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An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology / YUSUF HUSSIEN

Swansea University Author: YUSUF HUSSIEN

DOI (Published version): 10.23889/SUthesis.72022

Abstract

Despite the current availability of analytical techniques for genotoxicity studies, limitations in quantitative methods restrict researchers from numerically analysing and explaining how various environmental, chemical, and physical sources cause genetic damage to cells. Benchmark dose serves as an...

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Published: Swansea 2026
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Johnson, George ; Chapman, Kathetine
URI: https://cronfa.swan.ac.uk/Record/cronfa72022
first_indexed 2026-06-08T09:20:58Z
last_indexed 2026-06-09T08:55:12Z
id cronfa72022
recordtype RisThesis
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spelling 2026-06-08T10:45:16.3002338 v2 72022 2026-06-08 An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology c5e624eb2a1820b0e5af65e544b67486 YUSUF HUSSIEN YUSUF HUSSIEN true false 2026-06-08 Despite the current availability of analytical techniques for genotoxicity studies, limitations in quantitative methods restrict researchers from numerically analysing and explaining how various environmental, chemical, and physical sources cause genetic damage to cells. Benchmark dose serves as an important metric when gathering dose-response data from genotoxic compounds and multiple studies assess information on both to appropriately determine doses that result in genetic abnormalities for visualisation, interpretation, and review. The ability to map different compounds according to their genotoxicity allows for the comparative analysis of these compounds to be normalised and formatted in a coherent manner whilst retaining the depth and complexity that they initially had during the processing phase of each dataset. This investigation utilises data generated across multiple tests and assays (Litron Multiflow Genotoxicity Assay, Toxys ToxTracker Assay, TGx-DDI transcriptomic biomarker test, iScreen image analysis and in vitro-to-in vivo extrapolation) to quantitatively measure the genotoxic effects of various mutagenic compounds on cellular biomarkers (e.g. p53, γH2aX. phospho-histone H3, TGx-DDi, Bscl2, CENPA, MPM2, etc) using raw response (imaging induction or fold change/percentage) data generated from multiplexed flow cytometry imaging techniques to expand our understanding of mutagenicity whilst revealing the potential use of data analysis techniques to aid in genetics/cancer research. PROAST was used to calculate benchmark dose confidence intervals (BMD CI) that provide information on potency, and ToxPi was used to analyse the BMD CI across each endpoint and chemical, using approaches such as hierarchical clustering, principal component analysis (PCA) and providing a potency score. In conjunction with a weight-of-evidence approach, this combined analysis will inform us of the chemical grouping and potency across the multiple genetic toxicity endpoints and allow a quicker and more precise assessment of complex datasets. There will be benefits for hazard and risk assessment, while also providing increased weight to in vitro data sets. E-Thesis Swansea Genetic Toxicology, Data Science, Bioinformatics, Genetics, Medicine, Biology, Assays 28 4 2026 2026-04-28 10.23889/SUthesis.72022 ORCiD identifier: https://orcid.org/0009-0004-6023-3663 COLLEGE NANME COLLEGE CODE Swansea University Johnson, George ; Chapman, Kathetine Doctoral Ph.D HESI GTTC Partially funded by HESI GTTC. 2026-06-08T10:45:16.3002338 2026-06-08T10:16:37.0973515 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science YUSUF HUSSIEN 1 72022__36876__e559cdb8465e4aee969d2d2d181c7dd5.pdf Hussien_Yusuf_PhD_Thesis_Final_Cronfa.pdf 2026-06-08T10:40:16.0820931 Output 24562208 application/pdf E-Thesis – open access true Copyright: The Author, Yusuf Hussien, 2026. true eng
title An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
spellingShingle An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
YUSUF HUSSIEN
title_short An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
title_full An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
title_fullStr An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
title_full_unstemmed An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
title_sort An investigation on the Mutagenicity of Compounds using Benchmark Dose and Dose-Response Data for Research in Genetic Toxicology
author_id_str_mv c5e624eb2a1820b0e5af65e544b67486
author_id_fullname_str_mv c5e624eb2a1820b0e5af65e544b67486_***_YUSUF HUSSIEN
author YUSUF HUSSIEN
author2 YUSUF HUSSIEN
format E-Thesis
publishDate 2026
institution Swansea University
doi_str_mv 10.23889/SUthesis.72022
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
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description Despite the current availability of analytical techniques for genotoxicity studies, limitations in quantitative methods restrict researchers from numerically analysing and explaining how various environmental, chemical, and physical sources cause genetic damage to cells. Benchmark dose serves as an important metric when gathering dose-response data from genotoxic compounds and multiple studies assess information on both to appropriately determine doses that result in genetic abnormalities for visualisation, interpretation, and review. The ability to map different compounds according to their genotoxicity allows for the comparative analysis of these compounds to be normalised and formatted in a coherent manner whilst retaining the depth and complexity that they initially had during the processing phase of each dataset. This investigation utilises data generated across multiple tests and assays (Litron Multiflow Genotoxicity Assay, Toxys ToxTracker Assay, TGx-DDI transcriptomic biomarker test, iScreen image analysis and in vitro-to-in vivo extrapolation) to quantitatively measure the genotoxic effects of various mutagenic compounds on cellular biomarkers (e.g. p53, γH2aX. phospho-histone H3, TGx-DDi, Bscl2, CENPA, MPM2, etc) using raw response (imaging induction or fold change/percentage) data generated from multiplexed flow cytometry imaging techniques to expand our understanding of mutagenicity whilst revealing the potential use of data analysis techniques to aid in genetics/cancer research. PROAST was used to calculate benchmark dose confidence intervals (BMD CI) that provide information on potency, and ToxPi was used to analyse the BMD CI across each endpoint and chemical, using approaches such as hierarchical clustering, principal component analysis (PCA) and providing a potency score. In conjunction with a weight-of-evidence approach, this combined analysis will inform us of the chemical grouping and potency across the multiple genetic toxicity endpoints and allow a quicker and more precise assessment of complex datasets. There will be benefits for hazard and risk assessment, while also providing increased weight to in vitro data sets.
published_date 2026-04-28T09:55:12Z
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