Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.
Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.
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DOI：
10.1371/journal.pone.0083954
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gong Z
中科院分区：
文献类型：
--
作者：
Liu C;Xu H;Lam SH;Gong Z
越来越明显的是，通过生物标记物监测化学品暴露的困难，因为到目前为止提出的几乎所有生物标记物都不是针对任何个别化学品的。在这项概念验证研究中，成年雄性斑马鱼(Danio Rerio)暴露于5或25µg/L 17β-雌二醇(E2)、100µg/L林丹、5 NM 2，3，7，8-四氯二苯并-对二恶英(TCDD)或15 mg/L砷作用96h，检测了7条途径涉及的59个基因和2个特征良好的生物标志物基因vtg1(卵黄蛋白原1)和cyp1a1(细胞色素P450 1A1)的表达谱。开发了相对距离(RD)计算模型，用于筛选有利基因，并为所选化学物质/浓度的分化生成合适的基因集。我们的结果表明，已知的生物标志物基因并不总是区分药物/浓度对的良好候选基因，其他基因在某些情况下具有更高的潜力。此外，使用不同基因集的表达数据可以获得所检测的5种化学物质/浓度的差异，最好的组合是由50个基因组成的集合；然而，在本试验中，只要两个基因(例如vtg1和hspa5[热休克蛋白5])就足以区分这5种化学物质/浓度组。这些观察结果表明，对于化学暴露的生物监测，多参数阵列应该比传统的生物标志物更可靠，RD计算模型为参数的选择和参数集的生成提供了有效的工具。
It is increasingly evident about the difficulty to monitor chemical exposure through biomarkers as almost all the biomarkers so far proposed are not specific for any individual chemical. In this proof-of-concept study, adult male zebrafish (Danio rerio) were exposed to 5 or 25 µg/L 17β-estradiol (E2), 100 µg/L lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 15 mg/L arsenic for 96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well characterized biomarker genes, vtg1 (vitellogenin1) and cyp1a1 (cytochrome P450 1A1), were examined. Relative distance (RD) computational model was developed to screen favorable genes and generate appropriate gene sets for the differentiation of chemicals/concentrations selected. Our results demonstrated that the known biomarker genes were not always good candidates for the differentiation of pair of chemicals/concentrations, and other genes had higher potentials in some cases. Furthermore, the differentiation of 5 chemicals/concentrations examined were attainable using expression data of various gene sets, and the best combination was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and hspa5 [heat shock protein 5]) were sufficient to differentiate the five chemical/concentration groups in the present test. These observations suggest that multi-parameter arrays should be more reliable for biomonitoring of chemical exposure than traditional biomarkers, and the RD computational model provides an effective tool for the selection of parameters and generation of parameter sets.
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