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  1. Book ; Online: Providing Error Detection for Deep Learning Image Classifiers Using Self-Explainability

    Karimi, Mohammad Mahdi / Heidarshenas, Azin / Edmonson, William W.

    2022  

    Abstract: This paper proposes a self-explainable Deep Learning (SE-DL) system for an image classification problem that performs self-error detection. The self-error detection is key to improving the DL system's safe operation, especially in safety-critical ... ...

    Abstract This paper proposes a self-explainable Deep Learning (SE-DL) system for an image classification problem that performs self-error detection. The self-error detection is key to improving the DL system's safe operation, especially in safety-critical applications such as automotive systems. A SE-DL system outputs both the class prediction and an explanation for that prediction, which provides insight into how the system makes its predictions for humans. Additionally, we leverage the explanation of the proposed SE-DL system to detect potential class prediction errors of the system. The proposed SE-DL system uses a set of concepts to generate the explanation. The concepts are human-understandable lower-level image features in each input image relevant to the higher-level class of that image. We present a concept selection methodology for scoring all concepts and selecting a subset of them based on their contribution to the error detection performance of the proposed SE-DL system. Finally, we present different error detection schemes using the proposed SE-DL system to compare them against an error detection scheme without any SE-DL system.
    Keywords Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Machine Learning
    Subject code 006
    Publishing date 2022-10-15
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mouse HP1γ regulates TRF1 expression and telomere stability.

    Stylianakis, Emmanouil / Chan, Jackson Ping Kei / Law, Pui Pik / Jiang, Yi / Khadayate, Sanjay / Karimi, Mohammad Mahdi / Festenstein, Richard / Vannier, Jean-Baptiste

    Life sciences

    2023  Volume 331, Page(s) 122030

    Abstract: Aims: Telomeric repeat-containing RNAs are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of members of the heterochromatin protein 1 (HP1) ...

    Abstract Aims: Telomeric repeat-containing RNAs are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of members of the heterochromatin protein 1 (HP1) protein family of epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1γ is enriched on gene bodies of actively transcribed human and mouse genes, it is unclear if its transcriptional role is important for HP1γ function in telomere cohesion and telomere maintenance. We aimed to study the effect of mouse HP1γ on the transcription of telomere factors and molecules that can affect telomere maintenance.
    Main methods: We investigated the telomere function of HP1γ by using HP1γ deficient mouse embryonic fibroblasts (MEFs). We used gene expression analysis of HP1γ deficient MEFs and validated the molecular and mechanistic consequences of HP1γ loss by telomere FISH, immunofluorescence, RT-qPCR and DNA-RNA immunoprecipitation (DRIP).
    Key findings: Loss of HP1γ in primary MEFs led to a downregulation of various telomere and telomere-accessory transcripts, including the shelterin protein TRF1. Its downregulation is associated with increased telomere replication stress and DNA damage (γH2AX), effects more profound in females. We suggest that the source for the impaired telomere maintenance is a consequence of increased telomeric DNA-RNA hybrids and TERRAs arising at and from mouse chromosomes 18 and X.
    Significance: Our results suggest an important transcriptional control by mouse HP1γ of various telomere factors including TRF1 protein and TERRAs that has profound consequences on telomere stability, with a potential sexually dimorphic nature.
    MeSH term(s) Animals ; Humans ; Mice ; Chromatin ; DNA ; Fibroblasts/metabolism ; RNA/genetics ; RNA/metabolism ; Telomere/genetics ; Telomere/metabolism ; Transcription Factors/genetics ; Telomeric Repeat Binding Protein 1/metabolism
    Chemical Substances Chromatin ; DNA (9007-49-2) ; RNA (63231-63-0) ; Transcription Factors ; Cbx3 protein, mouse ; Telomeric Repeat Binding Protein 1
    Language English
    Publishing date 2023-08-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2023.122030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mouse HP1γ regulates TRF1 expression and telomere stability

    Stylianakis, Emmanouil / Chan, Jackson Ping Kei / Law, Pui Pik / Jiang, Yi / Khadayate, Sanjay / Karimi, Mohammad Mahdi / Festenstein, Richard / Vannier, Jean-Baptiste

    Life Sciences. 2023 Oct., v. 331 p.122030-

    2023  

    Abstract: Telomeric repeat-containing RNAs are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of members of the heterochromatin protein 1 (HP1) ... ...

    Abstract Telomeric repeat-containing RNAs are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of members of the heterochromatin protein 1 (HP1) protein family of epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1γ is enriched on gene bodies of actively transcribed human and mouse genes, it is unclear if its transcriptional role is important for HP1γ function in telomere cohesion and telomere maintenance. We aimed to study the effect of mouse HP1γ on the transcription of telomere factors and molecules that can affect telomere maintenance. We investigated the telomere function of HP1γ by using HP1γ deficient mouse embryonic fibroblasts (MEFs). We used gene expression analysis of HP1γ deficient MEFs and validated the molecular and mechanistic consequences of HP1γ loss by telomere FISH, immunofluorescence, RT-qPCR and DNA-RNA immunoprecipitation (DRIP). Loss of HP1γ in primary MEFs led to a downregulation of various telomere and telomere-accessory transcripts, including the shelterin protein TRF1. Its downregulation is associated with increased telomere replication stress and DNA damage (γH2AX), effects more profound in females. We suggest that the source for the impaired telomere maintenance is a consequence of increased telomeric DNA-RNA hybrids and TERRAs arising at and from mouse chromosomes 18 and X. Our results suggest an important transcriptional control by mouse HP1γ of various telomere factors including TRF1 protein and TERRAs that has profound consequences on telomere stability, with a potential sexually dimorphic nature.
    Keywords DNA damage ; cohesion ; epigenetics ; fibroblasts ; fish ; fluorescent antibody technique ; gene expression ; genes ; heterochromatin ; humans ; mice ; precipitin tests ; sexual dimorphism ; telomeres ; transcription (genetics) ; Telomere ; HP1 ; Chromatin ; TERRA
    Language English
    Dates of publication 2023-10
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2023.122030
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: CpG Islands Shape the Epigenome Landscape.

    Papin, Christophe / Le Gras, Stéphanie / Ibrahim, Abdulkhaleg / Salem, Hatem / Karimi, Mohammad Mahdi / Stoll, Isabelle / Ugrinova, Iva / Schröder, Maria / Fontaine-Pelletier, Emeline / Omran, Ziad / Bronner, Christian / Dimitrov, Stefan / Hamiche, Ali

    Journal of molecular biology

    2020  Volume 433, Issue 6, Page(s) 166659

    Abstract: Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we ... ...

    Abstract Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach. Our data reveal a clear correlation between CpG density, promoter activity and accumulation of active or repressive histone marks. CGI boundaries define the chromatin promoter regions that will be epigenetically modified. CpG-rich promoters are targeted by histone modifications and histone variants, while CpG-poor promoters are regulated by DNA methylation. CGIs boundaries, but not transcriptional activity, are essential determinants of H2A.Z positioning in vicinity of the promoters, suggesting that the presence of H2A.Z is not related to transcriptional control. Accordingly, H2A.Z depletion has no impact on gene expression of arrested mouse embryonic fibroblasts. Therefore, the underlying DNA sequence, the promoter CpG density and, to a lesser extent, transcriptional activity, are key factors implicated in promoter chromatin architecture.
    MeSH term(s) Animals ; Chromatin/metabolism ; Chromatin/ultrastructure ; Chromatin Assembly and Disassembly ; Computational Biology/methods ; CpG Islands ; DNA Methylation ; Embryo, Mammalian ; Epigenesis, Genetic ; Epigenome ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Histones/chemistry ; Histones/deficiency ; Histones/genetics ; Histones/metabolism ; Mice ; Mice, Knockout ; Primary Cell Culture ; Promoter Regions, Genetic ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Protein Processing, Post-Translational
    Chemical Substances Chromatin ; H2az1 protein, mouse ; Histones ; Protein Isoforms
    Language English
    Publishing date 2020-10-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2020.09.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: CpG Islands Shape the Epigenome Landscape

    Papin, Christophe / Le Gras, Stéphanie / Ibrahim, Abdulkhaleg / Salem, Hatem / Karimi, Mohammad Mahdi / Stoll, Isabelle / Ugrinova, Iva / Schröder, Maria / Fontaine-Pelletier, Emeline / Omran, Ziad / Bronner, Christian / Dimitrov, Stefan / Hamiche, Ali

    Journal of molecular biology. 2020 Sept. 22,

    2020  

    Abstract: Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we ... ...

    Abstract Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach. Our data reveal a clear correlation between CpG density, promoter activity and accumulation of active or repressive histone marks. CGI boundaries define the chromatin promoter regions that will be epigenetically modified. CpG-rich promoters are targeted by histone modifications and histone variants, while CpG-poor promoters are regulated by DNA methylation. CGIs boundaries, but not transcriptional activity, are essential determinants of H2A.Z positioning in vicinity of the promoters, suggesting that the presence of H2A.Z is not related to transcriptional control. Accordingly, H2A.Z depletion has no impact on gene expression of arrested mouse embryonic fibroblasts. Therefore, the underlying DNA sequence, the promoter CpG density and, to a lesser extent, transcriptional activity, are key factors implicated in promoter chromatin architecture.
    Keywords DNA ; DNA methylation ; bioinformatics ; epigenetics ; epigenome ; fibroblasts ; gene expression ; genomic islands ; histone code ; histones ; landscapes ; mice ; nucleosomes ; promoter regions ; transcription (genetics)
    Language English
    Dates of publication 2020-0922
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2020.09.018
    Database NAL-Catalogue (AGRICOLA)

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