Cho Eunnara, Williams Andrew, Yauk Carole L
Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
Department of Biology, Carleton University, Ottawa, ON, Canada.
Data Brief. 2021 Apr 29;36:107097. doi: 10.1016/j.dib.2021.107097. eCollection 2021 Jun.
Transcriptomic biomarkers facilitate mode of action analysis of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole transcriptome data sets of TK6 human lymphoblastoid cells generated by Templated Oligo-Sequencing (TempO-Seq) after 4 h of exposure to 20 reference compounds (10 HDACi and 10 non-HDACi) [1]. The biomarker, named TGx-HDACi, was derived using the nearest shrunken centroid (NSC) method and can distinguish HDACi from non-HDACi compounds based on the expression pattern across the 81 genes. The classification capability of TGx-HDACi was evaluated by NSC probability analysis of 11 external validation compounds (4 HDACi and 7 non-HDACi) with a probability cut-off of 90%. Thus far, TGx-HDACi has demonstrated 100% accuracy in classifying the reference and validation compounds as HDACi or non-HDACi. Of the 81 TGx-HDACi genes, 19 genes are part of the S1500+ gene panel containing 2753 genes, developed for toxicological assessments [2]. Herein, we assessed the classification performance of the biomarker with this reduced gene set to determine if TGx-HDACi can be applied to analyze S1500+ gene expression profiles. The 20 reference compounds and 11 validation compounds were correctly classified as HDACi or non-HDACi by the NSC probability analysis, principal component analysis, and hierarchical clustering based on the expression of the 19 genes, demonstrating 100% accuracy.
转录组生物标志物通过检测基因表达扰动的特定模式，有助于分析毒物的作用模式。我们使用模板寡核苷酸测序（TempO-Seq）生成的TK6人淋巴母细胞全转录组数据集，在暴露于20种参考化合物（10种组蛋白去乙酰化酶抑制剂和10种非组蛋白去乙酰化酶抑制剂）4小时后，鉴定出一种81基因的组蛋白去乙酰化酶抑制剂（HDACi）转录组生物标志物[1]。该生物标志物名为TGx-HDACi，采用最近收缩质心（NSC）方法得出，可根据81个基因的表达模式将HDACi与非HDACi化合物区分开来。通过对11种外部验证化合物（4种HDACi和7种非HDACi）进行NSC概率分析，以90%的概率截断值评估TGx-HDACi的分类能力。到目前为止，TGx-HDACi在将参考化合物和验证化合物分类为HDACi或非HDACi方面已显示出100%的准确性。在81个TGx-HDACi基因中，有19个基因是为毒理学评估而开发的包含2753个基因的S1500+基因面板的一部分[2]。在此，我们用这个减少的基因集评估了生物标志物的分类性能，以确定TGx-HDACi是否可用于分析S1500+基因表达谱。通过基于19个基因表达的NSC概率分析、主成分分析和层次聚类，20种参考化合物和11种验证化合物被正确分类为HDACi或非HDACi，准确率达100%。
