KOPS - Das Institutionelle Repositorium der Universität Konstanz

Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity

Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity

Zitieren

Dateien zu dieser Ressource

Prüfsumme: MD5:e2ae8294a4c4af6404cb8bd98a849545

PENDSE, Salil N., Alexandra MAERTENS, Michael ROSENBERG, Dipanwita ROY, Rick A. FASANI, Marguerite M. VANTANGOLI, Samantha J. MADNICK, Kim BOEKELHEIDE, Thomas HARTUNG, Patrick D. MCMULLEN, 2017. Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity. In: Archives of Toxicology. 91(4), pp. 1749-1762. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-016-1824-6

@article{Pendse2017Infor-39142, title={Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity}, year={2017}, doi={10.1007/s00204-016-1824-6}, number={4}, volume={91}, issn={0340-5761}, journal={Archives of Toxicology}, pages={1749--1762}, author={Pendse, Salil N. and Maertens, Alexandra and Rosenberg, Michael and Roy, Dipanwita and Fasani, Rick A. and Vantangoli, Marguerite M. and Madnick, Samantha J. and Boekelheide, Kim and Hartung, Thomas and McMullen, Patrick D.} }

<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/rdf/resource/123456789/39142"> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Fasani, Rick A.</dc:creator> <dcterms:rights rdf:resource="http://nbn-resolving.de/urn:nbn:de:bsz:352-20150914100631302-4485392-8"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/39142/1/Pendse_0-407819.pdf"/> <dc:creator>Vantangoli, Marguerite M.</dc:creator> <dc:contributor>Madnick, Samantha J.</dc:contributor> <dc:creator>Madnick, Samantha J.</dc:creator> <dc:language>eng</dc:language> <dcterms:issued>2017</dcterms:issued> <dc:contributor>Pendse, Salil N.</dc:contributor> <dc:contributor>Hartung, Thomas</dc:contributor> <dc:contributor>McMullen, Patrick D.</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/39142"/> <dc:contributor>Rosenberg, Michael</dc:contributor> <dc:contributor>Boekelheide, Kim</dc:contributor> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/39142/1/Pendse_0-407819.pdf"/> <dc:creator>Boekelheide, Kim</dc:creator> <dc:creator>Rosenberg, Michael</dc:creator> <dc:creator>Pendse, Salil N.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Fasani, Rick A.</dc:contributor> <dc:contributor>Roy, Dipanwita</dc:contributor> <dcterms:abstract xml:lang="eng">The twenty-first century vision for toxicology involves a transition away from high-dose animal studies to in vitro and computational models (NRC in Toxicity testing in the 21st century: a vision and a strategy, The National Academies Press, Washington, DC, 2007). This transition requires mapping pathways of toxicity by understanding how in vitro systems respond to chemical perturbation. Uncovering transcription factors/signaling networks responsible for gene expression patterns is essential for defining pathways of toxicity, and ultimately, for determining the chemical modes of action through which a toxicant acts. Traditionally, transcription factor identification is achieved via chromatin immunoprecipitation studies and summarized by calculating which transcription factors are statistically associated with up- and downregulated genes. These lists are commonly determined via statistical or fold-change cutoffs, a procedure that is sensitive to statistical power and may not be as useful for determining transcription factor associations. To move away from an arbitrary statistical or fold-change-based cutoff, we developed, in the context of the Mapping the Human Toxome project, an enrichment paradigm called information-dependent enrichment analysis (IDEA) to guide identification of the transcription factor network. We used a test case of activation in MCF-7 cells by 17β estradiol (E2). Using this new approach, we established a time course for transcriptional and functional responses to E2. ERα and ERβ were associated with short-term transcriptional changes in response to E2. Sustained exposure led to recruitment of additional transcription factors and alteration of cell cycle machinery. TFAP2C and SOX2 were the transcription factors most highly correlated with dose. E2F7, E2F1, and Foxm1, which are involved in cell proliferation, were enriched only at 24 h. IDEA should be useful for identifying candidate pathways of toxicity. IDEA outperforms gene set enrichment analysis (GSEA) and provides similar results to weighted gene correlation network analysis, a platform that helps to identify genes not annotated to pathways.</dcterms:abstract> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-06-07T08:26:27Z</dc:date> <dc:creator>Hartung, Thomas</dc:creator> <dc:creator>McMullen, Patrick D.</dc:creator> <dc:creator>Maertens, Alexandra</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Vantangoli, Marguerite M.</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-06-07T08:26:27Z</dcterms:available> <dc:contributor>Maertens, Alexandra</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:title>Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity</dcterms:title> <dc:creator>Roy, Dipanwita</dc:creator> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 07.06.2017 (Informationen über die Zugriffsstatistik)

Pendse_0-407819.pdf 42

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto