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Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques

YUSUF HUSSIEN, Stephen D. Dertinger, George Johnson Orcid Logo

Environmental and Molecular Mutagenesis, Volume: 66, Issue: 3, Pages: 122 - 133

Swansea University Authors: YUSUF HUSSIEN, George Johnson Orcid Logo

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DOI (Published version): 10.1002/em.70003

Abstract

In vitro genotoxicity has historically served a hazard identification role, with simple binary outcomes provided for each of several single endpoint assays. This will need to change, given: (i) efforts to curtail animal testing, (ii) the increased use of multiplexed in vitro assays and the ongoing d...

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Published in: Environmental and Molecular Mutagenesis
ISSN: 0893-6692 1098-2280
Published: Wiley 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa68898
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spelling 2025-04-30T12:27:05.3261374 v2 68898 2025-02-17 Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques c5e624eb2a1820b0e5af65e544b67486 YUSUF HUSSIEN YUSUF HUSSIEN true false 37d0f121db69fd09f364df89e4405e31 0000-0001-5643-9942 George Johnson George Johnson true false 2025-02-17 In vitro genotoxicity has historically served a hazard identification role, with simple binary outcomes provided for each of several single endpoint assays. This will need to change, given: (i) efforts to curtail animal testing, (ii) the increased use of multiplexed in vitro assays and the ongoing development of NAMS, and (iii) the desire to holistically consider quantitative results from multiple biomarkers/endpoints that take potency into consideration. To help facilitate more quantitative analyses of multiple biomarkers and/or assay streams, we explored the combined use of PROAST and Toxicological Prioritization Index (ToxPi) software. As a proofofconcept, this investigation employed the MultiFlow DNA damage assay, focusing on γH2AX and p53 biomarkers at two time points, whereby 10 genotoxicants were evaluated in the presence and absence of rat liver S9 metabolic activation. Whereas PROAST was used to calculate BMD point estimates and confidence intervals (CIs), ToxPi synthesized the BMD results into visual, quantitative summaries conveying genotoxicity and metabolic properties. Our analyses suggest that ToxPi's data synthesis and visualization modules provide useful insights into compound response, chemical grouping, and genotoxic mechanisms. By integrating multiple data sources, we find that ToxPi offers a powerful complementary approach to traditional BMD CI graphs, particularly for the simultaneous analysis of multiple biomarkers, enhancing chemical potency analysis of complex datasets. Journal Article Environmental and Molecular Mutagenesis 66 3 122 133 Wiley 0893-6692 1098-2280 benchmark dose analysis, data visualization, flow cytometry, genotoxicity, hierarchical clustering, ToxPi 13 3 2025 2025-03-13 10.1002/em.70003 COLLEGE NANME COLLEGE CODE Swansea University SU Library paid the OA fee (TA Institutional Deal) This work was supported by Health and Environmental Sciences Institute, HESI GTTC Fast Fund. 2025-04-30T12:27:05.3261374 2025-02-17T09:42:41.2127691 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science YUSUF HUSSIEN 1 Stephen D. Dertinger 2 George Johnson 0000-0001-5643-9942 3 68898__33818__963fe2d13fe34b2e9db1dd59cb98db92.pdf 68898.VOR.pdf 2025-03-14T14:38:31.3754348 Output 666766 application/pdf Version of Record true © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC BY). true eng http://creativecommons.org/licenses/by/4.0/
title Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
spellingShingle Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
YUSUF HUSSIEN
George Johnson
title_short Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
title_full Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
title_fullStr Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
title_full_unstemmed Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
title_sort Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques
author_id_str_mv c5e624eb2a1820b0e5af65e544b67486
37d0f121db69fd09f364df89e4405e31
author_id_fullname_str_mv c5e624eb2a1820b0e5af65e544b67486_***_YUSUF HUSSIEN
37d0f121db69fd09f364df89e4405e31_***_George Johnson
author YUSUF HUSSIEN
George Johnson
author2 YUSUF HUSSIEN
Stephen D. Dertinger
George Johnson
format Journal article
container_title Environmental and Molecular Mutagenesis
container_volume 66
container_issue 3
container_start_page 122
publishDate 2025
institution Swansea University
issn 0893-6692
1098-2280
doi_str_mv 10.1002/em.70003
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
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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
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description In vitro genotoxicity has historically served a hazard identification role, with simple binary outcomes provided for each of several single endpoint assays. This will need to change, given: (i) efforts to curtail animal testing, (ii) the increased use of multiplexed in vitro assays and the ongoing development of NAMS, and (iii) the desire to holistically consider quantitative results from multiple biomarkers/endpoints that take potency into consideration. To help facilitate more quantitative analyses of multiple biomarkers and/or assay streams, we explored the combined use of PROAST and Toxicological Prioritization Index (ToxPi) software. As a proofofconcept, this investigation employed the MultiFlow DNA damage assay, focusing on γH2AX and p53 biomarkers at two time points, whereby 10 genotoxicants were evaluated in the presence and absence of rat liver S9 metabolic activation. Whereas PROAST was used to calculate BMD point estimates and confidence intervals (CIs), ToxPi synthesized the BMD results into visual, quantitative summaries conveying genotoxicity and metabolic properties. Our analyses suggest that ToxPi's data synthesis and visualization modules provide useful insights into compound response, chemical grouping, and genotoxic mechanisms. By integrating multiple data sources, we find that ToxPi offers a powerful complementary approach to traditional BMD CI graphs, particularly for the simultaneous analysis of multiple biomarkers, enhancing chemical potency analysis of complex datasets.
published_date 2025-03-13T05:26:43Z
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