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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation, and optimization for histone deacetylase inhibitors

Drug Name:Valproic acid;trichostatin A;Suberoylanilide hydroxamic acid;Belinostat;Panobinostat;Entinostat
Drug Category:HDACi
Sample Type:human embryonic stem cells (hESCs)
Condition:healthy
Experiment Type:Expression profiling by array
Experiment Platform:GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Description:We chose a test system of developmental toxicity, related to the generation of neuroectoderm from pluripotent stem cells (UKN1), and exposed cells for 6 days to the histone deacetylase inhibitors (HDACi) valproic acid, trichostatin A, vorinostat, belinostat, panobinostat and entinostat. To provide insight into their toxic action, we identified HDACi consensus genes, assigned them to superordinate biological processes and mapped them to a human transcription factor network constructed from hundreds of transcriptome data sets. A support vector machine (SVM)-based classifier predicted all HDACi correctly. For validation, the classifier was applied to legacy data sets of HDACi, and for each exposure situation, the SVM predictions correlated with the developmental toxicity. Finally, optimization of the classifier based on 100 probe sets showed that eight genes (F2RL2, TFAP2B, EDNRA, FOXD3, SIX3, MT1E, ETS1 and LHX2) are sufficient to separate HDACi from mercurials. Our data demonstrate how human stem cells and transcriptome analysis can be combined for mechanistic grouping and prediction of toxicants. Extension of this concept to mechanisms beyond HDACi would allow prediction of human developmental toxicity hazard of unknown compounds with the UKN1 test system.
PubmedID:26272509
Citation:Rempel E; Hoelting L;Waldmann T;Balmer NV;Schildknecht S;Grinberg M;Das Gaspar JA;Shinde V;Stöber R;Marchan R;van Thriel C;Liebing J;Meisig J;Blüthgen N;Sachinidis A; Rahnenführer J;Hengstler JG;Leist M.A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol2015 Sep;89(9):1599-618.
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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

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