Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-03

AUTHORS

D M Reif, A A Motsinger-Reif, B A McKinney, M T Rock, J E Crowe, J H Moore

ABSTRACT

Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experimental data. In this study, we apply this paradigm to high-dimensional genetic and proteomic data collected to elucidate the mechanisms underlying the development of adverse events (AEs) in patients after smallpox vaccination. As vaccination was successful in all of the patients under study, the AE outcomes reported likely represent the result of interactions among immune system components that result in excessive or prolonged immune stimulation. In this study, we examined 1442 genetic variables (single nucleotide polymorphisms) and 108 proteomic variables (serum cytokine concentrations) to model AE risk. To accomplish this daunting analytical task, we employed the Random Forests (RF) method to filter the most important attributes, then we used the selected attributes to build a final decision tree model. This strategy is well suited to integrated analysis, as relevant attributes may be selected from categorical or continuous data. Importantly, RF is a natural approach for studying the type of gene-gene, gene-protein and protein-protein interactions we hypothesize to be involved in the development of clinical AEs. RF importance scores for particular attributes take interactions into account, and there may be interactions across data types. Combining information from previous studies on AEs related to smallpox vaccination with the genetic and proteomic attributes identified by RF, we built a comprehensive model of AE development that includes the cytokines intercellular adhesion molecule-1 (ICAM-1 or CD54), interleukin-10 (IL-10), and colony stimulating factor-3 (CSF-3 or G-CSF) and a genetic polymorphism in the cytokine gene interleukin-4 (IL4). The biological factors included in the model support our hypothesized mechanism for the development of AEs involving prolonged stimulation of inflammatory pathways and an imbalance of normal tissue damage repair pathways. This study shows the utility of RF for such analytical tasks, while both enhancing and reinforcing our working model of AE development after smallpox vaccination. More... »

PAGES

gene200880

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gene.2008.80

DOI

http://dx.doi.org/10.1038/gene.2008.80

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053645741

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18923431


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/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biomarkers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cytokines", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Decision Making, Computer-Assisted", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Inflammation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Intercellular Adhesion Molecule-1", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Biological", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Polymorphism, Single Nucleotide", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proteomics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Smallpox Vaccine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Vaccination", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Environmental Protection Agency", 
          "id": "https://www.grid.ac/institutes/grid.418698.a", 
          "name": [
            "National Center for Computational Toxicology, US Environmental Protection Agency, Research Triangle Park, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reif", 
        "givenName": "D M", 
        "id": "sg:person.0763734067.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763734067.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "North Carolina State University", 
          "id": "https://www.grid.ac/institutes/grid.40803.3f", 
          "name": [
            "Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Motsinger-Reif", 
        "givenName": "A A", 
        "id": "sg:person.01010005064.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010005064.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Alabama at Birmingham", 
          "id": "https://www.grid.ac/institutes/grid.265892.2", 
          "name": [
            "Department of Genetics, University of Alabama School of Medicine, Birmingham, AL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "McKinney", 
        "givenName": "B A", 
        "id": "sg:person.01036733601.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01036733601.11"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Vanderbilt University Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.412807.8", 
          "name": [
            "Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rock", 
        "givenName": "M T", 
        "id": "sg:person.01303214116.98", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01303214116.98"
        ], 
        "type": "Person"
      }, 
      {
        "familyName": "Crowe", 
        "givenName": "J E", 
        "id": "sg:person.01310105537.14", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310105537.14"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dartmouth College", 
          "id": "https://www.grid.ac/institutes/grid.254880.3", 
          "name": [
            "Department of Genetics, Dartmouth Medical School, Lebanon, NH, USA", 
            "Computational Genetics Laboratory, Dartmouth Medical School, Lebanon, NH, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Moore", 
        "givenName": "J H", 
        "id": "sg:person.07517464062.70", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07517464062.70"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1586/14789450.1.1.67", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002966484"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2156-5-32", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003496686", 
          "https://doi.org/10.1186/1471-2156-5-32"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd1874", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005300855", 
          "https://doi.org/10.1038/nrd1874"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd1874", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005300855", 
          "https://doi.org/10.1038/nrd1874"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/gepi.20041", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007867684"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bioinformatics/bth457", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008081196"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.170237197", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008823890"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1276", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009927742", 
          "https://doi.org/10.1038/ni1276"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1276", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009927742", 
          "https://doi.org/10.1038/ni1276"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/588670", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013104290"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/jama.292.10.1205", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016652858"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt0402-359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018019913", 
          "https://doi.org/10.1038/nbt0402-359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt0402-359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018019913", 
          "https://doi.org/10.1038/nbt0402-359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/jama.289.24.3290", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018146801"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2353/ajpath.2006.050479", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024174636"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/a:1010933404324", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024739340", 
          "https://doi.org/10.1023/a:1010933404324"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/505503", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024841386"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/b:ifla.0000039560.00231.cd", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027862631", 
          "https://doi.org/10.1023/b:ifla.0000039560.00231.cd"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0047-6374(02)00164-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029067716"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0047-6374(02)00164-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029067716"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1477-5956-2-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031852437", 
          "https://doi.org/10.1186/1477-5956-2-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000099178", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039901892"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-3-540-30115-8_34", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040591284", 
          "https://doi.org/10.1007/978-3-540-30115-8_34"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-3-540-30115-8_34", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040591284", 
          "https://doi.org/10.1007/978-3-540-30115-8_34"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2105-5-147", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042626131", 
          "https://doi.org/10.1186/1471-2105-5-147"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000073735", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043170992"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00041433-200104000-00011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044973078"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00041433-200104000-00011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044973078"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkj151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045730551"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1111/j.1572-0241.2005.40819.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046030423", 
          "https://doi.org/10.1111/j.1572-0241.2005.40819.x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00822942-200605020-00002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046264238", 
          "https://doi.org/10.2165/00822942-200605020-00002"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/505506", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046829630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1145/507338.507355", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046992474"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pgen.0030029", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048315566"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2105-8-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048344717", 
          "https://doi.org/10.1186/1471-2105-8-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0065-2660(01)42028-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049162432"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/382510", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1058674004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2307/1390807", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069468261"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075045794", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4049/jimmunol.170.6.3306", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1075249377"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075765069", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076917908", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2009-03", 
    "datePublishedReg": "2009-03-01", 
    "description": "Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experimental data. In this study, we apply this paradigm to high-dimensional genetic and proteomic data collected to elucidate the mechanisms underlying the development of adverse events (AEs) in patients after smallpox vaccination. As vaccination was successful in all of the patients under study, the AE outcomes reported likely represent the result of interactions among immune system components that result in excessive or prolonged immune stimulation. In this study, we examined 1442 genetic variables (single nucleotide polymorphisms) and 108 proteomic variables (serum cytokine concentrations) to model AE risk. To accomplish this daunting analytical task, we employed the Random Forests (RF) method to filter the most important attributes, then we used the selected attributes to build a final decision tree model. This strategy is well suited to integrated analysis, as relevant attributes may be selected from categorical or continuous data. Importantly, RF is a natural approach for studying the type of gene-gene, gene-protein and protein-protein interactions we hypothesize to be involved in the development of clinical AEs. RF importance scores for particular attributes take interactions into account, and there may be interactions across data types. Combining information from previous studies on AEs related to smallpox vaccination with the genetic and proteomic attributes identified by RF, we built a comprehensive model of AE development that includes the cytokines intercellular adhesion molecule-1 (ICAM-1 or CD54), interleukin-10 (IL-10), and colony stimulating factor-3 (CSF-3 or G-CSF) and a genetic polymorphism in the cytokine gene interleukin-4 (IL4). The biological factors included in the model support our hypothesized mechanism for the development of AEs involving prolonged stimulation of inflammatory pathways and an imbalance of normal tissue damage repair pathways. This study shows the utility of RF for such analytical tasks, while both enhancing and reinforcing our working model of AE development after smallpox vaccination.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/gene.2008.80", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2456704", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2598494", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2424516", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2421417", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1022914", 
        "issn": [
          "1466-4879", 
          "1476-5470"
        ], 
        "name": "Genes & Immunity", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "2", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "10"
      }
    ], 
    "name": "Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination", 
    "pagination": "gene200880", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "ff85950cc2663e8b59d3af757f11cac869cd513da884834b5d92ec8c24510df4"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "18923431"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100953417"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/gene.2008.80"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1053645741"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/gene.2008.80", 
      "https://app.dimensions.ai/details/publication/pub.1053645741"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T19:45", 
    "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_8681_00000426.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/articles/gene200880"
  }
]
 

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/gene.2008.80'

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/gene.2008.80'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/gene.2008.80'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/gene.2008.80'


 

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

293 TRIPLES      21 PREDICATES      78 URIs      34 LITERALS      22 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/gene.2008.80 schema:about N0f92a8bd87664fa4b8bbe1be8b1f65d2
2 N1c4b65a143594325b7d307c8bcbe91ea
3 N2be1e314034549fabb2a33db2ef580f9
4 N2d46498346e3479482252efa5008a6c2
5 N63817a0b72f04aa7ba09782d7eb84f8f
6 N76677502cb18496b9cfe18be7418e7ca
7 N792327bdd87b4a3097081eccf8aaa759
8 Na0690f24a66442d09400c8273054c596
9 Nc3d82a498b214f1b94c3c7a8163e258f
10 Nc7773d25ec9c4c42b5b8f7387b1aa0f2
11 Ne631cb300d854008aa38a0e9ece853f6
12 Nfa695528f6814e60ae6af27222c00d5d
13 Nff67357e3c394f029984db7d470d16cb
14 anzsrc-for:11
15 anzsrc-for:1107
16 schema:author Nbab2e092e1d64058a05c116b86eb504b
17 schema:citation sg:pub.10.1007/978-3-540-30115-8_34
18 sg:pub.10.1023/a:1010933404324
19 sg:pub.10.1023/b:ifla.0000039560.00231.cd
20 sg:pub.10.1038/nbt0402-359
21 sg:pub.10.1038/ni1276
22 sg:pub.10.1038/nrd1874
23 sg:pub.10.1111/j.1572-0241.2005.40819.x
24 sg:pub.10.1186/1471-2105-5-147
25 sg:pub.10.1186/1471-2105-8-5
26 sg:pub.10.1186/1471-2156-5-32
27 sg:pub.10.1186/1477-5956-2-9
28 sg:pub.10.2165/00822942-200605020-00002
29 https://app.dimensions.ai/details/publication/pub.1075045794
30 https://app.dimensions.ai/details/publication/pub.1075765069
31 https://app.dimensions.ai/details/publication/pub.1076917908
32 https://doi.org/10.1001/jama.289.24.3290
33 https://doi.org/10.1001/jama.292.10.1205
34 https://doi.org/10.1002/gepi.20041
35 https://doi.org/10.1016/s0047-6374(02)00164-1
36 https://doi.org/10.1016/s0065-2660(01)42028-1
37 https://doi.org/10.1073/pnas.170237197
38 https://doi.org/10.1086/382510
39 https://doi.org/10.1086/505503
40 https://doi.org/10.1086/505506
41 https://doi.org/10.1086/588670
42 https://doi.org/10.1093/bioinformatics/bth457
43 https://doi.org/10.1093/nar/gkj151
44 https://doi.org/10.1097/00041433-200104000-00011
45 https://doi.org/10.1145/507338.507355
46 https://doi.org/10.1159/000073735
47 https://doi.org/10.1159/000099178
48 https://doi.org/10.1371/journal.pgen.0030029
49 https://doi.org/10.1586/14789450.1.1.67
50 https://doi.org/10.2307/1390807
51 https://doi.org/10.2353/ajpath.2006.050479
52 https://doi.org/10.4049/jimmunol.170.6.3306
53 schema:datePublished 2009-03
54 schema:datePublishedReg 2009-03-01
55 schema:description Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experimental data. In this study, we apply this paradigm to high-dimensional genetic and proteomic data collected to elucidate the mechanisms underlying the development of adverse events (AEs) in patients after smallpox vaccination. As vaccination was successful in all of the patients under study, the AE outcomes reported likely represent the result of interactions among immune system components that result in excessive or prolonged immune stimulation. In this study, we examined 1442 genetic variables (single nucleotide polymorphisms) and 108 proteomic variables (serum cytokine concentrations) to model AE risk. To accomplish this daunting analytical task, we employed the Random Forests (RF) method to filter the most important attributes, then we used the selected attributes to build a final decision tree model. This strategy is well suited to integrated analysis, as relevant attributes may be selected from categorical or continuous data. Importantly, RF is a natural approach for studying the type of gene-gene, gene-protein and protein-protein interactions we hypothesize to be involved in the development of clinical AEs. RF importance scores for particular attributes take interactions into account, and there may be interactions across data types. Combining information from previous studies on AEs related to smallpox vaccination with the genetic and proteomic attributes identified by RF, we built a comprehensive model of AE development that includes the cytokines intercellular adhesion molecule-1 (ICAM-1 or CD54), interleukin-10 (IL-10), and colony stimulating factor-3 (CSF-3 or G-CSF) and a genetic polymorphism in the cytokine gene interleukin-4 (IL4). The biological factors included in the model support our hypothesized mechanism for the development of AEs involving prolonged stimulation of inflammatory pathways and an imbalance of normal tissue damage repair pathways. This study shows the utility of RF for such analytical tasks, while both enhancing and reinforcing our working model of AE development after smallpox vaccination.
56 schema:genre research_article
57 schema:inLanguage en
58 schema:isAccessibleForFree true
59 schema:isPartOf N953a58e642b045bd8bc8a019a2ad7b58
60 Nbd09b49f469f41c19d668fd49498aa48
61 sg:journal.1022914
62 schema:name Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination
63 schema:pagination gene200880
64 schema:productId N42bb27e4d03247f18ef3e7853a6c7fd3
65 N4f66a1f5e2984edda4464dc9ace9777e
66 N7c9739fc6598477b8c5e51310685a436
67 N94448a2cd4034787a43a1f019f631111
68 Na997ac284a3d4cd49a5c8aa6f34afd03
69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053645741
70 https://doi.org/10.1038/gene.2008.80
71 schema:sdDatePublished 2019-04-10T19:45
72 schema:sdLicense https://scigraph.springernature.com/explorer/license/
73 schema:sdPublisher N156db87aafdc40919677230faf319d97
74 schema:url http://www.nature.com/articles/gene200880
75 sgo:license sg:explorer/license/
76 sgo:sdDataset articles
77 rdf:type schema:ScholarlyArticle
78 N0f92a8bd87664fa4b8bbe1be8b1f65d2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
79 schema:name Humans
80 rdf:type schema:DefinedTerm
81 N156db87aafdc40919677230faf319d97 schema:name Springer Nature - SN SciGraph project
82 rdf:type schema:Organization
83 N1c4b65a143594325b7d307c8bcbe91ea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
84 schema:name Cytokines
85 rdf:type schema:DefinedTerm
86 N2be1e314034549fabb2a33db2ef580f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
87 schema:name Female
88 rdf:type schema:DefinedTerm
89 N2d46498346e3479482252efa5008a6c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
90 schema:name Inflammation
91 rdf:type schema:DefinedTerm
92 N413e82f0e6104600b73656a1dcfbe0f8 rdf:first sg:person.01310105537.14
93 rdf:rest Nff4cacfafb3a4622879cfa0a0bb3104b
94 N42bb27e4d03247f18ef3e7853a6c7fd3 schema:name readcube_id
95 schema:value ff85950cc2663e8b59d3af757f11cac869cd513da884834b5d92ec8c24510df4
96 rdf:type schema:PropertyValue
97 N4f66a1f5e2984edda4464dc9ace9777e schema:name nlm_unique_id
98 schema:value 100953417
99 rdf:type schema:PropertyValue
100 N63817a0b72f04aa7ba09782d7eb84f8f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Male
102 rdf:type schema:DefinedTerm
103 N76677502cb18496b9cfe18be7418e7ca schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Smallpox Vaccine
105 rdf:type schema:DefinedTerm
106 N792327bdd87b4a3097081eccf8aaa759 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Biomarkers
108 rdf:type schema:DefinedTerm
109 N798998eee99e4a08aa702d6dde8b85a0 rdf:first sg:person.01303214116.98
110 rdf:rest N413e82f0e6104600b73656a1dcfbe0f8
111 N7c9739fc6598477b8c5e51310685a436 schema:name doi
112 schema:value 10.1038/gene.2008.80
113 rdf:type schema:PropertyValue
114 N94448a2cd4034787a43a1f019f631111 schema:name pubmed_id
115 schema:value 18923431
116 rdf:type schema:PropertyValue
117 N953a58e642b045bd8bc8a019a2ad7b58 schema:issueNumber 2
118 rdf:type schema:PublicationIssue
119 Na0690f24a66442d09400c8273054c596 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Intercellular Adhesion Molecule-1
121 rdf:type schema:DefinedTerm
122 Na997ac284a3d4cd49a5c8aa6f34afd03 schema:name dimensions_id
123 schema:value pub.1053645741
124 rdf:type schema:PropertyValue
125 Nb71ba1041e4b412994a15985cf19c4a8 rdf:first sg:person.01036733601.11
126 rdf:rest N798998eee99e4a08aa702d6dde8b85a0
127 Nbab2e092e1d64058a05c116b86eb504b rdf:first sg:person.0763734067.18
128 rdf:rest Nf49975c4e51942258a7f5595ae0e9606
129 Nbd09b49f469f41c19d668fd49498aa48 schema:volumeNumber 10
130 rdf:type schema:PublicationVolume
131 Nc3d82a498b214f1b94c3c7a8163e258f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Vaccination
133 rdf:type schema:DefinedTerm
134 Nc7773d25ec9c4c42b5b8f7387b1aa0f2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Polymorphism, Single Nucleotide
136 rdf:type schema:DefinedTerm
137 Ne631cb300d854008aa38a0e9ece853f6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Models, Biological
139 rdf:type schema:DefinedTerm
140 Nf49975c4e51942258a7f5595ae0e9606 rdf:first sg:person.01010005064.54
141 rdf:rest Nb71ba1041e4b412994a15985cf19c4a8
142 Nfa695528f6814e60ae6af27222c00d5d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Proteomics
144 rdf:type schema:DefinedTerm
145 Nff4cacfafb3a4622879cfa0a0bb3104b rdf:first sg:person.07517464062.70
146 rdf:rest rdf:nil
147 Nff67357e3c394f029984db7d470d16cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Decision Making, Computer-Assisted
149 rdf:type schema:DefinedTerm
150 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
151 schema:name Medical and Health Sciences
152 rdf:type schema:DefinedTerm
153 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
154 schema:name Immunology
155 rdf:type schema:DefinedTerm
156 sg:grant.2421417 http://pending.schema.org/fundedItem sg:pub.10.1038/gene.2008.80
157 rdf:type schema:MonetaryGrant
158 sg:grant.2424516 http://pending.schema.org/fundedItem sg:pub.10.1038/gene.2008.80
159 rdf:type schema:MonetaryGrant
160 sg:grant.2456704 http://pending.schema.org/fundedItem sg:pub.10.1038/gene.2008.80
161 rdf:type schema:MonetaryGrant
162 sg:grant.2598494 http://pending.schema.org/fundedItem sg:pub.10.1038/gene.2008.80
163 rdf:type schema:MonetaryGrant
164 sg:journal.1022914 schema:issn 1466-4879
165 1476-5470
166 schema:name Genes & Immunity
167 rdf:type schema:Periodical
168 sg:person.01010005064.54 schema:affiliation https://www.grid.ac/institutes/grid.40803.3f
169 schema:familyName Motsinger-Reif
170 schema:givenName A A
171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010005064.54
172 rdf:type schema:Person
173 sg:person.01036733601.11 schema:affiliation https://www.grid.ac/institutes/grid.265892.2
174 schema:familyName McKinney
175 schema:givenName B A
176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01036733601.11
177 rdf:type schema:Person
178 sg:person.01303214116.98 schema:affiliation https://www.grid.ac/institutes/grid.412807.8
179 schema:familyName Rock
180 schema:givenName M T
181 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01303214116.98
182 rdf:type schema:Person
183 sg:person.01310105537.14 schema:familyName Crowe
184 schema:givenName J E
185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310105537.14
186 rdf:type schema:Person
187 sg:person.07517464062.70 schema:affiliation https://www.grid.ac/institutes/grid.254880.3
188 schema:familyName Moore
189 schema:givenName J H
190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07517464062.70
191 rdf:type schema:Person
192 sg:person.0763734067.18 schema:affiliation https://www.grid.ac/institutes/grid.418698.a
193 schema:familyName Reif
194 schema:givenName D M
195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763734067.18
196 rdf:type schema:Person
197 sg:pub.10.1007/978-3-540-30115-8_34 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040591284
198 https://doi.org/10.1007/978-3-540-30115-8_34
199 rdf:type schema:CreativeWork
200 sg:pub.10.1023/a:1010933404324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024739340
201 https://doi.org/10.1023/a:1010933404324
202 rdf:type schema:CreativeWork
203 sg:pub.10.1023/b:ifla.0000039560.00231.cd schema:sameAs https://app.dimensions.ai/details/publication/pub.1027862631
204 https://doi.org/10.1023/b:ifla.0000039560.00231.cd
205 rdf:type schema:CreativeWork
206 sg:pub.10.1038/nbt0402-359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018019913
207 https://doi.org/10.1038/nbt0402-359
208 rdf:type schema:CreativeWork
209 sg:pub.10.1038/ni1276 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009927742
210 https://doi.org/10.1038/ni1276
211 rdf:type schema:CreativeWork
212 sg:pub.10.1038/nrd1874 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005300855
213 https://doi.org/10.1038/nrd1874
214 rdf:type schema:CreativeWork
215 sg:pub.10.1111/j.1572-0241.2005.40819.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1046030423
216 https://doi.org/10.1111/j.1572-0241.2005.40819.x
217 rdf:type schema:CreativeWork
218 sg:pub.10.1186/1471-2105-5-147 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042626131
219 https://doi.org/10.1186/1471-2105-5-147
220 rdf:type schema:CreativeWork
221 sg:pub.10.1186/1471-2105-8-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048344717
222 https://doi.org/10.1186/1471-2105-8-5
223 rdf:type schema:CreativeWork
224 sg:pub.10.1186/1471-2156-5-32 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003496686
225 https://doi.org/10.1186/1471-2156-5-32
226 rdf:type schema:CreativeWork
227 sg:pub.10.1186/1477-5956-2-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031852437
228 https://doi.org/10.1186/1477-5956-2-9
229 rdf:type schema:CreativeWork
230 sg:pub.10.2165/00822942-200605020-00002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046264238
231 https://doi.org/10.2165/00822942-200605020-00002
232 rdf:type schema:CreativeWork
233 https://app.dimensions.ai/details/publication/pub.1075045794 schema:CreativeWork
234 https://app.dimensions.ai/details/publication/pub.1075765069 schema:CreativeWork
235 https://app.dimensions.ai/details/publication/pub.1076917908 schema:CreativeWork
236 https://doi.org/10.1001/jama.289.24.3290 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018146801
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1001/jama.292.10.1205 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016652858
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1002/gepi.20041 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007867684
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1016/s0047-6374(02)00164-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029067716
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1016/s0065-2660(01)42028-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049162432
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1073/pnas.170237197 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008823890
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1086/382510 schema:sameAs https://app.dimensions.ai/details/publication/pub.1058674004
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1086/505503 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024841386
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1086/505506 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046829630
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1086/588670 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013104290
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1093/bioinformatics/bth457 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008081196
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1093/nar/gkj151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045730551
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1097/00041433-200104000-00011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044973078
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1145/507338.507355 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046992474
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1159/000073735 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043170992
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1159/000099178 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039901892
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1371/journal.pgen.0030029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048315566
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1586/14789450.1.1.67 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002966484
271 rdf:type schema:CreativeWork
272 https://doi.org/10.2307/1390807 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069468261
273 rdf:type schema:CreativeWork
274 https://doi.org/10.2353/ajpath.2006.050479 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024174636
275 rdf:type schema:CreativeWork
276 https://doi.org/10.4049/jimmunol.170.6.3306 schema:sameAs https://app.dimensions.ai/details/publication/pub.1075249377
277 rdf:type schema:CreativeWork
278 https://www.grid.ac/institutes/grid.254880.3 schema:alternateName Dartmouth College
279 schema:name Computational Genetics Laboratory, Dartmouth Medical School, Lebanon, NH, USA
280 Department of Genetics, Dartmouth Medical School, Lebanon, NH, USA
281 rdf:type schema:Organization
282 https://www.grid.ac/institutes/grid.265892.2 schema:alternateName University of Alabama at Birmingham
283 schema:name Department of Genetics, University of Alabama School of Medicine, Birmingham, AL, USA
284 rdf:type schema:Organization
285 https://www.grid.ac/institutes/grid.40803.3f schema:alternateName North Carolina State University
286 schema:name Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA
287 rdf:type schema:Organization
288 https://www.grid.ac/institutes/grid.412807.8 schema:alternateName Vanderbilt University Medical Center
289 schema:name Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
290 rdf:type schema:Organization
291 https://www.grid.ac/institutes/grid.418698.a schema:alternateName Environmental Protection Agency
292 schema:name National Center for Computational Toxicology, US Environmental Protection Agency, Research Triangle Park, NC, USA
293 rdf:type schema:Organization
 




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


...