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University of Ottawa

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Environ. Sci. Technol. , Mar 26 2024, | https://doi.org/10.1021/acs.est.3c10543 Empirical Characterization of False Discovery Rates of Differentially Expressed Genes and Transcriptomic Benchmark Concentrations in Zebrafish Embryos

Hyojin Lee ¹, John D H Stead ², Andrew Williams³, Sergio A Cortés Ramírez ⁴, Ella Atlas ³, Jan A Mennigen ¹, Jason M O'Brien ⁵, Carole Yauk¹

¹Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.

²Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.

³Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9, Canada.

⁴Oncogenomics Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico.

⁵Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, Ottawa, Ontario K1A 0H3, Canada.

Corresponding Authors : Jan A. Mennigen, Jason M. O’Brien, Carole Yauk

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-15)
연구진국외 연구진
분야 생명과학 > 분류/생태/환경생물학

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