eea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    93 schema:name Recombinant Fusion Proteins
    94 rdf:type schema:DefinedTerm
    95 N66f1ca5856e6444ba4c922e4d113a3a3 schema:volumeNumber 32
    96 rdf:type schema:PublicationVolume
    97 N6912c317978a420384b9f6c1f539d019 rdf:first sg:person.0650177731.59
    98 rdf:rest N2821242acb8442699681cc8de51086b7
    99 N6c24061f23ea445abe2b7854f9ee0cd3 schema:name readcube_id
    100 schema:value 3d4e326c7b90925585c8f6cfb41e27bb35392d7dec06609452dfdd2b825fd1c3
    101 rdf:type schema:PropertyValue
    102 N70ebf89881bd42468e9457ea3603a688 schema:issueNumber 6
    103 rdf:type schema:PublicationIssue
    104 N724efc79e0bd41858b2d083444e5e5c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    105 schema:name Humans
    106 rdf:type schema:DefinedTerm
    107 N76bbd82c9f294bf5ade2e45d3e27ebb7 schema:name doi
    108 schema:value 10.1038/nbt.2908
    109 rdf:type schema:PropertyValue
    110 N80ed95d073d24267856503e73446a696 rdf:first sg:person.0720077755.84
    111 rdf:rest Nfcc942d78ad44f1cbc72053080ad4619
    112 N8831a25fa1974c0990aedeab37d59a51 schema:name pubmed_id
    113 schema:value 24770325
    114 rdf:type schema:PropertyValue
    115 N8b0d3e68da494347bb4eb2e68b0a0687 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    116 schema:name RNA, Guide
    117 rdf:type schema:DefinedTerm
    118 N8b7f02ba0eb1498fb85a3e7b2e5504ae rdf:first sg:person.0742101567.17
    119 rdf:rest N0189a72036464ed68b986e20bc518dd3
    120 N9ff272ad0d45488cb22cf2c8c989985f schema:name nlm_unique_id
    121 schema:value 9604648
    122 rdf:type schema:PropertyValue
    123 Ncd3aa3f6ec4b4df0b81c146b72fa6702 rdf:first sg:person.01177723314.50
    124 rdf:rest N295f1288371f48028010f1ce45d4a1d1
    125 Ndfe44dce96914fbbafc93d55277bd730 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Deoxyribonucleases, Type II Site-Specific
    127 rdf:type schema:DefinedTerm
    128 Ne352e20932464a998d7df934f32eb67e schema:name Springer Nature - SN SciGraph project
    129 rdf:type schema:Organization
    130 Ne9873f3ce36146c78ba1a3e4ff4e1c46 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Gene Editing
    132 rdf:type schema:DefinedTerm
    133 Nfcc942d78ad44f1cbc72053080ad4619 rdf:first sg:person.0636535214.09
    134 rdf:rest N55c20d51563d4fb49fe760b2b6f8fc6d
    135 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    136 schema:name Biological Sciences
    137 rdf:type schema:DefinedTerm
    138 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    139 schema:name Genetics
    140 rdf:type schema:DefinedTerm
    141 sg:grant.2354980 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2908
    142 rdf:type schema:MonetaryGrant
    143 sg:grant.2383486 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2908
    144 rdf:type schema:MonetaryGrant
    145 sg:grant.2440618 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2908
    146 rdf:type schema:MonetaryGrant
    147 sg:grant.2465415 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2908
    148 rdf:type schema:MonetaryGrant
    149 sg:grant.2520480 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2908
    150 rdf:type schema:MonetaryGrant
    151 sg:journal.1115214 schema:issn 1087-0156
    152 1546-1696
    153 schema:name Nature Biotechnology
    154 rdf:type schema:Periodical
    155 sg:person.01140133375.19 schema:affiliation https://www.grid.ac/institutes/grid.32224.35
    156 schema:familyName Foden
    157 schema:givenName Jennifer A
    158 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01140133375.19
    159 rdf:type schema:Person
    160 sg:person.01177723314.50 schema:affiliation https://www.grid.ac/institutes/grid.32224.35
    161 schema:familyName Thapar
    162 schema:givenName Vishal
    163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177723314.50
    164 rdf:type schema:Person
    165 sg:person.01315554401.67 schema:affiliation https://www.grid.ac/institutes/grid.32224.35
    166 schema:familyName Wyvekens
    167 schema:givenName Nicolas
    168 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315554401.67
    169 rdf:type schema:Person
    170 sg:person.0636535214.09 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    171 schema:familyName Aryee
    172 schema:givenName Martin J
    173 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0636535214.09
    174 rdf:type schema:Person
    175 sg:person.0650177731.59 schema:affiliation https://www.grid.ac/institutes/grid.32224.35
    176 schema:familyName Khayter
    177 schema:givenName Cyd
    178 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650177731.59
    179 rdf:type schema:Person
    180 sg:person.0667170477.75 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    181 schema:familyName Joung
    182 schema:givenName J Keith
    183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0667170477.75
    184 rdf:type schema:Person
    185 sg:person.0720077755.84 schema:affiliation https://www.grid.ac/institutes/grid.32224.35
    186 schema:familyName Goodwin
    187 schema:givenName Mathew J
    188 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0720077755.84
    189 rdf:type schema:Person
    190 sg:person.0742101567.17 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    191 schema:familyName Tsai
    192 schema:givenName Shengdar Q
    193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742101567.17
    194 rdf:type schema:Person
    195 sg:person.0760565231.98 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    196 schema:familyName Reyon
    197 schema:givenName Deepak
    198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760565231.98
    199 rdf:type schema:Person
    200 sg:pub.10.1038/cr.2013.122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048353952
    201 https://doi.org/10.1038/cr.2013.122
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1038/nature11881 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032796931
    204 https://doi.org/10.1038/nature11881
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1038/nature13011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037342101
    207 https://doi.org/10.1038/nature13011
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1038/nbt.2170 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040026920
    210 https://doi.org/10.1038/nbt.2170
    211 rdf:type schema:CreativeWork
    212 sg:pub.10.1038/nbt.2501 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024988605
    213 https://doi.org/10.1038/nbt.2501
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1038/nbt.2623 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009511624
    216 https://doi.org/10.1038/nbt.2623
    217 rdf:type schema:CreativeWork
    218 sg:pub.10.1038/nbt.2647 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012543463
    219 https://doi.org/10.1038/nbt.2647
    220 rdf:type schema:CreativeWork
    221 sg:pub.10.1038/nbt.2673 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007302590
    222 https://doi.org/10.1038/nbt.2673
    223 rdf:type schema:CreativeWork
    224 sg:pub.10.1038/nbt.2675 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041659759
    225 https://doi.org/10.1038/nbt.2675
    226 rdf:type schema:CreativeWork
    227 sg:pub.10.1038/nbt.2808 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048637524
    228 https://doi.org/10.1038/nbt.2808
    229 rdf:type schema:CreativeWork
    230 sg:pub.10.1038/nbt.2842 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038520013
    231 https://doi.org/10.1038/nbt.2842
    232 rdf:type schema:CreativeWork
    233 sg:pub.10.1038/nbt1317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045480104
    234 https://doi.org/10.1038/nbt1317
    235 rdf:type schema:CreativeWork
    236 sg:pub.10.1038/nbt1319 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002154526
    237 https://doi.org/10.1038/nbt1319
    238 rdf:type schema:CreativeWork
    239 sg:pub.10.1038/ng.2702 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020175364
    240 https://doi.org/10.1038/ng.2702
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1038/nmeth.1539 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010147854
    243 https://doi.org/10.1038/nmeth.1539
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1038/nmeth.2598 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049500416
    246 https://doi.org/10.1038/nmeth.2598
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1038/nmeth.2600 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024354143
    249 https://doi.org/10.1038/nmeth.2600
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1038/nmeth.2681 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028304735
    252 https://doi.org/10.1038/nmeth.2681
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1038/nrg2842 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018939216
    255 https://doi.org/10.1038/nrg2842
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1038/nrm3486 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050461034
    258 https://doi.org/10.1038/nrm3486
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1016/j.cell.2013.08.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002481722
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1016/j.cell.2014.02.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004290844
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1093/bioinformatics/btp324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038266369
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1093/nar/gkq319 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024844693
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1101/gr.162339.113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010306401
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1111/jipb.12152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021858851
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1126/science.1192272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030675682
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1126/science.1225829 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041850060
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1126/science.1232033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022072971
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1126/science.1247997 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010970903
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1261/rna.030882.111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015360819
    281 rdf:type schema:CreativeWork
    282 https://www.grid.ac/institutes/grid.32224.35 schema:alternateName Massachusetts General Hospital
    283 schema:name Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    284 Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    285 Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    286 rdf:type schema:Organization
    287 https://www.grid.ac/institutes/grid.38142.3c schema:alternateName Harvard University
    288 schema:name Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    289 Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    290 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
    291 Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
    292 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...