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  1. Article ; Online: DEEMD: Drug Efficacy Estimation Against SARS-CoV-2 Based on Cell Morphology With Deep Multiple Instance Learning.

    Saberian, M Sadegh / Moriarty, Kathleen P / Olmstead, Andrea D / Hallgrimson, Christian / Jean, Francois / Nabi, Ivan R / Libbrecht, Maxwell W / Hamarneh, Ghassan

    IEEE transactions on medical imaging

    2022  Volume 41, Issue 11, Page(s) 3128–3145

    Abstract: Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular ... ...

    Abstract Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular pathways and induce reorganization of subcellular structures to support their life cycle. These morphological changes can be quantified using bioimaging techniques. In this work, we developed DEEMD: a computational pipeline using deep neural network models within a multiple instance learning framework, to identify putative treatments effective against SARS-CoV-2 based on morphological analysis of the publicly available RxRx19a dataset. This dataset consists of fluorescence microscopy images of SARS-CoV-2 non-infected cells and infected cells, with and without drug treatment. DEEMD first extracts discriminative morphological features to generate cell morphological profiles from the non-infected and infected cells. These morphological profiles are then used in a statistical model to estimate the applied treatment efficacy on infected cells based on similarities to non-infected cells. DEEMD is capable of localizing infected cells via weak supervision without any expensive pixel-level annotations. DEEMD identifies known SARS-CoV-2 inhibitors, such as Remdesivir and Aloxistatin, supporting the validity of our approach. DEEMD can be explored for use on other emerging viruses and datasets to rapidly identify candidate antiviral treatments in the future. Our implementation is available online at https://www.github.com/Sadegh-Saberian/DEEMD.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 622531-7
    ISSN 1558-254X ; 0278-0062
    ISSN (online) 1558-254X
    ISSN 0278-0062
    DOI 10.1109/TMI.2022.3178523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Super resolution microscopy and deep learning identify Zika virus reorganization of the endoplasmic reticulum.

    Long, Rory K M / Moriarty, Kathleen P / Cardoen, Ben / Gao, Guang / Vogl, A Wayne / Jean, François / Hamarneh, Ghassan / Nabi, Ivan R

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 20937

    Abstract: The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of ER membranes to facilitate viral replication. ... ...

    Abstract The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of ER membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to distinguish ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and allow for better understanding of how ER morphology changes due to viral infection.
    MeSH term(s) Brain/pathology ; Brain/virology ; Cell Line, Tumor ; Deep Learning ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/ultrastructure ; Extracellular Matrix/metabolism ; Humans ; Microscopy/methods ; Organoids/metabolism ; Organoids/ultrastructure ; Organoids/virology ; RNA, Double-Stranded/metabolism ; Viral Nonstructural Proteins/metabolism ; Zika Virus/physiology ; Zika Virus/ultrastructure ; Zika Virus Infection/virology
    Chemical Substances RNA, Double-Stranded ; Viral Nonstructural Proteins
    Language English
    Publishing date 2020-12-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-77170-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: DEEMD

    Saberian, M. Sadegh / Moriarty, Kathleen P. / Olmstead, Andrea D. / Hallgrimson, Christian / Jean, François / Nabi, Ivan R. / Libbrecht, Maxwell W. / Hamarneh, Ghassan

    Drug Efficacy Estimation against SARS-CoV-2 based on cell Morphology with Deep multiple instance learning

    2021  

    Abstract: Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular ... ...

    Abstract Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular pathways and induce reorganization of subcellular structures to support their life cycle. These morphological changes can be quantified using bioimaging techniques. In this work, we developed DEEMD: a computational pipeline using deep neural network models within a multiple instance learning framework, to identify putative treatments effective against SARS-CoV-2 based on morphological analysis of the publicly available RxRx19a dataset. This dataset consists of fluorescence microscopy images of SARS-CoV-2 non-infected cells and infected cells, with and without drug treatment. DEEMD first extracts discriminative morphological features to generate cell morphological profiles from the non-infected and infected cells. These morphological profiles are then used in a statistical model to estimate the applied treatment efficacy on infected cells based on similarities to non-infected cells. DEEMD is capable of localizing infected cells via weak supervision without any expensive pixel-level annotations. DEEMD identifies known SARS-CoV-2 inhibitors, such as Remdesivir and Aloxistatin, supporting the validity of our approach. DEEMD can be explored for use on other emerging viruses and datasets to rapidly identify candidate antiviral treatments in the future}. Our implementation is available online at https://www.github.com/Sadegh-Saberian/DEEMD
    Keywords Computer Science - Machine Learning ; Computer Science - Computer Vision and Pattern Recognition ; Quantitative Biology - Quantitative Methods
    Subject code 004
    Publishing date 2021-05-10
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum

    Long, Rory K. M. / Moriarty, Kathleen P. / Cardoen, Ben / Gao, Guang / Vogl, A. Wayne / Jean, François / Hamarneh, Ghassan / Nabi, Ivan R.

    bioRxiv

    Abstract: The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to ... ...

    Abstract The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to identify ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and may be of use to screen for inhibitors of infection by ER-reorganizing viruses.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.05.12.091611
    Database COVID19

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