Development of a Zebrafish S1500+ Sentinel Gene Set for High-Throughput Transcriptomics

Abstract

Sentinel gene sets have been developed with the purpose of maximizing the information from targeted transcriptomic platforms. We recently described the development of an S1500+ sentinel gene set, which was built for the human transcriptome, utilizing a data- and knowledge-driven hybrid approach to select a small subset of genes that optimally capture transcriptional diversity, correlation with other genes based on large-scale expression profiling, and known pathway annotation within the human genome. While this detailed bioinformatics approach for gene selection can in principle be applied to other species, the reliability of the resulting gene set depends on availability of a large body of transcriptomics data. For the model organism zebrafish, we aimed to create a similar sentinel gene set (Zf S1500+ gene set); however, there is insufficient standardized expression data in the public domain to train the gene correlation model. Therefore, our strategy was to use human-zebrafish ortholog mapping of the human S1500+ genes and nominations from experts in the zebrafish scientific community. In this study, we present the bioinformatics curation and refinement process to produce the final Zf S1500+ gene set, explore whole transcriptome extrapolation using this gene set, and assess pathway-level inference. This gene set will add value to targeted high-throughput transcriptomics in zebrafish for toxicogenomic screening and other research domains.

CRISPR Screens in Toxicology Research: An Overview

“…3). Similarly, the S1500+ gene set of toxicology‐related transcripts (Balik‐Meisner et al., 2019; Bushel et al., 2018) could potentially be a useful set for targeted scRNA‐Seq. The individual cellular response of this well‐annotated set of transcripts could provide insights into the role of each targeted gene in response to a toxicant.…”

Translational toxicology in zebrafish

“…Subsequent unbiased pathway-level assessment and gene editing can then be used to solve mode of action in vivo. Unbiased [30e37] or targeted RNA sequencing [38] is routinely used to identify chemical-dependent perturbations in zebrafish at the level of genes and pathways. As an example of the translational potential of this approach, changes in gene expression after exposure to three hepatotoxic compounds were compared across whole zebrafish, mouse and rat livers, in vitro mouse and rat hepatocytes, and primary human hepatocytes [39].…”

Toward Sustainable Environmental Quality: Priority Research Questions for Asia

“…Recently, Zhang et al (2018) proposed a high-throughput functional genomic screening measure in combination with a cell-and a fish embryo-based reduced transcriptomics for mechanistic research on toxicological effects of chemicals. With the reduced gene set for high-throughput transcriptomics, this conceptual framework has promise in addressing mixtures of multiple chemicals, even including hydrophobic chemicals (Vergauwen et al 2015;Balik-Meisner et al 2019). This approach can identify toxicological modes of action of chemicals employing multiple biological organizational levels ranging from the molecular to the cellular and individual (or even community) levels, in a high-throughput manner, which enables grouping of multiple chemicals based on the toxicity pathway or the toxicological modes of action or possible toxicological responses (Xia et al 2020).…”