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  1. Article ; Online: Introducing AOP Reports: Collaborative review and publication of adverse outcome pathways.

    O'Brien, Jason M / Yauk, Carole L

    Environmental and molecular mutagenesis

    2022  Volume 63, Issue 3, Page(s) 116–117

    MeSH term(s) Adverse Outcome Pathways ; Risk Assessment
    Language English
    Publishing date 2022-04-28
    Publishing country United States
    Document type Editorial
    ZDB-ID 639145-x
    ISSN 1098-2280 ; 0893-6692
    ISSN (online) 1098-2280
    ISSN 0893-6692
    DOI 10.1002/em.22481
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  2. Article ; Online: The functional mutational landscape of the

    Beal, Marc A / Meier, Matthew J / Dykes, Angela / Yauk, Carole L / Lambert, Iain B / Marchetti, Francesco

    iScience

    2023  Volume 26, Issue 12, Page(s) 108407

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108407
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  3. Article ; Online: Unlocking the Power of Transcriptomic Biomarkers in Qualitative and Quantitative Genotoxicity Assessment of Chemicals.

    Thienpont, Anouck / Cho, Eunnara / Williams, Andrew / Meier, Matthew J / Yauk, Carole L / Rogiers, Vera / Vanhaecke, Tamara / Mertens, Birgit

    Chemical research in toxicology

    2024  Volume 37, Issue 3, Page(s) 465–475

    Abstract: To modernize genotoxicity assessment and reduce reliance on experimental animals, new approach methodologies (NAMs) that provide human-relevant dose-response data are needed. Two transcriptomic biomarkers, GENOMARK and TGx-DDI, have shown a high ... ...

    Abstract To modernize genotoxicity assessment and reduce reliance on experimental animals, new approach methodologies (NAMs) that provide human-relevant dose-response data are needed. Two transcriptomic biomarkers, GENOMARK and TGx-DDI, have shown a high classification accuracy for genotoxicity. As these biomarkers were extracted from different training sets, we investigated whether combining the two biomarkers in a human-derived metabolically competent cell line (i.e., HepaRG) provides complementary information for the classification of genotoxic hazard identification and potency ranking. First, the applicability of GENOMARK to TempO-Seq, a high-throughput transcriptomic technology, was evaluated. HepaRG cells were exposed for 72 h to increasing concentrations of 10 chemicals (i.e., eight known
    MeSH term(s) Animals ; Humans ; Gene Expression Profiling/methods ; Transcriptome ; Biomarkers ; Cell Line ; DNA Damage
    Chemical Substances Biomarkers
    Language English
    Publishing date 2024-02-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.3c00318
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    Zs.A 2320: Show issues Location:
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  4. Article ; Online: House Dust-Derived Mixtures of Organophosphate Esters Alter the Phenotype, Function, Transcriptome, and Lipidome of KGN Human Ovarian Granulosa Cells.

    Wang, Xiaotong / Rowan-Carroll, Andrea / Meier, Matthew J / Yauk, Carole L / Wade, Michael G / Robaire, Bernard / Hales, Barbara F

    Toxicological sciences : an official journal of the Society of Toxicology

    2024  

    Abstract: Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggest that exposure to OPEs is detrimental to female fertility in humans. However, no experimental information is ... ...

    Abstract Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggest that exposure to OPEs is detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. We used high-content imaging to investigate the effects of environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbations to steroidogenesis were assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq™, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using a cholesterol assay and global lipidomic profiling. OPE mixtures altered multiple phenotypic features of KGN cells, with triaryl OPEs in the mixture showing higher potencies than other mixture components. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Exposure to complex mixtures of OPEs, similar to those found in house dust, may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPEs and highlights the need to examine the effects of human relevant chemical mixtures.
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfae052
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    Zs.A 1709: Show issues Location:
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  5. Article ; Online: A transcriptomic dataset used to derive biomarkers of chemically induced histone deacetylase inhibition (HDACi) in human TK6 cells.

    Cho, Eunnara / Williams, Andrew / Yauk, Carole L

    Data in brief

    2021  Volume 36, Page(s) 107097

    Abstract: Transcriptomic biomarkers facilitate mode of action analysis of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole ... ...

    Abstract Transcriptomic biomarkers facilitate mode of action analysis of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole transcriptome data sets of TK6 human lymphoblastoid cells generated by Templated Oligo-Sequencing (TempO-Seq) after 4 h of exposure to 20 reference compounds (10 HDACi and 10 non-HDACi) [1]. The biomarker, named TGx-HDACi, was derived using the nearest shrunken centroid (NSC) method and can distinguish HDACi from non-HDACi compounds based on the expression pattern across the 81 genes. The classification capability of TGx-HDACi was evaluated by NSC probability analysis of 11 external validation compounds (4 HDACi and 7 non-HDACi) with a probability cut-off of 90%. Thus far, TGx-HDACi has demonstrated 100% accuracy in classifying the reference and validation compounds as HDACi or non-HDACi. Of the 81 TGx-HDACi genes, 19 genes are part of the S1500+ gene panel containing 2753 genes, developed for toxicological assessments [2]. Herein, we assessed the classification performance of the biomarker with this reduced gene set to determine if TGx-HDACi can be applied to analyze S1500+ gene expression profiles. The 20 reference compounds and 11 validation compounds were correctly classified as HDACi or non-HDACi by the NSC probability analysis, principal component analysis, and hierarchical clustering based on the expression of the 19 genes, demonstrating 100% accuracy.
    Language English
    Publishing date 2021-04-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2021.107097
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  6. Article ; Online: Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

    Nelson, Gail M / Carswell, Gleta K / Swartz, Carol D / Recio, Leslie / Yauk, Carole L / Chorley, Brian N

    Toxicology letters

    2023  Volume 384, Page(s) 105–114

    Abstract: To reduce reliance on long-term in vivo studies, short-term data linking early molecular-based measurements to later adverse health effects is needed. Although transcriptional-based benchmark dose ( ... ...

    Abstract To reduce reliance on long-term in vivo studies, short-term data linking early molecular-based measurements to later adverse health effects is needed. Although transcriptional-based benchmark dose (BMD
    MeSH term(s) Mice ; Animals ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Rodentia/genetics ; Liver/metabolism ; Hepatocytes/metabolism ; Furans/toxicity ; Furans/metabolism
    Chemical Substances MicroRNAs ; Furans
    Language English
    Publishing date 2023-07-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2023.07.015
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    Zs.A 1367: Show issues Location:
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  7. Article ; Online: Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.

    Fortin, Anne-Marie V / Long, Alexandra S / Williams, Andrew / Meier, Matthew J / Cox, Julie / Pinsonnault, Claire / Yauk, Carole L / White, Paul A

    Frontiers in toxicology

    2023  Volume 5, Page(s) 1098432

    Abstract: The conventional battery for genotoxicity testing is not well suited to assessing the large number of chemicals needing evaluation. ... ...

    Abstract The conventional battery for genotoxicity testing is not well suited to assessing the large number of chemicals needing evaluation. Traditional
    Language English
    Publishing date 2023-01-23
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-3080
    ISSN (online) 2673-3080
    DOI 10.3389/ftox.2023.1098432
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  8. Article ; Online: A transcriptomic dataset used to derive biomarkers of chemically induced histone deacetylase inhibition (HDACi) in human TK6 cells

    Eunnara Cho / Andrew Williams / Carole L. Yauk

    Data in Brief, Vol 36, Iss , Pp 107097- (2021)

    2021  

    Abstract: Transcriptomic biomarkers facilitate mode of action analysis of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole ... ...

    Abstract Transcriptomic biomarkers facilitate mode of action analysis of toxicants by detecting specific patterns of gene expression perturbations. We identified an 81-gene transcriptomic biomarker of histone deacetylase inhibitors (HDACi) using whole transcriptome data sets of TK6 human lymphoblastoid cells generated by Templated Oligo-Sequencing (TempO-Seq) after 4 h of exposure to 20 reference compounds (10 HDACi and 10 non-HDACi) [1]. The biomarker, named TGx-HDACi, was derived using the nearest shrunken centroid (NSC) method and can distinguish HDACi from non-HDACi compounds based on the expression pattern across the 81 genes. The classification capability of TGx-HDACi was evaluated by NSC probability analysis of 11 external validation compounds (4 HDACi and 7 non-HDACi) with a probability cut-off of 90%. Thus far, TGx-HDACi has demonstrated 100% accuracy in classifying the reference and validation compounds as HDACi or non-HDACi. Of the 81 TGx-HDACi genes, 19 genes are part of the S1500+ gene panel containing 2753 genes, developed for toxicological assessments [2]. Herein, we assessed the classification performance of the biomarker with this reduced gene set to determine if TGx-HDACi can be applied to analyze S1500+ gene expression profiles. The 20 reference compounds and 11 validation compounds were correctly classified as HDACi or non-HDACi by the NSC probability analysis, principal component analysis, and hierarchical clustering based on the expression of the 19 genes, demonstrating 100% accuracy.
    Keywords Transcriptomic biomarker ; Toxicogenomics ; Predictive toxicology ; Histone deacetylase inhibition ; TempO-Seq ; Epigenetics ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
    Subject code 572
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Brief Developmental Exposure to Fluoxetine Causes Life-Long Alteration of the Brain Transcriptome in Zebrafish.

    Nozari, Amin / Gagné, Remi / Lu, Chunyu / Yauk, Carole / Trudeau, Vance L

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 847322

    Abstract: ... transgene to study the effects of developmental daily exposure to FLX (54 µg/L ...

    Abstract Fluoxetine (FLX) and other selective serotonin reuptake inhibitors are widely used to treat depressive disorders during pregnancy. Early-life exposure to FLX is known to disrupt the normal function of the stress axis in humans, rodents, and teleosts. We used a zebrafish line with a cortisol-inducible fluorescent transgene to study the effects of developmental daily exposure to FLX (54 µg/L) on the transcriptomic profile of brain tissues in exposed larvae and later as 6-month-old adults. High throughput RNA sequencing was conducted on brain tissues in unstressed and stressed conditions. Long-lasting effects of FLX were observed in telencephalon (Tel) and hypothalamus (Hyp) of adult zebrafish with 1927 and 5055 genes significantly (≥1.2 fold-change, false-discovery p-value < 0.05) dysregulated in unstressed condition, respectively. Similar findings were observed in Hyp with 1245 and 723 genes being significantly dysregulated in stressed adults, respectively. Differentially expressed genes converted to
    MeSH term(s) Animals ; Brain ; Cholesterol/metabolism ; Epigenesis, Genetic ; Fluoxetine/metabolism ; Fluoxetine/pharmacology ; Transcriptome ; Zebrafish/genetics
    Chemical Substances Fluoxetine (01K63SUP8D) ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-04-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.847322
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  10. Article ; Online: Transcriptome analysis in mouse skin after exposure to ultraviolet radiation from a canopy sunbed.

    Qutob, Sami S / Roesch, Samantha P M / Smiley, Sandy / Bellier, Pascale / Williams, Andrew / Cook, Kate B / Meier, Matthew J / Rowan-Carroll, Andrea / Yauk, Carole L / McNamee, James P

    Photochemistry and photobiology

    2024  

    Abstract: Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R ... ...

    Abstract Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123540-0
    ISSN 1751-1097 ; 0031-8655
    ISSN (online) 1751-1097
    ISSN 0031-8655
    DOI 10.1111/php.13917
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