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  1. Article: Reproducibility of organ-level effects in repeat dose animal studies.

    Friedman, Katie Paul / Foster, Miran J / Pham, Ly Ly / Feshuk, Madison / Watford, Sean M / Wambaugh, John F / Judson, Richard S / Setzer, R Woodrow / Thomas, Russell S

    Computational toxicology (Amsterdam, Netherlands)

    2023  Volume 28, Page(s) 1–17

    Abstract: This work estimates benchmarks for new approach method (NAM) performance in predicting organ-level effects in repeat dose studies of adult animals based on variability in replicate animal studies. Treatment-related effect values from the Toxicity ... ...

    Abstract This work estimates benchmarks for new approach method (NAM) performance in predicting organ-level effects in repeat dose studies of adult animals based on variability in replicate animal studies. Treatment-related effect values from the Toxicity Reference database (v2.1) for weight, gross, or histopathological changes in the adrenal gland, liver, kidney, spleen, stomach, and thyroid were used. Rates of chemical concordance among organ-level findings in replicate studies, defined by repeated chemical only, chemical and species, or chemical and study type, were calculated. Concordance was 39 - 88%, depending on organ, and was highest within species. Variance in treatment-related effect values, including lowest effect level (LEL) values and benchmark dose (BMD) values when available, was calculated by organ. Multilinear regression modeling, using study descriptors of organ-level effect values as covariates, was used to estimate total variance, mean square error (MSE), and root residual mean square error (RMSE). MSE values, interpreted as estimates of unexplained variance, suggest study descriptors accounted for 52-69% of total variance in organ-level LELs. RMSE ranged from 0.41 - 0.68 log
    Language English
    Publishing date 2023-06-08
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2468-1113
    ISSN 2468-1113
    DOI 10.1016/j.comtox.2023.100287
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

    Grashow, Rachel G. / De La Rosa, Vanessa Y. / Watford, Sean M. / Ackerman, Janet M. / Rudel, Ruthann A.

    Computational Toxicology. 2017,

    2017  

    Abstract: Targeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part ... ...

    Abstract Targeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part of chemical screening strategies. However, currently available panels do not specifically target biological processes relevant to breast development and carcinogenesis. We have developed a gene panel called the Breast Carcinogen Screen (BCScreen) as a tool to identify potential breast carcinogens and characterize mechanisms of toxicity. First, we used four seminal reviews to identify 14 key characteristics of breast carcinogenesis, such as apoptosis, immunomodulation, and genotoxicity. Then, using a hybrid data and knowledge-driven framework, we systematically combined information from whole transcriptome data from genomic databases, biomedical literature, the CTD chemical-gene interaction database, and primary literature review to generate a panel of 500 genes relevant to breast carcinogenesis. We used normalized pointwise mutual information (NPMI) to rank genes that frequently co-occurred with key characteristics in biomedical literature. We found that many genes identified for BCScreen were not included in prognostic breast cancer or systemic toxicity panels. For example, more than half of BCScreen genes were not included in the Tox21 S1500+ general toxicity gene list. Of the 236 that did overlap between the two panels, representation varied across characteristics of carcinogenesis ranging from 16% for genes associated with growth hormones to 76% for genes associated with xenobiotic metabolism. Enrichment analysis of BCScreen identified pathways and processes including response to steroid hormones, cancer, cell cycle, angiogenesis, DNA damage and breast cancer. The biologically-based systematic approach to gene prioritization demonstrated here provides a flexible framework for creating disease-focused gene panels to support discovery related to etiology. With validation, BCScreen may also be useful for toxicological screening relevant to breast carcinogenesis.
    Keywords Breast cancer ; Chemical carcinogenesis ; Xenoestrogen ; Endocrine disrupting chemical ; Normalized pointwise mutual information
    Language English
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version
    ISSN 2468-1113
    DOI 10.1016/j.comtox.2017.11.003
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Novel application of normalized pointwise mutual information (NPMI) to mine biomedical literature for gene sets associated with disease: use case in breast carcinogenesis.

    Watford, Sean M / Grashow, Rachel G / De La Rosa, Vanessa Y / Rudel, Ruthann A / Friedman, Katie Paul / Martin, Matthew T

    Computational toxicology (Amsterdam, Netherlands)

    2018  Volume 7, Page(s) 46–57

    Abstract: Advances in technology within biomedical sciences have led to an inundation of data across many fields, raising new challenges in how best to integrate and analyze these resources. For example, rapid chemical screening programs like the US Environmental ... ...

    Abstract Advances in technology within biomedical sciences have led to an inundation of data across many fields, raising new challenges in how best to integrate and analyze these resources. For example, rapid chemical screening programs like the US Environmental Protection Agency's ToxCast and the collaborative effort, Tox21, have produced massive amounts of information on putative chemical mechanisms where assay targets are identified as genes; however, systematically linking these hypothesized mechanisms with
    Language English
    Publishing date 2018-06-19
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2468-1113
    ISSN 2468-1113
    DOI 10.1016/j.comtox.2018.06.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

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  4. Article: BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening.

    Grashow, Rachel G / De La Rosa, Vanessa Y / Watford, Sean M / Ackerman, Janet M / Rudel, Ruthann A

    Computational toxicology (Amsterdam, Netherlands)

    2017  Volume 5, Page(s) 16–24

    Abstract: Targeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part ... ...

    Abstract Targeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part of chemical screening strategies. However, currently available panels do not specifically target biological processes relevant to breast development and carcinogenesis. We have developed a gene panel called the Breast Carcinogen Screen (BCScreen) as a tool to identify potential breast carcinogens and characterize mechanisms of toxicity. First, we used four seminal reviews to identify 14 key characteristics of breast carcinogenesis, such as apoptosis, immunomodulation, and genotoxicity. Then, using a hybrid data and knowledge-driven framework, we systematically combined information from whole transcriptome data from genomic databases, biomedical literature, the CTD chemical-gene interaction database, and primary literature review to generate a panel of 500 genes relevant to breast carcinogenesis. We used normalized pointwise mutual information (NPMI) to rank genes that frequently co-occurred with key characteristics in biomedical literature. We found that many genes identified for BCScreen were not included in prognostic breast cancer or systemic toxicity panels. For example, more than half of BCScreen genes were not included in the Tox21 S1500+ general toxicity gene list. Of the 230 that did overlap between the two panels, representation varied across characteristics of carcinogenesis ranging from 21% for genes associated with epigenetics to 82% for genes associated with xenobiotic metabolism. Enrichment analysis of BCScreen identified pathways and processes including response to steroid hormones, cancer, cell cycle, apoptosis, DNA damage and breast cancer. The biologically-based systematic approach to gene prioritization demonstrated here provides a flexible framework for creating disease-focused gene panels to support discovery related to etiology. With validation, BCScreen may also be useful for toxicological screening relevant to breast carcinogenesis.
    Language English
    Publishing date 2017-11-21
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2468-1113
    ISSN 2468-1113
    DOI 10.1016/j.comtox.2017.11.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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