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2022-10-27Zeitschriftenartikel DOI: 10.18452/26457
High Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiation
dc.contributor.authorSeidel, Florian
dc.contributor.authorCherianidou, Anna
dc.contributor.authorKappenberg, Franziska
dc.contributor.authorMarta, Miriam
dc.contributor.authorDreser, Nadine
dc.contributor.authorBlum, Jonathan
dc.contributor.authorWaldmann, Tanja
dc.contributor.authorBlüthgen, Nils
dc.contributor.authorMeisig, Johannes
dc.contributor.authorMadjar, Katrin
dc.contributor.authorHenry, Margit
dc.contributor.authorRotshteyn, Tamara
dc.contributor.authorScholtz-Illigens, Andreas
dc.contributor.authorMarchan, Rosemarie
dc.contributor.authorEdlund, Karolina
dc.contributor.authorLeist, Marcel
dc.contributor.authorRahnenführer, Jörg
dc.contributor.authorSachinidis, Agapios
dc.contributor.authorHengstler, Jan Georg
dc.date.accessioned2023-05-02T08:59:37Z
dc.date.available2023-05-02T08:59:37Z
dc.date.issued2022-10-27none
dc.date.updated2022-12-15T17:44:34Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/27136
dc.description.abstractHuman-relevant tests to predict developmental toxicity are urgently needed. A currently intensively studied approach makes use of differentiating human stem cells to measure chemically-induced deviations of the normal developmental program, as in a recent study based on cardiac differentiation (UKK2). Here, we (i) tested the performance of an assay modeling neuroepithelial differentiation (UKN1), and (ii) explored the benefit of combining assays (UKN1 and UKK2) that model different germ layers. Substance-induced cytotoxicity and genome-wide expression profiles of 23 teratogens and 16 non-teratogens at human-relevant concentrations were generated and used for statistical classification, resulting in accuracies of the UKN1 assay of 87–90%. A comparison to the UKK2 assay (accuracies of 90–92%) showed, in general, a high congruence in compound classification that may be explained by the fact that there was a high overlap of signaling pathways. Finally, the combination of both assays improved the prediction compared to each test alone, and reached accuracies of 92–95%. Although some compounds were misclassified by the individual tests, we conclude that UKN1 and UKK2 can be used for a reliable detection of teratogens in vitro, and that a combined analysis of tests that differentiate hiPSCs into different germ layers and cell types can even further improve the prediction of developmental toxicants.eng
dc.description.sponsorshipSysDT
dc.description.sponsorshipResearch Training Group “Biostatistical Methods for High-Dimensional Data in Toxicology”
dc.description.sponsorshipBMBF (German Ministry of Education and Research) and the DFG (German Research Foundation
dc.description.sponsorshipDK-EPA
dc.description.sponsorshipHorizon 2020
dc.description.sponsorshipHorizon 2020
dc.description.sponsorshipHorizon 2020
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectalternative testing strategieseng
dc.subjectin vitro testeng
dc.subjectinduced pluripotent stem cellseng
dc.subjectdevelopmental and reproductive toxicityeng
dc.subjectdrug screeningeng
dc.subjecttoxicogenomicseng
dc.subjecttranscriptomicseng
dc.subjectgene expressioneng
dc.subject.ddc570 Biologienone
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleHigh Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiationnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/27136-7
dc.identifier.doihttp://dx.doi.org/10.18452/26457
dc.type.versionpublishedVersionnone
local.edoc.pages25none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn2073-4409
dcterms.bibliographicCitation.doi10.3390/cells11213404none
dcterms.bibliographicCitation.journaltitleCellsnone
dcterms.bibliographicCitation.volume11none
dcterms.bibliographicCitation.issue21none
dcterms.bibliographicCitation.articlenumber3404none
dcterms.bibliographicCitation.originalpublishernameMDPInone
dcterms.bibliographicCitation.originalpublisherplaceBaselnone
bua.departmentLebenswissenschaftliche Fakultätnone

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