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Empirical Characterization of False Discovery Rates of Differentially Expressed Genes and Transcriptomic Benchmark Concentrations in Zebrafish Embryos.
Lee, Hyojin; Stead, John D H; Williams, Andrew; Cortés Ramírez, Sergio A; Atlas, Ella; Mennigen, Jan A; O'Brien, Jason M; Yauk, Carole.
Afiliación
  • Lee H; Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
  • Stead JDH; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
  • Williams A; Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9, Canada.
  • Cortés Ramírez SA; Oncogenomics Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico.
  • Atlas E; Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9, Canada.
  • Mennigen JA; Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
  • O'Brien JM; Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, Ottawa, Ontario K1A 0H3, Canada.
  • Yauk C; Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Environ Sci Technol ; 58(14): 6128-6137, 2024 Apr 09.
Article en En | MEDLINE | ID: mdl-38530926
ABSTRACT
High-throughput transcriptomics (HTTr) is increasingly applied to zebrafish embryos to survey the toxicological effects of environmental chemicals. Before the adoption of this approach in regulatory testing, it is essential to characterize background noise in order to guide experimental designs. We thus empirically quantified the HTTr false discovery rate (FDR) across different embryo pool sizes, sample sizes, and concentration groups for toxicology studies. We exposed zebrafish embryos to 0.1% dimethyl sulfoxide (DMSO) for 5 days. Pools of 1, 5, 10, and 20 embryos were created (n = 24 samples for each pool size). Samples were sequenced on the TempO-Seq platform and then randomly assigned to mock treatment groups before differentially expressed gene (DEG), pathway, and benchmark concentration (BMC) analyses. Given that all samples were treated with DMSO, any significant DEGs, pathways, or BMCs are false positives. As expected, we found decreasing FDRs for DEG and pathway analyses with increasing pool and sample sizes. Similarly, FDRs for BMC analyses decreased with increasing pool size and concentration groups, with more stringent BMC premodel filtering reducing BMC FDRs. Our study provides foundational data for determining appropriate experiment designs for regulatory toxicity testing with HTTr in zebrafish embryos.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Dimetilsulfóxido Límite: Animals Idioma: En Revista: Environ Sci Technol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Dimetilsulfóxido Límite: Animals Idioma: En Revista: Environ Sci Technol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos