Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-09-20

AUTHORS

Leila Pirhaji, Pamela Milani, Simona Dalin, Brook T. Wassie, Denise E. Dunn, Robert J. Fenster, Julian Avila-Pacheco, Paul Greengard, Clary B. Clish, Myriam Heiman, Donald C. Lo, Ernest Fraenkel

ABSTRACT

The immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington’s disease patients and controls, identifying and prioritizing phenotype-associated genes. We verify the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington’s disease models. Finally, we show that one consequence of inhibiting SPL is intracellular inhibition of histone deacetylases, thus linking our observations in sphingolipid metabolism to a well-characterized Huntington’s disease pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes. More... »

PAGES

623

References to SciGraph publications

  • 2010-06-17. An update on sphingosine-1-phosphate and other sphingolipid mediators in NATURE CHEMICAL BIOLOGY
  • 2009-02-03. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists in BMC BIOINFORMATICS
  • 2004-09-15. Bioconductor: open software development for computational biology and bioinformatics in GENOME BIOLOGY
  • 2003-08. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis in NATURE
  • 2013-04-25. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions in GENOME BIOLOGY
  • 2016-08-01. Revealing disease-associated pathways by network integration of untargeted metabolomics in NATURE METHODS
  • 2012-03-16. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets in GENOME BIOLOGY
  • 2013-01-17. Histone acetylation: molecular mnemonics on the chromatin in NATURE REVIEWS NEUROSCIENCE
  • 2014-01-27. Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer’s disease in ACTA NEUROPATHOLOGICA COMMUNICATIONS
  • 2006-10-01. Role of Bax and Bak in mitochondrial morphogenesis in NATURE
  • 2010-06-23. Alterations of the Sphingolipid Pathway in Alzheimer’s Disease: New Biomarkers and Treatment Targets? in NEUROMOLECULAR MEDICINE
  • 2008-04-02. Enabling personalized cancer medicine through analysis of gene-expression patterns in NATURE
  • 2012-03-04. Fast gapped-read alignment with Bowtie 2 in NATURE METHODS
  • 2013-08-15. Defining the role of the Bcl-2 family proteins in Huntington’s disease in CELL DEATH & DISEASE
  • 2012-12-09. Differential analysis of gene regulation at transcript resolution with RNA-seq in NATURE BIOTECHNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-00353-6

    DOI

    http://dx.doi.org/10.1038/s41467-017-00353-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091790087

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28931805


    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/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aldehyde-Lyases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Case-Control Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cohort Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Huntington Disease", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neostriatum", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neural Stem Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phenotype", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.116068.8", 
              "name": [
                "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pirhaji", 
            "givenName": "Leila", 
            "id": "sg:person.0654440163.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654440163.01"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.116068.8", 
              "name": [
                "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Milani", 
            "givenName": "Pamela", 
            "id": "sg:person.01310740431.96", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310740431.96"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.116068.8", 
              "name": [
                "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dalin", 
            "givenName": "Simona", 
            "id": "sg:person.01255254214.23", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255254214.23"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.116068.8", 
              "name": [
                "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wassie", 
            "givenName": "Brook T.", 
            "id": "sg:person.010462054303.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010462054303.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA", 
              "id": "http://www.grid.ac/institutes/grid.189509.c", 
              "name": [
                "Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dunn", 
            "givenName": "Denise E.", 
            "id": "sg:person.01125537556.73", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125537556.73"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "McLean Hospital, 115 Mill Street, 02478, Belmont, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.240206.2", 
              "name": [
                "Picower Institute for Learning and Memory, 43 Vassar St, 02139, Cambridge, Massachusetts, USA", 
                "Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA", 
                "McLean Hospital, 115 Mill Street, 02478, Belmont, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fenster", 
            "givenName": "Robert J.", 
            "id": "sg:person.01170260320.97", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01170260320.97"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.66859.34", 
              "name": [
                "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Avila-Pacheco", 
            "givenName": "Julian", 
            "id": "sg:person.013015545665.52", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013015545665.52"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA", 
              "id": "http://www.grid.ac/institutes/grid.134907.8", 
              "name": [
                "Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Greengard", 
            "givenName": "Paul", 
            "id": "sg:person.01336620154.37", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336620154.37"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.66859.34", 
              "name": [
                "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Clish", 
            "givenName": "Clary B.", 
            "id": "sg:person.0764632420.16", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764632420.16"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MIT Department of Brain and Cognitive Sciences, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.116068.8", 
              "name": [
                "Picower Institute for Learning and Memory, 43 Vassar St, 02139, Cambridge, Massachusetts, USA", 
                "Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA", 
                "MIT Department of Brain and Cognitive Sciences, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Heiman", 
            "givenName": "Myriam", 
            "id": "sg:person.0737603320.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737603320.08"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA", 
              "id": "http://www.grid.ac/institutes/grid.189509.c", 
              "name": [
                "Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lo", 
            "givenName": "Donald C.", 
            "id": "sg:person.01114516426.33", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114516426.33"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA", 
              "id": "http://www.grid.ac/institutes/grid.66859.34", 
              "name": [
                "Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA", 
                "Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fraenkel", 
            "givenName": "Ernest", 
            "id": "sg:person.0701112251.99", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0701112251.99"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/cddis.2013.300", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048360993", 
              "https://doi.org/10.1038/cddis.2013.300"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05111", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009398987", 
              "https://doi.org/10.1038/nature05111"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2012-13-3-r16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038552015", 
              "https://doi.org/10.1186/gb-2012-13-3-r16"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2450", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045152751", 
              "https://doi.org/10.1038/nbt.2450"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.392", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022029473", 
              "https://doi.org/10.1038/nchembio.392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature06915", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043830331", 
              "https://doi.org/10.1038/nature06915"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2004-5-10-r80", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018457673", 
              "https://doi.org/10.1186/gb-2004-5-10-r80"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12017-010-8121-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013387297", 
              "https://doi.org/10.1007/s12017-010-8121-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.1923", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006541515", 
              "https://doi.org/10.1038/nmeth.1923"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2013-14-4-r36", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015459845", 
              "https://doi.org/10.1186/gb-2013-14-4-r36"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2105-10-48", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048544728", 
              "https://doi.org/10.1186/1471-2105-10-48"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature01825", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031857008", 
              "https://doi.org/10.1038/nature01825"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/2051-5960-2-12", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035565154", 
              "https://doi.org/10.1186/2051-5960-2-12"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.3940", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029380447", 
              "https://doi.org/10.1038/nmeth.3940"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrn3427", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035691496", 
              "https://doi.org/10.1038/nrn3427"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2017-09-20", 
        "datePublishedReg": "2017-09-20", 
        "description": "The immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington\u2019s disease patients and controls, identifying and prioritizing phenotype-associated genes. We verify the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington\u2019s disease models. Finally, we show that one consequence of inhibiting SPL is intracellular inhibition of histone deacetylases, thus linking our observations in sphingolipid metabolism to a well-characterized Huntington\u2019s disease pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41467-017-00353-6", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2439086", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3932683", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2520647", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1043282", 
            "issn": [
              "2041-1723"
            ], 
            "name": "Nature Communications", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "8"
          }
        ], 
        "keywords": [
          "sphingosine-1-phosphate lyase 1", 
          "disease patients", 
          "clinical measurements", 
          "disease models", 
          "sphingolipid metabolism", 
          "disease pathways", 
          "Huntington's disease patients", 
          "Huntington's disease models", 
          "neuroprotective effects", 
          "new therapies", 
          "clinical information", 
          "large cohort", 
          "disease process", 
          "therapeutic target", 
          "disease severity", 
          "intracellular inhibition", 
          "histone deacetylases", 
          "disease", 
          "transcriptional data", 
          "metabolism", 
          "patients", 
          "therapy", 
          "cohort", 
          "severity", 
          "dysregulation", 
          "phenotype-associated genes", 
          "control", 
          "genes", 
          "inhibition", 
          "deacetylases", 
          "data", 
          "pathway", 
          "target", 
          "current approaches", 
          "role", 
          "measures", 
          "effect", 
          "enzyme", 
          "critical insights", 
          "transcriptomics", 
          "consequences", 
          "classification", 
          "approach", 
          "identifying", 
          "measurements", 
          "public data", 
          "understanding", 
          "information", 
          "observations", 
          "insights", 
          "method", 
          "model", 
          "binary classification", 
          "process", 
          "analytical approach", 
          "repository"
        ], 
        "name": "Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements", 
        "pagination": "623", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1091790087"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41467-017-00353-6"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "28931805"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41467-017-00353-6", 
          "https://app.dimensions.ai/details/publication/pub.1091790087"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-12-01T06:36", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_747.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41467-017-00353-6"
      }
    ]
     

    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/s41467-017-00353-6'

    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/s41467-017-00353-6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-017-00353-6'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-017-00353-6'


     

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

    322 TRIPLES      21 PREDICATES      107 URIs      84 LITERALS      18 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41467-017-00353-6 schema:about N1042dcf06d9449dab0b3b0cc4bc57353
    2 N4cd39535035440669eafcf3cb112962b
    3 N582cf281d4ea4fb3aaa90ca600e2219b
    4 N70cabbc2033c4904ab0f698475c66a34
    5 Naa4002031f8649248c9eeefede16c7d7
    6 Nb2a0451a90774b75a591f5b2433b1554
    7 Nbaa7d1abc93743b0a9d2eaea30a68e3b
    8 Nbf36182ad54c4fd69813c814cca3edbd
    9 Nd6315cd6a12844a3914335d9747ce9a3
    10 Nd8d5a577b9f24b188dde64aeb37472d9
    11 Ndf9d9997680a4ac787493941bd4358cc
    12 anzsrc-for:06
    13 anzsrc-for:0601
    14 schema:author Nc4f5ceb9bcec4c2cb4fc8a7bb3056340
    15 schema:citation sg:pub.10.1007/s12017-010-8121-y
    16 sg:pub.10.1038/cddis.2013.300
    17 sg:pub.10.1038/nature01825
    18 sg:pub.10.1038/nature05111
    19 sg:pub.10.1038/nature06915
    20 sg:pub.10.1038/nbt.2450
    21 sg:pub.10.1038/nchembio.392
    22 sg:pub.10.1038/nmeth.1923
    23 sg:pub.10.1038/nmeth.3940
    24 sg:pub.10.1038/nrn3427
    25 sg:pub.10.1186/1471-2105-10-48
    26 sg:pub.10.1186/2051-5960-2-12
    27 sg:pub.10.1186/gb-2004-5-10-r80
    28 sg:pub.10.1186/gb-2012-13-3-r16
    29 sg:pub.10.1186/gb-2013-14-4-r36
    30 schema:datePublished 2017-09-20
    31 schema:datePublishedReg 2017-09-20
    32 schema:description The immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington’s disease patients and controls, identifying and prioritizing phenotype-associated genes. We verify the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington’s disease models. Finally, we show that one consequence of inhibiting SPL is intracellular inhibition of histone deacetylases, thus linking our observations in sphingolipid metabolism to a well-characterized Huntington’s disease pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes.
    33 schema:genre article
    34 schema:isAccessibleForFree true
    35 schema:isPartOf N036ecab466e744a080c3e936a4766c4e
    36 N2ad49c5e0e094689a978a66a4d74bc85
    37 sg:journal.1043282
    38 schema:keywords Huntington's disease models
    39 Huntington's disease patients
    40 analytical approach
    41 approach
    42 binary classification
    43 classification
    44 clinical information
    45 clinical measurements
    46 cohort
    47 consequences
    48 control
    49 critical insights
    50 current approaches
    51 data
    52 deacetylases
    53 disease
    54 disease models
    55 disease pathways
    56 disease patients
    57 disease process
    58 disease severity
    59 dysregulation
    60 effect
    61 enzyme
    62 genes
    63 histone deacetylases
    64 identifying
    65 information
    66 inhibition
    67 insights
    68 intracellular inhibition
    69 large cohort
    70 measurements
    71 measures
    72 metabolism
    73 method
    74 model
    75 neuroprotective effects
    76 new therapies
    77 observations
    78 pathway
    79 patients
    80 phenotype-associated genes
    81 process
    82 public data
    83 repository
    84 role
    85 severity
    86 sphingolipid metabolism
    87 sphingosine-1-phosphate lyase 1
    88 target
    89 therapeutic target
    90 therapy
    91 transcriptional data
    92 transcriptomics
    93 understanding
    94 schema:name Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements
    95 schema:pagination 623
    96 schema:productId N28c0789bb8f24b8da280c5074c3702d0
    97 N8f05fb9d026244acb961a075e694bf92
    98 Na919a5496dde4976b1eea9f0bf6e2ac9
    99 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091790087
    100 https://doi.org/10.1038/s41467-017-00353-6
    101 schema:sdDatePublished 2022-12-01T06:36
    102 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    103 schema:sdPublisher Na8ed1e1cbaba41a99bcc0a0bd0e89cd9
    104 schema:url https://doi.org/10.1038/s41467-017-00353-6
    105 sgo:license sg:explorer/license/
    106 sgo:sdDataset articles
    107 rdf:type schema:ScholarlyArticle
    108 N036ecab466e744a080c3e936a4766c4e schema:issueNumber 1
    109 rdf:type schema:PublicationIssue
    110 N1042dcf06d9449dab0b3b0cc4bc57353 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    111 schema:name Humans
    112 rdf:type schema:DefinedTerm
    113 N16364255ae3f4924b4907ab8ed65bdf3 rdf:first sg:person.0701112251.99
    114 rdf:rest rdf:nil
    115 N1ac4a8d300da4eeb81f0f67ebe2e3ddc rdf:first sg:person.013015545665.52
    116 rdf:rest N26d19bc54b39443ab5874669cba981a4
    117 N26d19bc54b39443ab5874669cba981a4 rdf:first sg:person.01336620154.37
    118 rdf:rest N4c0b702aa9154498890a65e5076db2d7
    119 N28c0789bb8f24b8da280c5074c3702d0 schema:name dimensions_id
    120 schema:value pub.1091790087
    121 rdf:type schema:PropertyValue
    122 N2ad49c5e0e094689a978a66a4d74bc85 schema:volumeNumber 8
    123 rdf:type schema:PublicationVolume
    124 N3406380b193d4599bf7f43f49ef2b169 rdf:first sg:person.01170260320.97
    125 rdf:rest N1ac4a8d300da4eeb81f0f67ebe2e3ddc
    126 N4ba94eb283e24bd78af9f0bab7a3d0b4 rdf:first sg:person.010462054303.15
    127 rdf:rest Nc19de6a4641a4c8e803a89e6007f799f
    128 N4c0b702aa9154498890a65e5076db2d7 rdf:first sg:person.0764632420.16
    129 rdf:rest Ndb59c1b5e72b4e28966725ea95f80d45
    130 N4cd39535035440669eafcf3cb112962b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Animals
    132 rdf:type schema:DefinedTerm
    133 N4f83bac4ed5e4bda8be50eded17c47ec rdf:first sg:person.01255254214.23
    134 rdf:rest N4ba94eb283e24bd78af9f0bab7a3d0b4
    135 N582cf281d4ea4fb3aaa90ca600e2219b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Cohort Studies
    137 rdf:type schema:DefinedTerm
    138 N70cabbc2033c4904ab0f698475c66a34 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    139 schema:name Mice
    140 rdf:type schema:DefinedTerm
    141 N8e05e0db08fa46d898e0550c0b1b6649 rdf:first sg:person.01310740431.96
    142 rdf:rest N4f83bac4ed5e4bda8be50eded17c47ec
    143 N8f05fb9d026244acb961a075e694bf92 schema:name doi
    144 schema:value 10.1038/s41467-017-00353-6
    145 rdf:type schema:PropertyValue
    146 N978fc0eb21774fabb1c3025b85a67c4d rdf:first sg:person.01114516426.33
    147 rdf:rest N16364255ae3f4924b4907ab8ed65bdf3
    148 Na8ed1e1cbaba41a99bcc0a0bd0e89cd9 schema:name Springer Nature - SN SciGraph project
    149 rdf:type schema:Organization
    150 Na919a5496dde4976b1eea9f0bf6e2ac9 schema:name pubmed_id
    151 schema:value 28931805
    152 rdf:type schema:PropertyValue
    153 Naa4002031f8649248c9eeefede16c7d7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Phenotype
    155 rdf:type schema:DefinedTerm
    156 Nb2a0451a90774b75a591f5b2433b1554 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Huntington Disease
    158 rdf:type schema:DefinedTerm
    159 Nbaa7d1abc93743b0a9d2eaea30a68e3b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Aldehyde-Lyases
    161 rdf:type schema:DefinedTerm
    162 Nbf36182ad54c4fd69813c814cca3edbd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Neostriatum
    164 rdf:type schema:DefinedTerm
    165 Nc19de6a4641a4c8e803a89e6007f799f rdf:first sg:person.01125537556.73
    166 rdf:rest N3406380b193d4599bf7f43f49ef2b169
    167 Nc4f5ceb9bcec4c2cb4fc8a7bb3056340 rdf:first sg:person.0654440163.01
    168 rdf:rest N8e05e0db08fa46d898e0550c0b1b6649
    169 Nd6315cd6a12844a3914335d9747ce9a3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Case-Control Studies
    171 rdf:type schema:DefinedTerm
    172 Nd8d5a577b9f24b188dde64aeb37472d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Male
    174 rdf:type schema:DefinedTerm
    175 Ndb59c1b5e72b4e28966725ea95f80d45 rdf:first sg:person.0737603320.08
    176 rdf:rest N978fc0eb21774fabb1c3025b85a67c4d
    177 Ndf9d9997680a4ac787493941bd4358cc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    178 schema:name Neural Stem Cells
    179 rdf:type schema:DefinedTerm
    180 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    181 schema:name Biological Sciences
    182 rdf:type schema:DefinedTerm
    183 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    184 schema:name Biochemistry and Cell Biology
    185 rdf:type schema:DefinedTerm
    186 sg:grant.2439086 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-017-00353-6
    187 rdf:type schema:MonetaryGrant
    188 sg:grant.2520647 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-017-00353-6
    189 rdf:type schema:MonetaryGrant
    190 sg:grant.3932683 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-017-00353-6
    191 rdf:type schema:MonetaryGrant
    192 sg:journal.1043282 schema:issn 2041-1723
    193 schema:name Nature Communications
    194 schema:publisher Springer Nature
    195 rdf:type schema:Periodical
    196 sg:person.010462054303.15 schema:affiliation grid-institutes:grid.116068.8
    197 schema:familyName Wassie
    198 schema:givenName Brook T.
    199 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010462054303.15
    200 rdf:type schema:Person
    201 sg:person.01114516426.33 schema:affiliation grid-institutes:grid.189509.c
    202 schema:familyName Lo
    203 schema:givenName Donald C.
    204 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114516426.33
    205 rdf:type schema:Person
    206 sg:person.01125537556.73 schema:affiliation grid-institutes:grid.189509.c
    207 schema:familyName Dunn
    208 schema:givenName Denise E.
    209 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125537556.73
    210 rdf:type schema:Person
    211 sg:person.01170260320.97 schema:affiliation grid-institutes:grid.240206.2
    212 schema:familyName Fenster
    213 schema:givenName Robert J.
    214 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01170260320.97
    215 rdf:type schema:Person
    216 sg:person.01255254214.23 schema:affiliation grid-institutes:grid.116068.8
    217 schema:familyName Dalin
    218 schema:givenName Simona
    219 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255254214.23
    220 rdf:type schema:Person
    221 sg:person.013015545665.52 schema:affiliation grid-institutes:grid.66859.34
    222 schema:familyName Avila-Pacheco
    223 schema:givenName Julian
    224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013015545665.52
    225 rdf:type schema:Person
    226 sg:person.01310740431.96 schema:affiliation grid-institutes:grid.116068.8
    227 schema:familyName Milani
    228 schema:givenName Pamela
    229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310740431.96
    230 rdf:type schema:Person
    231 sg:person.01336620154.37 schema:affiliation grid-institutes:grid.134907.8
    232 schema:familyName Greengard
    233 schema:givenName Paul
    234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336620154.37
    235 rdf:type schema:Person
    236 sg:person.0654440163.01 schema:affiliation grid-institutes:grid.116068.8
    237 schema:familyName Pirhaji
    238 schema:givenName Leila
    239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654440163.01
    240 rdf:type schema:Person
    241 sg:person.0701112251.99 schema:affiliation grid-institutes:grid.66859.34
    242 schema:familyName Fraenkel
    243 schema:givenName Ernest
    244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0701112251.99
    245 rdf:type schema:Person
    246 sg:person.0737603320.08 schema:affiliation grid-institutes:grid.116068.8
    247 schema:familyName Heiman
    248 schema:givenName Myriam
    249 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737603320.08
    250 rdf:type schema:Person
    251 sg:person.0764632420.16 schema:affiliation grid-institutes:grid.66859.34
    252 schema:familyName Clish
    253 schema:givenName Clary B.
    254 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764632420.16
    255 rdf:type schema:Person
    256 sg:pub.10.1007/s12017-010-8121-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1013387297
    257 https://doi.org/10.1007/s12017-010-8121-y
    258 rdf:type schema:CreativeWork
    259 sg:pub.10.1038/cddis.2013.300 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048360993
    260 https://doi.org/10.1038/cddis.2013.300
    261 rdf:type schema:CreativeWork
    262 sg:pub.10.1038/nature01825 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031857008
    263 https://doi.org/10.1038/nature01825
    264 rdf:type schema:CreativeWork
    265 sg:pub.10.1038/nature05111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009398987
    266 https://doi.org/10.1038/nature05111
    267 rdf:type schema:CreativeWork
    268 sg:pub.10.1038/nature06915 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043830331
    269 https://doi.org/10.1038/nature06915
    270 rdf:type schema:CreativeWork
    271 sg:pub.10.1038/nbt.2450 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045152751
    272 https://doi.org/10.1038/nbt.2450
    273 rdf:type schema:CreativeWork
    274 sg:pub.10.1038/nchembio.392 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022029473
    275 https://doi.org/10.1038/nchembio.392
    276 rdf:type schema:CreativeWork
    277 sg:pub.10.1038/nmeth.1923 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006541515
    278 https://doi.org/10.1038/nmeth.1923
    279 rdf:type schema:CreativeWork
    280 sg:pub.10.1038/nmeth.3940 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029380447
    281 https://doi.org/10.1038/nmeth.3940
    282 rdf:type schema:CreativeWork
    283 sg:pub.10.1038/nrn3427 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035691496
    284 https://doi.org/10.1038/nrn3427
    285 rdf:type schema:CreativeWork
    286 sg:pub.10.1186/1471-2105-10-48 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048544728
    287 https://doi.org/10.1186/1471-2105-10-48
    288 rdf:type schema:CreativeWork
    289 sg:pub.10.1186/2051-5960-2-12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035565154
    290 https://doi.org/10.1186/2051-5960-2-12
    291 rdf:type schema:CreativeWork
    292 sg:pub.10.1186/gb-2004-5-10-r80 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018457673
    293 https://doi.org/10.1186/gb-2004-5-10-r80
    294 rdf:type schema:CreativeWork
    295 sg:pub.10.1186/gb-2012-13-3-r16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038552015
    296 https://doi.org/10.1186/gb-2012-13-3-r16
    297 rdf:type schema:CreativeWork
    298 sg:pub.10.1186/gb-2013-14-4-r36 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015459845
    299 https://doi.org/10.1186/gb-2013-14-4-r36
    300 rdf:type schema:CreativeWork
    301 grid-institutes:grid.116068.8 schema:alternateName Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA
    302 MIT Department of Brain and Cognitive Sciences, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA
    303 schema:name Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA
    304 Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA
    305 MIT Department of Brain and Cognitive Sciences, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA
    306 Picower Institute for Learning and Memory, 43 Vassar St, 02139, Cambridge, Massachusetts, USA
    307 rdf:type schema:Organization
    308 grid-institutes:grid.134907.8 schema:alternateName Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA
    309 schema:name Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA
    310 rdf:type schema:Organization
    311 grid-institutes:grid.189509.c schema:alternateName Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA
    312 schema:name Center for Drug Discovery, Department of Neurobiology, Duke University Medical Center, 303 Research Drive, 27710, Durham, North Carolina, USA
    313 rdf:type schema:Organization
    314 grid-institutes:grid.240206.2 schema:alternateName McLean Hospital, 115 Mill Street, 02478, Belmont, Massachusetts, USA
    315 schema:name Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University, 1230 York Ave, 10065, New York, New York, USA
    316 McLean Hospital, 115 Mill Street, 02478, Belmont, Massachusetts, USA
    317 Picower Institute for Learning and Memory, 43 Vassar St, 02139, Cambridge, Massachusetts, USA
    318 rdf:type schema:Organization
    319 grid-institutes:grid.66859.34 schema:alternateName Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA
    320 schema:name Broad Institute, 415 Main St, 02142, Cambridge, Massachusetts, USA
    321 Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, Massachusetts, USA
    322 rdf:type schema:Organization
     




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


    ...