Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints : Using Public Data to Build Screening Tools within a KNIME Workflow

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2015
Autor:innen
Steinmetz, Fabian P.
Mellor, Claire L.
Cronin, Marc T. D.
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

Assessing compounds for their pharmacological and toxicological properties is of great importance for industry and regulatory agencies. In this study an approach using open source software and open access databases to build screening tools for receptor-mediated effects is presented. The retinoic acid receptor (RAR), as a pharmacologically and toxicologically relevant target, was chosen for this study. RAR agonists are used in the treatment of a number of dermal conditions and specific types of cancer, such as acute promyelocytic leukemia. However, when administered chronically, there is strong evidence that RAR agonists cause hepatosteatosis and liver injury. After compiling information on ligand-protein-interactions, common substructures and physico-chemical properties of ligands were identified manually and coded into SMARTS strings. Based on these SMARTS strings and calculated physico-chemical features, a rule-based screening workflow was built within the KNIME platform. The workflow was evaluated on two datasets: one with RAR agonists exclusively and another large, chemically diverse dataset containing only a few RAR agonists. Possible modifications and applications of screening workflows, dependent on their purpose, are presented.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
004 Informatik
Schlagwörter
Predictive toxicology, Drug discovery, Screening with KNIME, Receptor-mediated toxicity, Retinoids
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690STEINMETZ, Fabian P., Claire L. MELLOR, Thorsten MEINL, Marc T. D. CRONIN, 2015. Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints : Using Public Data to Build Screening Tools within a KNIME Workflow. In: Molecular Informatics. 2015, 34(2-3), pp. 171-178. ISSN 0722-3676. eISSN 1611-0218. Available under: doi: 10.1002/minf.201400188
BibTex
@article{Steinmetz2015Scree-31249,
  year={2015},
  doi={10.1002/minf.201400188},
  title={Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints : Using Public Data to Build Screening Tools within a KNIME Workflow},
  number={2-3},
  volume={34},
  issn={0722-3676},
  journal={Molecular Informatics},
  pages={171--178},
  author={Steinmetz, Fabian P. and Mellor, Claire L. and Meinl, Thorsten and Cronin, Marc T. D.}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/31249">
    <dcterms:abstract xml:lang="eng">Assessing compounds for their pharmacological and toxicological properties is of great importance for industry and regulatory agencies. In this study an approach using open source software and open access databases to build screening tools for receptor-mediated effects is presented. The retinoic acid receptor (RAR), as a pharmacologically and toxicologically relevant target, was chosen for this study. RAR agonists are used in the treatment of a number of dermal conditions and specific types of cancer, such as acute promyelocytic leukemia. However, when administered chronically, there is strong evidence that RAR agonists cause hepatosteatosis and liver injury. After compiling information on ligand-protein-interactions, common substructures and physico-chemical properties of ligands were identified manually and coded into SMARTS strings. Based on these SMARTS strings and calculated physico-chemical features, a rule-based screening workflow was built within the KNIME platform. The workflow was evaluated on two datasets: one with RAR agonists exclusively and another large, chemically diverse dataset containing only a few RAR agonists. Possible modifications and applications of screening workflows, dependent on their purpose, are presented.</dcterms:abstract>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-23T11:46:48Z</dcterms:available>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Meinl, Thorsten</dc:contributor>
    <dc:creator>Cronin, Marc T. D.</dc:creator>
    <dc:contributor>Steinmetz, Fabian P.</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-23T11:46:48Z</dc:date>
    <dc:contributor>Cronin, Marc T. D.</dc:contributor>
    <dcterms:issued>2015</dcterms:issued>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36"/>
    <dc:creator>Mellor, Claire L.</dc:creator>
    <dc:creator>Meinl, Thorsten</dc:creator>
    <dc:language>eng</dc:language>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/31249"/>
    <dc:contributor>Mellor, Claire L.</dc:contributor>
    <dcterms:title>Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints : Using Public Data to Build Screening Tools within a KNIME Workflow</dcterms:title>
    <dc:creator>Steinmetz, Fabian P.</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Diese Publikation teilen