Development of a Dynamic Network Model to Identify Temporal Patterns of Structural Malformations in Zebrafish Embryos Exposed to a Model Toxicant, Tris(4-chlorophenyl)methanol.
Development of a Dynamic Network Model to Identify Temporal Patterns of Structural Malformations in Zebrafish Embryos Exposed to a Model Toxicant, Tris(4-chlorophenyl)methanol.
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DOI：
10.3390/jox13020021
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发表时间：
2023-06-16
影响因子：
6
通讯作者：
George, Uduak Z.
中科院分区：
文献类型：
--
作者：
Schwartz, Ashley V.;Sant, Karilyn E.;George, Uduak Z.
胚胎发生是一个良好协调的过程，依赖于精确的线索和环境信号，直接时空胚胎图案。通常，当这个过程中出现一个错误时，其他错误往往会同时出现。我们认为，随着时间的推移，调查这些异常的共同发生将产生更多的信息，对化学品的毒性模式。在这里，我们使用环境污染物三（4-氯苯基）甲醇（TCPMOH）作为模型毒物，以评估暴露和共发生的发育异常斑马鱼胚胎之间的关系。我们提出了一种动态网络建模方法来研究并发症的异常，包括心包水肿，卵黄囊水肿，颅骨畸形，脊柱畸形，延迟/失败的鱼鳔膨胀，和死亡率TCPMOH暴露引起的。TCPMOH暴露的样本显示异常的共同发生率增加时，与对照组相比。异常被表示为动态网络模型中的节点。使用网络中心性得分来识别随着时间推移具有高共现率的异常。我们发现，暴露组之间的异常共存的时间模式各不相同。特别是高TCPMOH暴露组比低暴露组更早出现异常共现。网络模型还显示，心包和卵黄囊水肿是所有TCPMOH暴露水平中最常见的关键节点，在进一步异常之前。总体而言，本研究引入了一个动态网络模型作为评估发育毒理学的工具，将结构和时间特征与浓度响应相结合。
Embryogenesis is a well-coordinated process relying on precise cues and environmental signals that direct spatiotemporal embryonic patterning. Quite often, when one error in this process occurs, others tend to co-occur. We posit that investigating the co-occurrence of these abnormalities over time would yield additional information about the mode of toxicity for chemicals. Here, we use the environmental contaminant tris(4-chlorophenyl)methanol (TCPMOH) as a model toxicant to assess the relationship between exposures and co-occurrence of developmental abnormalities in zebrafish embryos. We propose a dynamic network modeling approach to study the co-occurrence of abnormalities, including pericardial edema, yolk sac edema, cranial malformation, spinal deformity, delayed/failed swim bladder inflation, and mortality induced by TCPMOH exposure. TCPMOH-exposed samples revealed increased abnormality co-occurrence when compared to controls. The abnormalities were represented as nodes in the dynamic network model. Abnormalities with high co-occurrence over time were identified using network centrality scores. We found that the temporal patterns of abnormality co-occurrence varied between exposure groups. In particular, the high TCPMOH exposure group experienced abnormality co-occurrence earlier than the low exposure group. The network model also revealed that pericardial and yolk sac edema are the most common critical nodes among all TCPMOH exposure levels, preceding further abnormalities. Overall, this study introduces a dynamic network model as a tool for assessing developmental toxicology, integrating structural and temporal features with a concentration response.
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DOI：
10.1007/s00244-003-3008-7
发表时间：
2004-04-01
影响因子：
4
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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