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

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 w...

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Main Authors: Ashley V. Schwartz, Karilyn E. Sant, Uduak Z. George
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Journal of Xenobiotics
Subjects:
Online Access:https://www.mdpi.com/2039-4713/13/2/21
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author Ashley V. Schwartz
Karilyn E. Sant
Uduak Z. George
author_facet Ashley V. Schwartz
Karilyn E. Sant
Uduak Z. George
author_sort Ashley V. Schwartz
collection DOAJ
description 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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spelling doaj.art-befa35230c7d482da17a84ef93815f812023-11-18T11:09:58ZengMDPI AGJournal of Xenobiotics2039-47052039-47132023-06-0113228429710.3390/jox13020021Development of a Dynamic Network Model to Identify Temporal Patterns of Structural Malformations in Zebrafish Embryos Exposed to a Model Toxicant, Tris(4-chlorophenyl)methanolAshley V. Schwartz0Karilyn E. Sant1Uduak Z. George2Computational Science Research Center, San Diego State University, San Diego, CA 92182, USASchool of Public Health, Division of Environmental Health, San Diego State University, San Diego, CA 92182, USAComputational Science Research Center, San Diego State University, San Diego, CA 92182, USAEmbryogenesis 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.https://www.mdpi.com/2039-4713/13/2/21embryonic developmentdynamic network modelembryonic morphologytoxicantzebrafish
spellingShingle Ashley V. Schwartz
Karilyn E. Sant
Uduak Z. George
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
Journal of Xenobiotics
embryonic development
dynamic network model
embryonic morphology
toxicant
zebrafish
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic embryonic development
dynamic network model
embryonic morphology
toxicant
zebrafish
url https://www.mdpi.com/2039-4713/13/2/21
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