title: An optimized gene set for transcriptomics based neurodevelopmental toxicity prediction in the neural embryonic stem cell test.
abstract: The murine neural embryonic stem cell test (ESTn) is an in vitro model for neurodevelopmental toxicity testing. Recent studies have shown that application of transcriptomics analyses in the ESTn is useful for obtaining more accurate predictions as well as mechanistic insights. Gene expression responses due to stem cell neural differentiation versus toxicant exposure could be distinguished using the Principal Component Analysis based differentiation track algorithm. In this study, we performed a de novo analysis on combined raw data (10 compounds, 19 exposures) from three previous transcriptomics studies to identify an optimized gene set for neurodevelopmental toxicity prediction in the ESTn. By evaluating predictions of 200,000 randomly selected gene sets, we identified genes which significantly contributed to the prediction reliability. A set of 100 genes was obtained, predominantly involved in (neural) development. Further stringency restrictions resulted in a set of 29 genes that allowed for 84% prediction accuracy (area under the curve 94%). We anticipate these gene sets will contribute to further improve ESTn transcriptomics studies aimed at compound risk assessment.
authors: Laboratory for Health Protection Research (GBO), National Institute for Public Health and the Environment, (RIVM), Bilthoven, The Netherlands. Jeroen.Pennings@rivm.nl
authors: Jeroen L A
authors: JL
authors: Pennings
authors: Peter T
authors: PT
authors: Theunissen
authors: Aldert H
authors: AH
authors: Piersma
mesh_terms: D000465:Algorithms; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D030541:Databases, Genetic; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D018675:Toxicity Tests / Q000379:methods*