ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research

Zebrafish is an effective model organism for toxicological investigations due to their tiny size, quick reproduction, and conserved vertebrate biology. As environmental pollutants continue to increase, it becomes challenging to detect all chemical-related hazards using zebrafish models. In silico mo...

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Main Authors: Hung-Lin Kan, Shan-Shan Wang, Chun-Wei Tung
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325010279
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author Hung-Lin Kan
Shan-Shan Wang
Chun-Wei Tung
author_facet Hung-Lin Kan
Shan-Shan Wang
Chun-Wei Tung
author_sort Hung-Lin Kan
collection DOAJ
description Zebrafish is an effective model organism for toxicological investigations due to their tiny size, quick reproduction, and conserved vertebrate biology. As environmental pollutants continue to increase, it becomes challenging to detect all chemical-related hazards using zebrafish models. In silico models can facilitate prioritizing chemicals prior to further experimental evaluations and providing potential underlying mechanisms. Chemical-phenotype inference system for zebrafish (ZFinfer), an enrichment analysis tool that can predict affected endpoints, was developed by integrating chemical-protein interaction data from the Search Tool for Interacting Chemicals (STITCH) database and gene-phenotype annotation data from the Zebrafish Information Network (ZFIN). Currently, 419,328 chemicals, 23,180 zebrafish proteins, and 3,104 phenotypes for zebrafish were curated and included in the system. ZFinfer has been validated using 777 ToxCast chemicals and 51 priority pollutants from the USEPA. The inference results demonstrated a sensitivity of 0.72 in critical morphological endpoints and a 93 % rediscovery rate for known toxicity records in the ECOTOX knowledgebase. Furthermore, the affected endpoints of 5,195 PFAS chemical exposures were inferred to fill data gaps. ZFinfer could be useful to prioritize chemicals that should be further evaluated and may be applicable in drug discovery and environmental chemical hazard prediction.
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spelling doaj-art-ee51fddf487e4c248e88744f3d08f2432025-08-20T03:03:53ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211868210.1016/j.ecoenv.2025.118682ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant researchHung-Lin Kan0Shan-Shan Wang1Chun-Wei Tung2Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan; Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei 10675, Taiwan; Corresponding author.Zebrafish is an effective model organism for toxicological investigations due to their tiny size, quick reproduction, and conserved vertebrate biology. As environmental pollutants continue to increase, it becomes challenging to detect all chemical-related hazards using zebrafish models. In silico models can facilitate prioritizing chemicals prior to further experimental evaluations and providing potential underlying mechanisms. Chemical-phenotype inference system for zebrafish (ZFinfer), an enrichment analysis tool that can predict affected endpoints, was developed by integrating chemical-protein interaction data from the Search Tool for Interacting Chemicals (STITCH) database and gene-phenotype annotation data from the Zebrafish Information Network (ZFIN). Currently, 419,328 chemicals, 23,180 zebrafish proteins, and 3,104 phenotypes for zebrafish were curated and included in the system. ZFinfer has been validated using 777 ToxCast chemicals and 51 priority pollutants from the USEPA. The inference results demonstrated a sensitivity of 0.72 in critical morphological endpoints and a 93 % rediscovery rate for known toxicity records in the ECOTOX knowledgebase. Furthermore, the affected endpoints of 5,195 PFAS chemical exposures were inferred to fill data gaps. ZFinfer could be useful to prioritize chemicals that should be further evaluated and may be applicable in drug discovery and environmental chemical hazard prediction.http://www.sciencedirect.com/science/article/pii/S0147651325010279Chemical-gene-phenotype inferenceEnrichment analysisEnvironmental pollutantIn silico approachPFASZebrafish phenotype ontology
spellingShingle Hung-Lin Kan
Shan-Shan Wang
Chun-Wei Tung
ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
Ecotoxicology and Environmental Safety
Chemical-gene-phenotype inference
Enrichment analysis
Environmental pollutant
In silico approach
PFAS
Zebrafish phenotype ontology
title ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
title_full ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
title_fullStr ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
title_full_unstemmed ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
title_short ZFinfer: A novel chemical-phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
title_sort zfinfer a novel chemical phenotype inference system for zebrafish for filling data gaps in environmental pollutant research
topic Chemical-gene-phenotype inference
Enrichment analysis
Environmental pollutant
In silico approach
PFAS
Zebrafish phenotype ontology
url http://www.sciencedirect.com/science/article/pii/S0147651325010279
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AT shanshanwang zfinferanovelchemicalphenotypeinferencesystemforzebrafishforfillingdatagapsinenvironmentalpollutantresearch
AT chunweitung zfinferanovelchemicalphenotypeinferencesystemforzebrafishforfillingdatagapsinenvironmentalpollutantresearch