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  1. Article ; Online: DataCurator.jl: efficient, portable and reproducible validation, curation and transformation of large heterogeneous datasets using human-readable recipes compiled into machine-verifiable templates.

    Cardoen, Ben / Ben Yedder, Hanene / Lee, Sieun / Nabi, Ivan Robert / Hamarneh, Ghassan

    Bioinformatics advances

    2023  Volume 3, Issue 1, Page(s) vbad068

    Abstract: Large-scale processing of heterogeneous datasets in interdisciplinary research often requires time-consuming manual data curation. Ambiguity in the data layout and preprocessing conventions can easily compromise reproducibility and scientific discovery, ... ...

    Abstract Large-scale processing of heterogeneous datasets in interdisciplinary research often requires time-consuming manual data curation. Ambiguity in the data layout and preprocessing conventions can easily compromise reproducibility and scientific discovery, and even when detected, it requires time and effort to be corrected by domain experts. Poor data curation can also interrupt processing jobs on large computing clusters, causing frustration and delays. We introduce
    Language English
    Publishing date 2023-06-01
    Publishing country England
    Document type Journal Article
    ISSN 2635-0041
    ISSN (online) 2635-0041
    DOI 10.1093/bioadv/vbad068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Multitask Deep Learning Reconstruction and Localization of Lesions in Limited Angle Diffuse Optical Tomography.

    Ben Yedder, Hanene / Cardoen, Ben / Shokoufi, Majid / Golnaraghi, Farid / Hamarneh, Ghassan

    IEEE transactions on medical imaging

    2022  Volume 41, Issue 3, Page(s) 515–530

    Abstract: Diffuse optical tomography (DOT) leverages near-infrared light propagation through tissue to assess its optical properties and identify abnormalities. DOT image reconstruction is an ill-posed problem due to the highly scattered photons in the medium and ... ...

    Abstract Diffuse optical tomography (DOT) leverages near-infrared light propagation through tissue to assess its optical properties and identify abnormalities. DOT image reconstruction is an ill-posed problem due to the highly scattered photons in the medium and the smaller number of measurements compared to the number of unknowns. Limited-angle DOT reduces probe complexity at the cost of increased reconstruction complexity. Reconstructions are thus commonly marred by artifacts and, as a result, it is difficult to obtain an accurate reconstruction of target objects, e.g., malignant lesions. Reconstruction does not always ensure good localization of small lesions. Furthermore, conventional optimization-based reconstruction methods are computationally expensive, rendering them too slow for real-time imaging applications. Our goal is to develop a fast and accurate image reconstruction method using deep learning, where multitask learning ensures accurate lesion localization in addition to improved reconstruction. We apply spatial-wise attention and a distance transform based loss function in a novel multitask learning formulation to improve localization and reconstruction compared to single-task optimized methods. Given the scarcity of real-world sensor-image pairs required for training supervised deep learning models, we leverage physics-based simulation to generate synthetic datasets and use a transfer learning module to align the sensor domain distribution between in silico and real-world data, while taking advantage of cross-domain learning. Applying our method, we find that we can reconstruct and localize lesions faithfully while allowing real-time reconstruction. We also demonstrate that the present algorithm can reconstruct multiple cancer lesions. The results demonstrate that multitask learning provides sharper and more accurate reconstruction.
    MeSH term(s) Algorithms ; Artifacts ; Deep Learning ; Image Processing, Computer-Assisted/methods ; Tomography, Optical/methods
    Language English
    Publishing date 2022-03-02
    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.2021.3117276
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS

    Alan, Parsa / Vandevoorde, Kurt R. / Joshi, Bharat / Cardoen, Ben / Gao, Guang / Mohammadzadeh, Yahya / Hamarneh, Ghassan / Nabi, Ivan R.

    Cell. Mol. Life Sci.. 2022 Nov., v. 79, no. 11 p.565-565

    2022  

    Abstract: Mitochondria are major sources of cytotoxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, that when uncontrolled contribute to cancer progression. Maintaining a finely tuned, healthy mitochondrial population is essential for ... ...

    Abstract Mitochondria are major sources of cytotoxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, that when uncontrolled contribute to cancer progression. Maintaining a finely tuned, healthy mitochondrial population is essential for cellular homeostasis and survival. Mitophagy, the selective elimination of mitochondria by autophagy, monitors and maintains mitochondrial health and integrity, eliminating damaged ROS-producing mitochondria. However, mechanisms underlying mitophagic control of mitochondrial homeostasis under basal conditions remain poorly understood. E3 ubiquitin ligase Gp78 is an endoplasmic reticulum membrane protein that induces mitochondrial fission and mitophagy of depolarized mitochondria. Here, we report that CRISPR/Cas9 knockout of Gp78 in HT-1080 fibrosarcoma cells increased mitochondrial volume, elevated ROS production and rendered cells resistant to carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitophagy. These effects were phenocopied by knockdown of the essential autophagy protein ATG5 in wild-type HT-1080 cells. Use of the mito-Keima mitophagy probe confirmed that Gp78 promoted both basal and damage-induced mitophagy. Application of a spot detection algorithm (SPECHT) to GFP-mRFP tandem fluorescent-tagged LC3 (tfLC3)-positive autophagosomes reported elevated autophagosomal maturation in wild-type HT-1080 cells relative to Gp78 knockout cells, predominantly in proximity to mitochondria. Mitophagy inhibition by either Gp78 knockout or ATG5 knockdown reduced mitochondrial potential and increased mitochondrial ROS. Live cell analysis of tfLC3 in HT-1080 cells showed the preferential association of autophagosomes with mitochondria of reduced potential. Xenograft tumors of HT-1080 knockout cells show increased labeling for mitochondria and the cell proliferation marker Ki67 and reduced labeling for the TUNEL cell death reporter. Basal Gp78-dependent mitophagic flux is, therefore, selectively associated with reduced potential mitochondria promoting maintenance of a healthy mitochondrial population, limiting ROS production and tumor cell proliferation.
    Keywords CRISPR-Cas systems ; algorithms ; autophagosomes ; cell proliferation ; cyanides ; cytotoxicity ; endoplasmic reticulum ; fibrosarcoma ; homeostasis ; hydrazones ; hydrogen peroxide ; membrane proteins ; mitochondria ; mitophagy ; neoplasm cells ; neoplasm progression ; ubiquitin-protein ligase ; xenotransplantation
    Language English
    Dates of publication 2022-11
    Size p. 565.
    Publishing place Springer International Publishing
    Document type Article ; Online
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04585-8
    Database NAL-Catalogue (AGRICOLA)

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  4. Book ; Online: AI-based analysis of super-resolution microscopy

    Nabi, Ivan R. / Cardoen, Ben / Khater, Ismail M. / Gao, Guang / Wong, Timothy H. / Hamarneh, Ghassan

    Biological discovery in the absence of ground truth

    2023  

    Abstract: The nanoscale resolution of super-resolution microscopy has now enabled the use of fluorescent based molecular localization tools to study whole cell structural biology. Machine learning based analysis of super-resolution data offers tremendous potential ...

    Abstract The nanoscale resolution of super-resolution microscopy has now enabled the use of fluorescent based molecular localization tools to study whole cell structural biology. Machine learning based analysis of super-resolution data offers tremendous potential for discovery of new biology, that by definition is not known and lacks ground truth. Herein, we describe the application of weakly supervised learning paradigms to super-resolution microscopy and its potential to enable the accelerated exploration of the molecular architecture of subcellular macromolecules and organelles.

    Comment: 14 pages, 3 figures
    Keywords Quantitative Biology - Subcellular Processes ; Computer Science - Artificial Intelligence ; Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Machine Learning ; Physics - Biological Physics ; Quantitative Biology - Quantitative Methods
    Publishing date 2023-05-26
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS.

    Alan, Parsa / Vandevoorde, Kurt R / Joshi, Bharat / Cardoen, Ben / Gao, Guang / Mohammadzadeh, Yahya / Hamarneh, Ghassan / Nabi, Ivan R

    Cellular and molecular life sciences : CMLS

    2022  Volume 79, Issue 11, Page(s) 565

    Abstract: Mitochondria are major sources of cytotoxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, that when uncontrolled contribute to cancer progression. Maintaining a finely tuned, healthy mitochondrial population is essential for ... ...

    Abstract Mitochondria are major sources of cytotoxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, that when uncontrolled contribute to cancer progression. Maintaining a finely tuned, healthy mitochondrial population is essential for cellular homeostasis and survival. Mitophagy, the selective elimination of mitochondria by autophagy, monitors and maintains mitochondrial health and integrity, eliminating damaged ROS-producing mitochondria. However, mechanisms underlying mitophagic control of mitochondrial homeostasis under basal conditions remain poorly understood. E3 ubiquitin ligase Gp78 is an endoplasmic reticulum membrane protein that induces mitochondrial fission and mitophagy of depolarized mitochondria. Here, we report that CRISPR/Cas9 knockout of Gp78 in HT-1080 fibrosarcoma cells increased mitochondrial volume, elevated ROS production and rendered cells resistant to carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitophagy. These effects were phenocopied by knockdown of the essential autophagy protein ATG5 in wild-type HT-1080 cells. Use of the mito-Keima mitophagy probe confirmed that Gp78 promoted both basal and damage-induced mitophagy. Application of a spot detection algorithm (SPECHT) to GFP-mRFP tandem fluorescent-tagged LC3 (tfLC3)-positive autophagosomes reported elevated autophagosomal maturation in wild-type HT-1080 cells relative to Gp78 knockout cells, predominantly in proximity to mitochondria. Mitophagy inhibition by either Gp78 knockout or ATG5 knockdown reduced mitochondrial potential and increased mitochondrial ROS. Live cell analysis of tfLC3 in HT-1080 cells showed the preferential association of autophagosomes with mitochondria of reduced potential. Xenograft tumors of HT-1080 knockout cells show increased labeling for mitochondria and the cell proliferation marker Ki67 and reduced labeling for the TUNEL cell death reporter. Basal Gp78-dependent mitophagic flux is, therefore, selectively associated with reduced potential mitochondria promoting maintenance of a healthy mitochondrial population, limiting ROS production and tumor cell proliferation.
    MeSH term(s) Humans ; Mitophagy ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Reactive Oxygen Species/metabolism ; Ki-67 Antigen/metabolism ; Superoxides/metabolism ; Hydrogen Peroxide/pharmacology ; Mitochondria/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Autophagy/genetics
    Chemical Substances Carbonyl Cyanide m-Chlorophenyl Hydrazone (555-60-2) ; Reactive Oxygen Species ; Ki-67 Antigen ; Superoxides (11062-77-4) ; Hydrogen Peroxide (BBX060AN9V) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2022-10-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04585-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online: Deep Learning for Biomedical Image Reconstruction

    Yedder, Hanene Ben / Cardoen, Ben / Hamarneh, Ghassan

    A Survey

    2020  

    Abstract: Medical imaging is an invaluable resource in medicine as it enables to peer inside the human body and provides scientists and physicians with a wealth of information indispensable for understanding, modelling, diagnosis, and treatment of diseases. ... ...

    Abstract Medical imaging is an invaluable resource in medicine as it enables to peer inside the human body and provides scientists and physicians with a wealth of information indispensable for understanding, modelling, diagnosis, and treatment of diseases. Reconstruction algorithms entail transforming signals collected by acquisition hardware into interpretable images. Reconstruction is a challenging task given the ill-posed of the problem and the absence of exact analytic inverse transforms in practical cases. While the last decades witnessed impressive advancements in terms of new modalities, improved temporal and spatial resolution, reduced cost, and wider applicability, several improvements can still be envisioned such as reducing acquisition and reconstruction time to reduce patient's exposure to radiation and discomfort while increasing clinics throughput and reconstruction accuracy. Furthermore, the deployment of biomedical imaging in handheld devices with small power requires a fine balance between accuracy and latency.

    Comment: 26 pages, 8 figures
    Keywords Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Machine Learning
    Subject code 004
    Publishing date 2020-02-26
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Membrane contact site detection (MCS-DETECT) reveals dual control of rough mitochondria-ER contacts.

    Cardoen, Ben / Vandevoorde, Kurt R / Gao, Guang / Ortiz-Silva, Milene / Alan, Parsa / Liu, William / Tiliakou, Ellie / Vogl, A Wayne / Hamarneh, Ghassan / Nabi, Ivan R

    The Journal of cell biology

    2023  Volume 223, Issue 1

    Abstract: Identification and morphological analysis of mitochondria-ER contacts (MERCs) by fluorescent microscopy is limited by subpixel resolution interorganelle distances. Here, the membrane contact site (MCS) detection algorithm, MCS-DETECT, reconstructs ... ...

    Abstract Identification and morphological analysis of mitochondria-ER contacts (MERCs) by fluorescent microscopy is limited by subpixel resolution interorganelle distances. Here, the membrane contact site (MCS) detection algorithm, MCS-DETECT, reconstructs subpixel resolution MERCs from 3D super-resolution image volumes. MCS-DETECT shows that elongated ribosome-studded riboMERCs, present in HT-1080 but not COS-7 cells, are morphologically distinct from smaller smooth contacts and larger contacts induced by mitochondria-ER linker expression in COS-7 cells. RiboMERC formation is associated with increased mitochondrial potential, reduced in Gp78 knockout HT-1080 cells and induced by Gp78 ubiquitin ligase activity in COS-7 and HeLa cells. Knockdown of riboMERC tether RRBP1 eliminates riboMERCs in both wild-type and Gp78 knockout HT-1080 cells. By MCS-DETECT, Gp78-dependent riboMERCs present complex tubular shapes that intercalate between and contact multiple mitochondria. MCS-DETECT of 3D whole-cell super-resolution image volumes, therefore, identifies novel dual control of tubular riboMERCs, whose formation is dependent on RRBP1 and size modulated by Gp78 E3 ubiquitin ligase activity.
    MeSH term(s) Humans ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; COS Cells ; Animals ; Chlorocebus aethiops ; Ribosomes/metabolism
    Chemical Substances Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2023-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202206109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: ERGO: Efficient Recurrent Graph Optimized Emitter Density Estimation in Single Molecule Localization Microscopy.

    Cardoen, Ben / Yedder, Hanene Ben / Sharma, Anmol / Chou, Keng C / Nabi, Ivan Robert / Hamarneh, Ghassan

    IEEE transactions on medical imaging

    2019  Volume 39, Issue 6, Page(s) 1942–1956

    Abstract: Single molecule localization microscopy (SMLM) allows unprecedented insight into the three-dimensional organization of proteins at the nanometer scale. The combination of minimal invasive cell imaging with high resolution positions SMLM at the forefront ... ...

    Abstract Single molecule localization microscopy (SMLM) allows unprecedented insight into the three-dimensional organization of proteins at the nanometer scale. The combination of minimal invasive cell imaging with high resolution positions SMLM at the forefront of scientific discovery in cancer, infectious, and degenerative diseases. By stochastic temporal and spatial separation of light emissions from fluorescent labelled proteins, SMLM is capable of nanometer scale reconstruction of cellular structures. Precise localization of proteins in 3D astigmatic SMLM is dependent on parameter sensitive preprocessing steps to select regions of interest. With SMLM acquisition highly variable over time, it is non-trivial to find an optimal static parameter configuration. The high emitter density required for reconstruction of complex protein structures can compromise accuracy and introduce artifacts. To address these problems, we introduce two modular auto-tuning pre-processing methods: adaptive signal detection and learned recurrent signal density estimation that can leverage the information stored in the sequence of frames that compose the SMLM acquisition process. We show empirically that our contributions improve accuracy, precision and recall with respect to the state of the art. Both modules auto-tune their hyper-parameters to reduce the parameter space for practitioners, improve robustness and reproducibility, and are validated on a reference in silico dataset. Adaptive signal detection and density prediction can offer a practitioner, in addition to informed localization, a tool to tune acquisition parameters ensuring improved reconstruction of the underlying protein complex. We illustrate the challenges faced by practitioners in applying SMLM algorithms on real world data markedly different from the data used in development and show how ERGO can be run on new datasets without retraining while motivating the need for robust transfer learning in SMLM.
    MeSH term(s) Algorithms ; Artifacts ; Microscopy ; Reproducibility of Results ; Single Molecule Imaging
    Language English
    Publishing date 2019-12-25
    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.2019.2962361
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. 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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  10. 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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