Massively parallel functional dissection of mammalian enhancers in vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-03

AUTHORS

Rupali P Patwardhan, Joseph B Hiatt, Daniela M Witten, Mee J Kim, Robin P Smith, Dalit May, Choli Lee, Jennifer M Andrie, Su-In Lee, Gregory M Cooper, Nadav Ahituv, Len A Pennacchio, Jay Shendure

ABSTRACT

The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a unique sequence tag embedded within a transcriptional cassette. We introduced each enhancer library into mouse liver and measured the relative activities of individual haplotypes en masse by sequencing the transcribed tags. Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. The functional consequence of most mutations was modest, with ∼22% affecting activity by >1.2-fold and ∼3% by >2-fold. Several, but not all, positions with higher effects showed evidence for purifying selection, or co-localized with known liver-associated transcription factor binding sites, demonstrating the value of empirical high-resolution functional analysis. More... »

PAGES

265

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.2136

DOI

http://dx.doi.org/10.1038/nbt.2136

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044559969

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22371081


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": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Binding Sites", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Enhancer Elements, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Evolution, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genes, Reporter", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Haplotypes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Linear Models", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Liver", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutagenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcription, Genetic", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Patwardhan", 
        "givenName": "Rupali P", 
        "id": "sg:person.01154431563.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01154431563.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hiatt", 
        "givenName": "Joseph B", 
        "id": "sg:person.01355355742.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355355742.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Biostatistics, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Witten", 
        "givenName": "Daniela M", 
        "id": "sg:person.010574162307.32", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010574162307.32"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California, San Francisco", 
          "id": "https://www.grid.ac/institutes/grid.266102.1", 
          "name": [
            "Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Mee J", 
        "id": "sg:person.013474666314.94", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013474666314.94"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California, San Francisco", 
          "id": "https://www.grid.ac/institutes/grid.266102.1", 
          "name": [
            "Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Smith", 
        "givenName": "Robin P", 
        "id": "sg:person.01313616715.23", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313616715.23"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Lawrence Berkeley National Laboratory", 
          "id": "https://www.grid.ac/institutes/grid.184769.5", 
          "name": [
            "Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "May", 
        "givenName": "Dalit", 
        "id": "sg:person.01077111116.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01077111116.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lee", 
        "givenName": "Choli", 
        "id": "sg:person.014504652317.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014504652317.99"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Andrie", 
        "givenName": "Jennifer M", 
        "id": "sg:person.0775731063.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775731063.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA.", 
            "Department of Computer Science, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lee", 
        "givenName": "Su-In", 
        "id": "sg:person.013662722625.83", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013662722625.83"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "HudsonAlpha Institute for Biotechnology", 
          "id": "https://www.grid.ac/institutes/grid.417691.c", 
          "name": [
            "HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cooper", 
        "givenName": "Gregory M", 
        "id": "sg:person.01314025630.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01314025630.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California, San Francisco", 
          "id": "https://www.grid.ac/institutes/grid.266102.1", 
          "name": [
            "Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ahituv", 
        "givenName": "Nadav", 
        "id": "sg:person.0637155372.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0637155372.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Joint Genome Institute", 
          "id": "https://www.grid.ac/institutes/grid.451309.a", 
          "name": [
            "Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California, USA.", 
            "Department of Energy Joint Genome Institute, Walnut Creek, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pennacchio", 
        "givenName": "Len A", 
        "id": "sg:person.01022360446.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01022360446.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Washington", 
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": [
            "Department of Genome Sciences, University of Washington, Seattle, Washington, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shendure", 
        "givenName": "Jay", 
        "id": "sg:person.01221110417.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221110417.53"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1101/gr.6034307", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005155799"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0006-291x(05)80244-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006684584"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.650", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009136820", 
          "https://doi.org/10.1038/ng.650"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.650", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009136820", 
          "https://doi.org/10.1038/ng.650"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt.1589", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010374914", 
          "https://doi.org/10.1038/nbt.1589"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt.1589", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010374914", 
          "https://doi.org/10.1038/nbt.1589"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature09534", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010608717", 
          "https://doi.org/10.1038/nature09534"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature09534", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010608717", 
          "https://doi.org/10.1038/nature09534"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gr.3577405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014343625"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.271.7.3469", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015325852"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.37.22058", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015326720"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0903103106", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020299353"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature07730", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021031479", 
          "https://doi.org/10.1038/nature07730"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth.1416", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025089276", 
          "https://doi.org/10.1038/nmeth.1416"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth.1416", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025089276", 
          "https://doi.org/10.1038/nmeth.1416"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkg585", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025416063"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1186176", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030603437"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pbio.1001046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031377769"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-genom-082509-141651", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034711186"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m204047200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035703522"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature09906", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043304663", 
          "https://doi.org/10.1038/nature09906"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/dvdy.22535", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044249979"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg3046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044439384", 
          "https://doi.org/10.1038/nrg3046"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.38.22577", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045309248"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.288.5463.136", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045941060"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2010.353", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047311871", 
          "https://doi.org/10.1038/clpt.2010.353"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/426833", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049755198"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.2007.55", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053463486", 
          "https://doi.org/10.1038/ng.2007.55"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/10430349950017734", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059202919"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.2994214", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062580043"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2012-03", 
    "datePublishedReg": "2012-03-01", 
    "description": "The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a unique sequence tag embedded within a transcriptional cassette. We introduced each enhancer library into mouse liver and measured the relative activities of individual haplotypes en masse by sequencing the transcribed tags. Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. The functional consequence of most mutations was modest, with \u223c22% affecting activity by >1.2-fold and \u223c3% by >2-fold. Several, but not all, positions with higher effects showed evidence for purifying selection, or co-localized with known liver-associated transcription factor binding sites, demonstrating the value of empirical high-resolution functional analysis.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nbt.2136", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2355505", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2529271", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2438977", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2683689", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2690866", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2357962", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2527964", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2696056", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1115214", 
        "issn": [
          "1087-0156", 
          "1546-1696"
        ], 
        "name": "Nature Biotechnology", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "3", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "30"
      }
    ], 
    "name": "Massively parallel functional dissection of mammalian enhancers in vivo", 
    "pagination": "265", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "d440ffed6e9240cb074fc197a1ac3ae36fcc781767a4da9c02cbe003a1b834cb"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "22371081"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "9604648"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nbt.2136"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1044559969"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nbt.2136", 
      "https://app.dimensions.ai/details/publication/pub.1044559969"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T01:48", 
    "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_8700_00000436.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nbt.2136"
  }
]
 

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.2136'

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.2136'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nbt.2136'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nbt.2136'


 

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

327 TRIPLES      21 PREDICATES      69 URIs      35 LITERALS      23 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nbt.2136 schema:about N21ce70f5c8604bd5ac3b4970a14a2f3a
2 N2cc6d50e8e894f00938f1b552ce68964
3 N35d56448f3224ffa994c39862076dff0
4 N4aed1adf79da403598b0d378c89bbad6
5 N637f3f68930b4f559f5fb3e42e2d92af
6 N7fb5d2f392ee4cb8b42954a73972441a
7 N91db5e3ba31b4ea1a5c68ccf7527fb29
8 N92dc028231254be6a75846036533f348
9 N96715a8637814ed8bb8e2e5fb9e78f17
10 Na355f0a3d9534c42987378013947ce7f
11 Nb11c52f13e5c4184971e82a163f98064
12 Nd54fc70e6315427b8ca5c8489684db3e
13 Nef93f56939da4c0dbfed95104afb4c04
14 Nf10ede431182442aa915c063f07b279a
15 anzsrc-for:06
16 anzsrc-for:0604
17 schema:author N4899408097d04531af83f4c0daf28416
18 schema:citation sg:pub.10.1038/clpt.2010.353
19 sg:pub.10.1038/nature07730
20 sg:pub.10.1038/nature09534
21 sg:pub.10.1038/nature09906
22 sg:pub.10.1038/nbt.1589
23 sg:pub.10.1038/ng.2007.55
24 sg:pub.10.1038/ng.650
25 sg:pub.10.1038/nmeth.1416
26 sg:pub.10.1038/nrg3046
27 https://doi.org/10.1002/dvdy.22535
28 https://doi.org/10.1016/s0006-291x(05)80244-x
29 https://doi.org/10.1073/pnas.0903103106
30 https://doi.org/10.1074/jbc.270.37.22058
31 https://doi.org/10.1074/jbc.270.38.22577
32 https://doi.org/10.1074/jbc.271.7.3469
33 https://doi.org/10.1074/jbc.m204047200
34 https://doi.org/10.1086/426833
35 https://doi.org/10.1089/10430349950017734
36 https://doi.org/10.1093/nar/gkg585
37 https://doi.org/10.1101/gr.3577405
38 https://doi.org/10.1101/gr.6034307
39 https://doi.org/10.1126/science.1186176
40 https://doi.org/10.1126/science.288.5463.136
41 https://doi.org/10.1126/science.2994214
42 https://doi.org/10.1146/annurev-genom-082509-141651
43 https://doi.org/10.1371/journal.pbio.1001046
44 schema:datePublished 2012-03
45 schema:datePublishedReg 2012-03-01
46 schema:description The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a unique sequence tag embedded within a transcriptional cassette. We introduced each enhancer library into mouse liver and measured the relative activities of individual haplotypes en masse by sequencing the transcribed tags. Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. The functional consequence of most mutations was modest, with ∼22% affecting activity by >1.2-fold and ∼3% by >2-fold. Several, but not all, positions with higher effects showed evidence for purifying selection, or co-localized with known liver-associated transcription factor binding sites, demonstrating the value of empirical high-resolution functional analysis.
47 schema:genre research_article
48 schema:inLanguage en
49 schema:isAccessibleForFree true
50 schema:isPartOf N0d636365c3b74801a2d51d8276051f7b
51 N3ef3bc8d92fc44c0b911bf2fd5e5d042
52 sg:journal.1115214
53 schema:name Massively parallel functional dissection of mammalian enhancers in vivo
54 schema:pagination 265
55 schema:productId N34b7cff89c0043648c2fc29bdb695348
56 N6a7daaec95dd4d3086e3a7651bf5d636
57 N9a721dfc07e84ed8833f66c8e5645d5f
58 Nb0965858cf7b4b8e922a17422528e3a1
59 Nca249e74830d46a2803a1c5a2e53478d
60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044559969
61 https://doi.org/10.1038/nbt.2136
62 schema:sdDatePublished 2019-04-11T01:48
63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
64 schema:sdPublisher N895645325e5a436189531f2a60e6ca4e
65 schema:url https://www.nature.com/articles/nbt.2136
66 sgo:license sg:explorer/license/
67 sgo:sdDataset articles
68 rdf:type schema:ScholarlyArticle
69 N01006f288acc421da3c8f63c7d13dc22 rdf:first sg:person.0775731063.54
70 rdf:rest N7d8d9b92d2ba432ca2eb6a0dd522d03a
71 N0d636365c3b74801a2d51d8276051f7b schema:issueNumber 3
72 rdf:type schema:PublicationIssue
73 N175e4779c8484a7095cd4c6d7c0a4a67 rdf:first sg:person.010574162307.32
74 rdf:rest N82751602a9d34573960fc92b157f99ff
75 N21ce70f5c8604bd5ac3b4970a14a2f3a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
76 schema:name Genes, Reporter
77 rdf:type schema:DefinedTerm
78 N2cc6d50e8e894f00938f1b552ce68964 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
79 schema:name Enhancer Elements, Genetic
80 rdf:type schema:DefinedTerm
81 N34b7cff89c0043648c2fc29bdb695348 schema:name readcube_id
82 schema:value d440ffed6e9240cb074fc197a1ac3ae36fcc781767a4da9c02cbe003a1b834cb
83 rdf:type schema:PropertyValue
84 N35d56448f3224ffa994c39862076dff0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
85 schema:name Binding Sites
86 rdf:type schema:DefinedTerm
87 N3ef3bc8d92fc44c0b911bf2fd5e5d042 schema:volumeNumber 30
88 rdf:type schema:PublicationVolume
89 N40f37ff5445e465a8b6f9923256d41e5 rdf:first sg:person.01355355742.29
90 rdf:rest N175e4779c8484a7095cd4c6d7c0a4a67
91 N4899408097d04531af83f4c0daf28416 rdf:first sg:person.01154431563.34
92 rdf:rest N40f37ff5445e465a8b6f9923256d41e5
93 N4aed1adf79da403598b0d378c89bbad6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Animals
95 rdf:type schema:DefinedTerm
96 N5f9aa9d2fed3428eadfdc1d7d43ddbb8 rdf:first sg:person.0637155372.91
97 rdf:rest Ndc21e6bc3b024f36b17b6eebaa14baa6
98 N637f3f68930b4f559f5fb3e42e2d92af schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
99 schema:name Mice
100 rdf:type schema:DefinedTerm
101 N6a7daaec95dd4d3086e3a7651bf5d636 schema:name pubmed_id
102 schema:value 22371081
103 rdf:type schema:PropertyValue
104 N7d8d9b92d2ba432ca2eb6a0dd522d03a rdf:first sg:person.013662722625.83
105 rdf:rest Ne696c54fcc6b48b7a06f8987123ead78
106 N7fb5d2f392ee4cb8b42954a73972441a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Linear Models
108 rdf:type schema:DefinedTerm
109 N82751602a9d34573960fc92b157f99ff rdf:first sg:person.013474666314.94
110 rdf:rest N9e0827c56d784c119ab07f2e06d4d78b
111 N895645325e5a436189531f2a60e6ca4e schema:name Springer Nature - SN SciGraph project
112 rdf:type schema:Organization
113 N8a3e4ef2f21f45c39658c5e0b70ede83 rdf:first sg:person.01077111116.41
114 rdf:rest Nbb722eedb08d4b9fb9713f712c6aaf40
115 N91db5e3ba31b4ea1a5c68ccf7527fb29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
116 schema:name Transcription, Genetic
117 rdf:type schema:DefinedTerm
118 N92dc028231254be6a75846036533f348 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Humans
120 rdf:type schema:DefinedTerm
121 N96715a8637814ed8bb8e2e5fb9e78f17 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
122 schema:name Mutation
123 rdf:type schema:DefinedTerm
124 N9a721dfc07e84ed8833f66c8e5645d5f schema:name doi
125 schema:value 10.1038/nbt.2136
126 rdf:type schema:PropertyValue
127 N9e0827c56d784c119ab07f2e06d4d78b rdf:first sg:person.01313616715.23
128 rdf:rest N8a3e4ef2f21f45c39658c5e0b70ede83
129 Na355f0a3d9534c42987378013947ce7f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Liver
131 rdf:type schema:DefinedTerm
132 Nb0965858cf7b4b8e922a17422528e3a1 schema:name nlm_unique_id
133 schema:value 9604648
134 rdf:type schema:PropertyValue
135 Nb11c52f13e5c4184971e82a163f98064 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
136 schema:name Mutagenesis
137 rdf:type schema:DefinedTerm
138 Nbb722eedb08d4b9fb9713f712c6aaf40 rdf:first sg:person.014504652317.99
139 rdf:rest N01006f288acc421da3c8f63c7d13dc22
140 Nbe9cfd57c4fe458b949962451f82597e rdf:first sg:person.01221110417.53
141 rdf:rest rdf:nil
142 Nca249e74830d46a2803a1c5a2e53478d schema:name dimensions_id
143 schema:value pub.1044559969
144 rdf:type schema:PropertyValue
145 Nd54fc70e6315427b8ca5c8489684db3e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Transcription Factors
147 rdf:type schema:DefinedTerm
148 Ndc21e6bc3b024f36b17b6eebaa14baa6 rdf:first sg:person.01022360446.35
149 rdf:rest Nbe9cfd57c4fe458b949962451f82597e
150 Ne696c54fcc6b48b7a06f8987123ead78 rdf:first sg:person.01314025630.13
151 rdf:rest N5f9aa9d2fed3428eadfdc1d7d43ddbb8
152 Nef93f56939da4c0dbfed95104afb4c04 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Evolution, Molecular
154 rdf:type schema:DefinedTerm
155 Nf10ede431182442aa915c063f07b279a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Haplotypes
157 rdf:type schema:DefinedTerm
158 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
159 schema:name Biological Sciences
160 rdf:type schema:DefinedTerm
161 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
162 schema:name Genetics
163 rdf:type schema:DefinedTerm
164 sg:grant.2355505 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
165 rdf:type schema:MonetaryGrant
166 sg:grant.2357962 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
167 rdf:type schema:MonetaryGrant
168 sg:grant.2438977 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
169 rdf:type schema:MonetaryGrant
170 sg:grant.2527964 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
171 rdf:type schema:MonetaryGrant
172 sg:grant.2529271 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
173 rdf:type schema:MonetaryGrant
174 sg:grant.2683689 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
175 rdf:type schema:MonetaryGrant
176 sg:grant.2690866 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
177 rdf:type schema:MonetaryGrant
178 sg:grant.2696056 http://pending.schema.org/fundedItem sg:pub.10.1038/nbt.2136
179 rdf:type schema:MonetaryGrant
180 sg:journal.1115214 schema:issn 1087-0156
181 1546-1696
182 schema:name Nature Biotechnology
183 rdf:type schema:Periodical
184 sg:person.01022360446.35 schema:affiliation https://www.grid.ac/institutes/grid.451309.a
185 schema:familyName Pennacchio
186 schema:givenName Len A
187 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01022360446.35
188 rdf:type schema:Person
189 sg:person.010574162307.32 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
190 schema:familyName Witten
191 schema:givenName Daniela M
192 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010574162307.32
193 rdf:type schema:Person
194 sg:person.01077111116.41 schema:affiliation https://www.grid.ac/institutes/grid.184769.5
195 schema:familyName May
196 schema:givenName Dalit
197 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01077111116.41
198 rdf:type schema:Person
199 sg:person.01154431563.34 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
200 schema:familyName Patwardhan
201 schema:givenName Rupali P
202 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01154431563.34
203 rdf:type schema:Person
204 sg:person.01221110417.53 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
205 schema:familyName Shendure
206 schema:givenName Jay
207 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221110417.53
208 rdf:type schema:Person
209 sg:person.01313616715.23 schema:affiliation https://www.grid.ac/institutes/grid.266102.1
210 schema:familyName Smith
211 schema:givenName Robin P
212 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313616715.23
213 rdf:type schema:Person
214 sg:person.01314025630.13 schema:affiliation https://www.grid.ac/institutes/grid.417691.c
215 schema:familyName Cooper
216 schema:givenName Gregory M
217 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01314025630.13
218 rdf:type schema:Person
219 sg:person.013474666314.94 schema:affiliation https://www.grid.ac/institutes/grid.266102.1
220 schema:familyName Kim
221 schema:givenName Mee J
222 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013474666314.94
223 rdf:type schema:Person
224 sg:person.01355355742.29 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
225 schema:familyName Hiatt
226 schema:givenName Joseph B
227 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355355742.29
228 rdf:type schema:Person
229 sg:person.013662722625.83 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
230 schema:familyName Lee
231 schema:givenName Su-In
232 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013662722625.83
233 rdf:type schema:Person
234 sg:person.014504652317.99 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
235 schema:familyName Lee
236 schema:givenName Choli
237 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014504652317.99
238 rdf:type schema:Person
239 sg:person.0637155372.91 schema:affiliation https://www.grid.ac/institutes/grid.266102.1
240 schema:familyName Ahituv
241 schema:givenName Nadav
242 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0637155372.91
243 rdf:type schema:Person
244 sg:person.0775731063.54 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
245 schema:familyName Andrie
246 schema:givenName Jennifer M
247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775731063.54
248 rdf:type schema:Person
249 sg:pub.10.1038/clpt.2010.353 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047311871
250 https://doi.org/10.1038/clpt.2010.353
251 rdf:type schema:CreativeWork
252 sg:pub.10.1038/nature07730 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021031479
253 https://doi.org/10.1038/nature07730
254 rdf:type schema:CreativeWork
255 sg:pub.10.1038/nature09534 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010608717
256 https://doi.org/10.1038/nature09534
257 rdf:type schema:CreativeWork
258 sg:pub.10.1038/nature09906 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043304663
259 https://doi.org/10.1038/nature09906
260 rdf:type schema:CreativeWork
261 sg:pub.10.1038/nbt.1589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010374914
262 https://doi.org/10.1038/nbt.1589
263 rdf:type schema:CreativeWork
264 sg:pub.10.1038/ng.2007.55 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053463486
265 https://doi.org/10.1038/ng.2007.55
266 rdf:type schema:CreativeWork
267 sg:pub.10.1038/ng.650 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009136820
268 https://doi.org/10.1038/ng.650
269 rdf:type schema:CreativeWork
270 sg:pub.10.1038/nmeth.1416 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025089276
271 https://doi.org/10.1038/nmeth.1416
272 rdf:type schema:CreativeWork
273 sg:pub.10.1038/nrg3046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044439384
274 https://doi.org/10.1038/nrg3046
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1002/dvdy.22535 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044249979
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1016/s0006-291x(05)80244-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1006684584
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1073/pnas.0903103106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020299353
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1074/jbc.270.37.22058 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015326720
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1074/jbc.270.38.22577 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045309248
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1074/jbc.271.7.3469 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015325852
287 rdf:type schema:CreativeWork
288 https://doi.org/10.1074/jbc.m204047200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035703522
289 rdf:type schema:CreativeWork
290 https://doi.org/10.1086/426833 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049755198
291 rdf:type schema:CreativeWork
292 https://doi.org/10.1089/10430349950017734 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059202919
293 rdf:type schema:CreativeWork
294 https://doi.org/10.1093/nar/gkg585 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025416063
295 rdf:type schema:CreativeWork
296 https://doi.org/10.1101/gr.3577405 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014343625
297 rdf:type schema:CreativeWork
298 https://doi.org/10.1101/gr.6034307 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005155799
299 rdf:type schema:CreativeWork
300 https://doi.org/10.1126/science.1186176 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030603437
301 rdf:type schema:CreativeWork
302 https://doi.org/10.1126/science.288.5463.136 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045941060
303 rdf:type schema:CreativeWork
304 https://doi.org/10.1126/science.2994214 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062580043
305 rdf:type schema:CreativeWork
306 https://doi.org/10.1146/annurev-genom-082509-141651 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034711186
307 rdf:type schema:CreativeWork
308 https://doi.org/10.1371/journal.pbio.1001046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031377769
309 rdf:type schema:CreativeWork
310 https://www.grid.ac/institutes/grid.184769.5 schema:alternateName Lawrence Berkeley National Laboratory
311 schema:name Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California, USA.
312 rdf:type schema:Organization
313 https://www.grid.ac/institutes/grid.266102.1 schema:alternateName University of California, San Francisco
314 schema:name Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
315 rdf:type schema:Organization
316 https://www.grid.ac/institutes/grid.34477.33 schema:alternateName University of Washington
317 schema:name Department of Biostatistics, University of Washington, Seattle, Washington, USA.
318 Department of Computer Science, University of Washington, Seattle, Washington, USA.
319 Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
320 rdf:type schema:Organization
321 https://www.grid.ac/institutes/grid.417691.c schema:alternateName HudsonAlpha Institute for Biotechnology
322 schema:name HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
323 rdf:type schema:Organization
324 https://www.grid.ac/institutes/grid.451309.a schema:alternateName Joint Genome Institute
325 schema:name Department of Energy Joint Genome Institute, Walnut Creek, California, USA.
326 Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California, USA.
327 rdf:type schema:Organization
 




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


...