{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:04:48Z","timestamp":1764587088505,"version":"3.43.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Health"},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R21DK134931-01"],"award-info":[{"award-number":["1R21DK134931-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["K01ES031640"],"award-info":[{"award-number":["K01ES031640"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"College Scientists Foundation"},{"DOI":"10.13039\/100023092","name":"College of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023124","name":"College of Graduate Studies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023124","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Computational Science Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Zebrafish (Danio rerio) are a popular vertebrate model for high-throughput toxicity testing, serving as a model for embryonic development and disease etiology. However, standardized protocols using zebrafish tend to explore pathologies and behaviors at the organism level rather than at the organ-specific level. This study investigates the effects of chemical exposures on pancreatic function in whole-embryo zebrafish by integrating network analysis and machine learning, leveraging widely available datasets to probe an organ-specific effect. We compiled transcriptomics data for zebrafish exposed to 53 exposures from 25 unique chemicals, including halogenated organic compounds, pesticides\/herbicides, endocrine-disrupting chemicals, pharmaceuticals, parabens, and solvents. All raw sequencing data were processed through a uniform bioinformatics pipeline for re-analysis and quality control, identifying differentially expressed genes and altered pathways related to pancreatic function and development. Clustering analysis revealed 5 distinct clusters of chemical exposures with similar impacts on pancreatic pathways, with gene co-expression network analysis identifying key driver genes within these clusters, providing insights into potential biomarkers of chemical-induced pancreatic toxicity. Machine learning was utilized to identify chemical properties that influence pancreatic pathway response, including average mass and biodegradation half-life. The random forest model achieved robust performance (4-fold cross-validation accuracy: 74%) over eXtreme Gradient Boosting, support vector machine, and multiclass logistic regression. This integrative approach enhances our understanding of the relationships between chemical properties and biological responses in a target organ, supporting the use of zebrafish whole embryos as a high-throughput vertebrate model. This computational workflow can be leveraged to investigate the complex effects of other exposures on organ-specific development.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf069","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:15:10Z","timestamp":1747296910000},"page":"330-353","source":"Crossref","is-referenced-by-count":2,"title":["Integrating network analysis and machine learning to elucidate chemical-induced pancreatic toxicity in zebrafish embryos"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2199-1352","authenticated-orcid":false,"given":"Ashley V","family":"Schwartz","sequence":"first","affiliation":[{"name":"Computational Science Research Center, San Diego State University , San Diego, CA 92182,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8565-2072","authenticated-orcid":false,"given":"Karilyn E","family":"Sant","sequence":"additional","affiliation":[{"name":"School of Public Health, San Diego State University , San Diego, CA 92182,","place":["United States"]},{"name":"Department of Pharmacology & Toxicology, Michigan State University , East Lansing, MI 48824,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-3671","authenticated-orcid":false,"given":"Uduak Z","family":"George","sequence":"additional","affiliation":[{"name":"Computational Science Research Center, San Diego State University , San Diego, CA 92182,","place":["United States"]},{"name":"Department of Mathematics and Statistics, San Diego State University , San Diego, CA 92182,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"2025081219530503100_kfaf069-B1","article-title":"Mondoa drives muscle lipid accumulation and insulin resistance","volume":"5","author":"Ahn","year":"2019","journal-title":"JCI Insight"},{"key":"2025081219530503100_kfaf069-B2","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/toxsci\/kfx192","article-title":"Early life exposure to low levels of AHR agonist PCB126 (3,3\u2032,4,4\u2032,5-pentachlorobiphenyl) reprograms gene expression in adult brain","volume":"160","author":"Aluru","year":"2017","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/toxsci\/kfz217","article-title":"Developmental exposure to pcb153 (2,2\u2019,4,4\u2019,5,5\u2019-hexachlorobiphenyl) alters circadian rhythms and the expression of clock and metabolic genes","volume":"173","author":"Aluru","year":"2020","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B4"},{"key":"2025081219530503100_kfaf069-B5","doi-asserted-by":"crossref","first-page":"107141","DOI":"10.1016\/j.jenvrad.2023.107141","article-title":"Insights into the modes of action of tritium on the early-life stages of zebrafish, Danio rerio, using transcriptomic and proteomic analyses","volume":"261","author":"Arcanjo","year":"2023","journal-title":"J Environ Radioact"},{"key":"2025081219530503100_kfaf069-B6","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2025081219530503100_kfaf069-B7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1517\/14740338.2013.741585","article-title":"Examining the safety of PPAR agonists\u2014current trends and future prospects","volume":"12","author":"Bortolini","year":"2013","journal-title":"Expert Opin Drug Saf"},{"key":"2025081219530503100_kfaf069-B8","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/psp4.12009","article-title":"Relating chemical structure to cellular response: an integrative analysis of gene expression, bioactivity, and structural data across 11,000 compounds","volume":"4","author":"Chen","year":"2015","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2025081219530503100_kfaf069-B9","doi-asserted-by":"crossref","first-page":"109702","DOI":"10.1016\/j.envres.2020.109702","article-title":"Calcium signaling as a possible mechanism behind increased locomotor response in zebrafish larvae exposed to a human relevant persistent organic pollutant mixture or PFOS","volume":"187","author":"Christou","year":"2020","journal-title":"Environ Res"},{"key":"2025081219530503100_kfaf069-B10","doi-asserted-by":"crossref","first-page":"10875","DOI":"10.1021\/acs.est.1c02656","article-title":"Revealing adverse outcome pathways from public high-throughput screening data to evaluate new toxicants by a knowledge-based deep neural network approach","volume":"55","author":"Ciallella","year":"2021","journal-title":"Environ Sci Technol"},{"key":"2025081219530503100_kfaf069-B11","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/ieam.1862","article-title":"Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances","volume":"13","author":"Coady","year":"2017","journal-title":"Integr Environ Assess Manag"},{"key":"2025081219530503100_kfaf069-B12","doi-asserted-by":"crossref","first-page":"358029","DOI":"10.1155\/2015\/358029","article-title":"Zebrafish as a model to study the role of peroxisome proliferating-activated receptors in adipogenesis and obesity","volume":"2015","author":"Den Broeder","year":"2015","journal-title":"PPAR Res"},{"key":"2025081219530503100_kfaf069-B13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/toxsci\/kfl103","article-title":"The ToxCast program for prioritizing toxicity testing of environmental chemicals","volume":"95","author":"Dix","year":"2007","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"Star: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2025081219530503100_kfaf069-B15","doi-asserted-by":"crossref","first-page":"109099","DOI":"10.1016\/j.dib.2023.109099","article-title":"In silico microRNA network data in zebrafish after antineoplastic ifosfamide exposure","volume":"48","author":"English","year":"2023","journal-title":"Data Brief"},{"key":"2025081219530503100_kfaf069-B16","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.diabres.2007.01.026","article-title":"Impaired metabolism\u2013secretion coupling in pancreatic \u03b2-cells: role of determinants of mitochondrial ATP production","volume":"77","author":"Fujimoto","year":"2007","journal-title":"Diabetes Res Clin Pract"},{"key":"2025081219530503100_kfaf069-B17","doi-asserted-by":"crossref","first-page":"e49752","DOI":"10.15252\/embr.201949752","article-title":"Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish","volume":"21","author":"Fukuda","year":"2020","journal-title":"EMBO Rep"},{"key":"2025081219530503100_kfaf069-B18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1159\/000213412","article-title":"Pancreatic calcium signaling: role in health and disease","volume":"9","author":"Gomez-Pinilla","year":"2009","journal-title":"Pancreatology"},{"key":"2025081219530503100_kfaf069-B19","doi-asserted-by":"crossref","first-page":"e1009135","DOI":"10.1371\/journal.pcbi.1009135","article-title":"Leveraging high-throughput screening data, deep neural networks, and conditional generative adversarial networks to advance predictive toxicology","volume":"17","author":"Green","year":"2021","journal-title":"PLoS Comput Biol"},{"year":"2008","author":"Hagberg","key":"2025081219530503100_kfaf069-B20"},{"key":"2025081219530503100_kfaf069-B21","first-page":"6696","article-title":"Frequent somatic mutations of the APC gene in human pancreatic cancer","volume":"52","author":"Horii","year":"1992","journal-title":"Cancer Res"},{"key":"2025081219530503100_kfaf069-B22","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"2025081219530503100_kfaf069-B23","doi-asserted-by":"crossref","first-page":"145443","DOI":"10.1016\/j.scitotenv.2021.145443","article-title":"Crosstalk between histological alterations, oxidative stress and immune aberrations of the emerging PFOS alternative OBS in developing zebrafish","volume":"774","author":"Huang","year":"2021","journal-title":"Sci Total Environ"},{"key":"2025081219530503100_kfaf069-B24","doi-asserted-by":"crossref","first-page":"3203161","DOI":"10.1155\/2017\/3203161","article-title":"Mediating roles of ppars in the effects of environmental chemicals on sex steroids","volume":"2017","author":"Huang","year":"2017","journal-title":"PPAR Res"},{"key":"2025081219530503100_kfaf069-B25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/jat.3357","article-title":"The C. elegans model in toxicity testing","volume":"37","author":"Hunt","year":"2017","journal-title":"J Appl Toxicol"},{"key":"2025081219530503100_kfaf069-B26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012776","article-title":"Inferring regulatory networks from expression data using tree-based methods","volume":"5","author":"Huynh-Thu","year":"2010","journal-title":"PLoS One"},{"key":"2025081219530503100_kfaf069-B27","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.chemosphere.2017.12.094","article-title":"Embryonic exposure to mono(2-ethylhexyl) phthalate (MEHP) disrupts pancreatic organogenesis in zebrafish (Danio rerio)","volume":"195","author":"Jacobs","year":"2018","journal-title":"Chemosphere"},{"key":"2025081219530503100_kfaf069-B28","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/08839514.2019.1637138","article-title":"Comparison of performance of data imputation methods for numeric dataset","volume":"33","author":"Jadhav","year":"2019","journal-title":"Appl Artif Intelligence"},{"key":"2025081219530503100_kfaf069-B29","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1289\/ehp.0901392","article-title":"In vitro screening of environmental chemicals for targeted testing prioritization: the toxcast project","volume":"118","author":"Judson","year":"2010","journal-title":"Environ Health Perspect"},{"key":"2025081219530503100_kfaf069-B30","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025081219530503100_kfaf069-B31","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1021\/tx3000939","article-title":"Update on EPA\u2019s ToxCast program: providing high throughput decision support tools for chemical risk management","volume":"25","author":"Kavlock","year":"2012","journal-title":"Chem Res Toxicol"},{"key":"2025081219530503100_kfaf069-B32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2045-3701-2-11","article-title":"Retinoic acid synthesis and functions in early embryonic development","volume":"2","author":"Kin Ting Kam","year":"2012","journal-title":"Cell Biosci"},{"key":"2025081219530503100_kfaf069-B33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/bies.200800123","article-title":"On the diabetic menu: zebrafish as a model for pancreas development and function","volume":"31","author":"Kinkel","year":"2009","journal-title":"Bioessays"},{"key":"2025081219530503100_kfaf069-B34","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.3390\/ijms20246110","article-title":"Calcium signaling in \u00df-cell physiology and pathology: a revisit","volume":"20","author":"Klec","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025081219530503100_kfaf069-B35","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1056\/NEJM198510033131401","article-title":"Retinoic acid embryopathy","volume":"313","author":"Lammer","year":"1985","journal-title":"N Engl J Med"},{"key":"2025081219530503100_kfaf069-B36","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/bioinformatics\/btv694","article-title":"RNA-Enrich: a cut-off free functional enrichment testing method for RNA-seq with improved detection power","volume":"32","author":"Lee","year":"2016","journal-title":"Bioinformatics"},{"key":"2025081219530503100_kfaf069-B37","doi-asserted-by":"crossref","DOI":"10.1002\/9780470400791","volume-title":"Network science: theory and practice","author":"Lewis","year":"2009"},{"key":"2025081219530503100_kfaf069-B38","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"Featurecounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2025081219530503100_kfaf069-B39","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"year":"2017","author":"Lundberg","key":"2025081219530503100_kfaf069-B40"},{"key":"2025081219530503100_kfaf069-B41","first-page":"10","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","author":"Martin","year":"2011"},{"key":"2025081219530503100_kfaf069-B42","doi-asserted-by":"crossref","first-page":"122881","DOI":"10.1016\/j.jhazmat.2020.122881","article-title":"Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis","volume":"398","author":"Mart\u00ednez","year":"2020","journal-title":"J Hazard Mater"},{"key":"2025081219530503100_kfaf069-B43","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.envpol.2018.09.043","article-title":"Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to bisphenol A","volume":"243","author":"Mart\u00ednez","year":"2018","journal-title":"Environ Pollut"},{"key":"2025081219530503100_kfaf069-B44","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.scitotenv.2019.04.200","article-title":"Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos","volume":"674","author":"Mart\u00ednez","year":"2019","journal-title":"Sci Total Environ"},{"key":"2025081219530503100_kfaf069-B45","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/dgd.12565","article-title":"Zebrafish as a model for studying functional pancreatic \u03b2 cells development and regeneration","volume":"60","author":"Matsuda","year":"2018","journal-title":"Dev Growth Differ"},{"key":"2025081219530503100_kfaf069-B46","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/cmb.2008.04TT","article-title":"Bottlenecks and hubs in inferred networks are important for virulence in Salmonella typhimurium","volume":"16","author":"McDermott","year":"2009","journal-title":"J Comput Biol"},{"key":"2025081219530503100_kfaf069-B47","doi-asserted-by":"crossref","first-page":"105815","DOI":"10.1016\/j.aquatox.2021.105815","article-title":"The ecotoxicological contaminant tris(4-chlorophenyl)methanol (TCPMOH) impacts embryonic development in zebrafish (Danio rerio)","volume":"235","author":"Navarrete","year":"2021","journal-title":"Aquat Toxicol"},{"key":"2025081219530503100_kfaf069-B48","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.3389\/fgene.2019.01214","article-title":"Weighted gene co-expression network analysis identifies critical genes in the development of heart failure after acute myocardial infarction","volume":"10","author":"Niu","year":"2019","journal-title":"Front Genet"},{"key":"2025081219530503100_kfaf069-B49","doi-asserted-by":"crossref","first-page":"106584","DOI":"10.1016\/j.cmpb.2021.106584","article-title":"Explanation of machine learning models using shapley additive explanation and application for real data in hospital","volume":"214","author":"Nohara","year":"2022","journal-title":"Comput Methods Programs Biomed"},{"key":"2025081219530503100_kfaf069-B50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ymeth.2013.08.018","article-title":"Zebrafish as a model to study PTPs during development","volume":"65","author":"Paardekooper Overman","year":"2014","journal-title":"Methods"},{"key":"2025081219530503100_kfaf069-B51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/toxsci\/kfab046","article-title":"Transcriptomic changes and the roles of cannabinoid receptors and PPAR\u03b3 in developmental toxicities following exposure to \u03b49-tetrahydrocannabinol and cannabidiol","volume":"182","author":"Pandelides","year":"2021","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B52","doi-asserted-by":"crossref","first-page":"109534","DOI":"10.1016\/j.dib.2023.109534","article-title":"Dataset for diseases associated with exposure to broflanilide, a novel pesticide, in larval zebrafish (Danio rerio)","volume":"50","author":"Patuel","year":"2023","journal-title":"Data Brief"},{"key":"2025081219530503100_kfaf069-B53","doi-asserted-by":"crossref","first-page":"889474","DOI":"10.3389\/fnano.2022.972421","article-title":"Skcv: stratified K-fold cross-validation on ML classifiers for predicting cervical cancer","volume":"4","author":"Prusty","year":"2022","journal-title":"Front Nanotechnol"},{"key":"2025081219530503100_kfaf069-B54","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ntt.2009.06.004","article-title":"Drosophotoxicology: the growing potential for Drosophila in neurotoxicology","volume":"32","author":"Rand","year":"2010","journal-title":"Neurotoxicol Teratol"},{"key":"2025081219530503100_kfaf069-B55","doi-asserted-by":"crossref","first-page":"113027","DOI":"10.1016\/j.envpol.2019.113027","article-title":"The emerging contaminant 3,3'-dichlorobiphenyl (pcb-11) impedes Ahr activation and Cyp1a activity to modify embryotoxicity of Ahr ligands in the zebrafish embryo model (Danio rerio)","volume":"254","author":"Roy","year":"2019","journal-title":"Environ Pollut"},{"key":"2025081219530503100_kfaf069-B56","doi-asserted-by":"crossref","first-page":"116644","DOI":"10.1016\/j.envpol.2021.116644","article-title":"Developmental exposures to perfluorooctanesulfonic acid (PFOS) impact embryonic nutrition, pancreatic morphology, and adiposity in the zebrafish, Danio rerio","volume":"275","author":"Sant","year":"2021","journal-title":"Environ Pollut"},{"key":"2025081219530503100_kfaf069-B57","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.envpol.2016.10.057","article-title":"Embryonic exposures to perfluorooctanesulfonic acid (pfos) disrupt pancreatic organogenesis in the zebrafish, Danio rerio","volume":"220","author":"Sant","year":"2017","journal-title":"Environmental Pollution"},{"key":"2025081219530503100_kfaf069-B58","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/toxics4030020","article-title":"Assessment of toxicological perturbations and variants of pancreatic islet development in the zebrafish model","volume":"4","author":"Sant","year":"2016","journal-title":"Toxics"},{"key":"2025081219530503100_kfaf069-B59","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/toxsci\/kfy237","article-title":"Perfluorobutanesulfonic acid disrupts pancreatic organogenesis and regulation of lipid metabolism in the zebrafish, Danio rerio","volume":"167","author":"Sant","year":"2019","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B60","doi-asserted-by":"crossref","first-page":"108082","DOI":"10.1016\/j.envint.2023.108082","article-title":"New approach methodologies in human regulatory toxicology\u2014not if, but how and when","volume":"178","author":"Schmeisser","year":"2023","journal-title":"Environ Int"},{"key":"2025081219530503100_kfaf069-B61","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/toxsci\/kfx045","article-title":"The transcriptome of the zebrafish embryo after chemical exposure: a meta-analysis","volume":"157","author":"Sch\u00fcttler","year":"2017","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B62","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3390\/jox13020021","article-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","volume":"13","author":"Schwartz","year":"2023","journal-title":"J Xenobiot"},{"key":"2025081219530503100_kfaf069-B63","doi-asserted-by":"crossref","first-page":"vbae065","DOI":"10.1093\/bioadv\/vbae065","article-title":"Danrerlib: a python package for zebrafish transcriptomics","volume":"4","author":"Schwartz","year":"2024","journal-title":"Bioinformatics Advances"},{"key":"2025081219530503100_kfaf069-B64","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1186\/s12864-021-07940-4","article-title":"Gene co-expression network analysis in zebrafish reveals chemical class specific modules","volume":"22","author":"Shankar","year":"2021","journal-title":"BMC Genomics"},{"key":"2025081219530503100_kfaf069-B65","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF02740674","article-title":"Retinoic acid and retinoic acid receptors in development","volume":"10","author":"Sucov","year":"1995","journal-title":"Mol Neurobiol"},{"key":"2025081219530503100_kfaf069-B66","doi-asserted-by":"crossref","first-page":"718072","DOI":"10.3389\/fphar.2022.718072","article-title":"Application of transgenic zebrafish models for studying the effects of estrogenic endocrine disrupting chemicals on embryonic brain development","volume":"13","author":"Takesono","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025081219530503100_kfaf069-B67","doi-asserted-by":"crossref","first-page":"d325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The gene ontology resource: enriching a gold mine","volume":"49","author":"The Gene Ontology Consortium","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025081219530503100_kfaf069-B68","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1289\/ehp.1205784","article-title":"Improving the human hazard characterization of chemicals: a tox21 update","volume":"121","author":"Tice","year":"2013","journal-title":"Environ Health Perspect"},{"key":"2025081219530503100_kfaf069-B69","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cbpc.2015.08.012","article-title":"Deviant development of pancreatic beta cells from embryonic exposure to pcb-126 in zebrafish","volume":"178","author":"Timme-Laragy","year":"2015","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"2025081219530503100_kfaf069-B70","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.mce.2009.04.018","article-title":"Zebrafish pancreas development","volume":"312","author":"Tiso","year":"2009","journal-title":"Mol Cell Endocrinol"},{"key":"2025081219530503100_kfaf069-B71","doi-asserted-by":"crossref","first-page":"115704","DOI":"10.1016\/j.ecoenv.2023.115704","article-title":"Transcriptome analysis reveals differences in developmental neurotoxicity mechanism of methyl-, ethyl-, and propyl- parabens in zebrafish embryos","volume":"268","author":"Tran","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025081219530503100_kfaf069-B72","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.reprotox.2016.05.015","article-title":"Optimizing multi-dimensional high throughput screening using zebrafish","volume":"65","author":"Truong","year":"2016","journal-title":"Reprod Toxicol"},{"key":"2025081219530503100_kfaf069-B73","doi-asserted-by":"crossref","first-page":"R275","DOI":"10.1152\/ajpregu.00180.2009","article-title":"Specific expression and regulation of glucose transporters in zebrafish ionocytes","volume":"297","author":"Tseng","year":"2009","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"year":"2024","author":"US Environmental Protection Agency","key":"2025081219530503100_kfaf069-B74"},{"key":"2025081219530503100_kfaf069-B75","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s12911-019-1004-8","article-title":"Comparing different supervised machine learning algorithms for disease prediction","volume":"19","author":"Uddin","year":"2019","journal-title":"BMC Med Inform Decis Mak"},{"key":"2025081219530503100_kfaf069-B76","doi-asserted-by":"crossref","first-page":"115653","DOI":"10.1016\/j.taap.2021.115653","article-title":"Modulation of PPAR signaling disrupts pancreas development in the zebrafish, Danio rerio","volume":"426","author":"Venezia","year":"2021","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025081219530503100_kfaf069-B77","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"Scipy 1.0: fundamental algorithms for scientific computing in python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nature Methods"},{"key":"2025081219530503100_kfaf069-B78","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1093\/toxsci\/kfx144","article-title":"Characterization of triptolide-induced hepatotoxicity by imaging and transcriptomics in a novel zebrafish model","volume":"159","author":"Vliegenthart","year":"2017","journal-title":"Toxicol Sci"},{"key":"2025081219530503100_kfaf069-B79","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.numecd.2020.01.005","article-title":"Urinary phenols and parabens and diabetes among US adults, NHANES 2005-2014","volume":"30","author":"Ward","year":"2020","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"2025081219530503100_kfaf069-B80","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.156914","article-title":"Embryonic alcohol exposure disrupts the ubiquitin-proteasome system","volume":"7","author":"Weeks","year":"2022","journal-title":"JCI Insight"},{"key":"2025081219530503100_kfaf069-B81","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1515\/hmbci-2015-0052","article-title":"Prenatal exposure to bisphenol A alters mouse fetal pancreatic morphology and islet composition","volume":"25","author":"Whitehead","year":"2016","journal-title":"Horm Mol Biol Clin Investig"},{"key":"2025081219530503100_kfaf069-B82","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13321-017-0247-6","article-title":"The comptox chemistry dashboard: a community data resource for environmental chemistry","volume":"9","author":"Williams","year":"2017","journal-title":"J Cheminform"},{"key":"2025081219530503100_kfaf069-B83","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/bfgp\/elt053","article-title":"The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts","volume":"13","author":"Williams","year":"2014","journal-title":"Brief Funct Genomics"},{"key":"2025081219530503100_kfaf069-B84","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/bdr2.2132","article-title":"Tris(4-chlorophenyl)methane and tris(4-chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos","volume":"115","author":"Wilson","year":"2023","journal-title":"Birth Defects Res"},{"key":"2025081219530503100_kfaf069-B85","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.reprotox.2009.04.013","article-title":"Zebrafish embryos as models for embryotoxic and teratological effects of chemicals","volume":"28","author":"Yang","year":"2009","journal-title":"Reprod Toxicol"},{"key":"2025081219530503100_kfaf069-B86","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ydbio.2005.04.035","article-title":"Exocrine pancreas development in zebrafish","volume":"284","author":"Yee","year":"2005","journal-title":"Dev Biol"},{"key":"2025081219530503100_kfaf069-B87","doi-asserted-by":"crossref","first-page":"108339","DOI":"10.1016\/j.envint.2023.108339","article-title":"Systematic transcriptome-wide meta-analysis across endocrine disrupting chemicals reveals shared and unique liver pathways, gene networks, and disease associations","volume":"183","author":"Zamora","year":"2024","journal-title":"Environ Int"},{"key":"2025081219530503100_kfaf069-B88","doi-asserted-by":"crossref","first-page":"E625","DOI":"10.1152\/ajpendo.00480.2019","article-title":"Stat3 activation induces insulin resistance via a muscle-specific E3 ubiquitin ligase Fbxo40","volume":"318","author":"Zhang","year":"2020","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2025081219530503100_kfaf069-B89","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/bioinformatics\/btw788","article-title":"Metadcn: meta-analysis framework for differential co-expression network detection with an application in breast cancer","volume":"33","author":"Zhu","year":"2017","journal-title":"Bioinformatics"},{"key":"2025081219530503100_kfaf069-B90","doi-asserted-by":"crossref","first-page":"23074","DOI":"10.1038\/srep23074","article-title":"Metabolic role of dipeptidyl peptidase 4 (DPP4) in primary human (pre)adipocytes","volume":"6","author":"Zille\u00dfen","year":"2016","journal-title":"Sci Rep"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfaf069\/63199353\/kfaf069.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/206\/2\/330\/63199353\/kfaf069.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/206\/2\/330\/63199353\/kfaf069.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T23:53:23Z","timestamp":1755042803000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/206\/2\/330\/8133264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":90,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,5,15]]},"published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfaf069","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"type":"print","value":"1096-6080"},{"type":"electronic","value":"1096-0929"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,5,15]]}}}