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Phylogeographic and genetic network assessment of COVID-19 mitigation protocols on SARS-CoV-2 transmission in university campus residences

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eBioMedicine 2025年 116卷 105729-105729页

作者： Wertheim, Joel O. Vasylyeva, Tetyana I. Wood, Robert J. Cantrell, Kalen Contreras, Soraya Piña Feldheim, Aryeh Goyal, Ravi Havens, Jennifer L. Knight, Rob Laurent, Louise C. Moshiri, Niema Neuhard, Robert Sathe, Shashank Satterlund, Alysson Scioscia, Angela Song, Angela Y. Aigner, Stefan Andersen, Kristian G. Baer, Nathan A. Betty, Maryann Birmingham, Amanda Castro-Martinez, Anelizze Cheung, Willi De Hoff, Peter Fisch, Kathleen M. King, Alison J. Gangavarapu, Karthik Hakim, Abbas Henson, Benjamin Jepsen, Kristen Mac, Christina H. Ngo, Toan T. Nguyen, Kelly N. Ostrander, Tyler R. Perkins, Sarah Plascencia, Ashley Rivera, Andrea Rivera, Ariana Salido, Rodolfo A. Saucedo, Kieran C. Schwab, Madison Steedman, Allison L. Veder, Anthony Weiss, Alana Yeo, Gene W. Zeller, Mark Schooley, Robert T. Anderson, Cheryl M. Martin, Natasha K. Department of Medicine University of California San Diego La Jolla CA United States Department of Population Health and Disease Prevention University of California Irvine Irvine CA United States Herbert Wertheim School of Public Health and Human Longevity Science University of California San Diego La Jolla CA United States Department of Computer Science & Engineering University of California San Diego La Jolla CA United States Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA United States Department of Pediatrics University of California San Diego La Jolla CA United States Department of Bioengineering University of California San Diego La Jolla CA United States Department of Computer Science and Engineering University of California San Diego La Jolla CA United States Center for Microbiome Innovation University of California San Diego La Jolla CA United States Halıcıoğlu Data Science Institute University of California San Diego La Jolla CA United States Department of Obstetrics Gynecology and Reproductive Sciences University of California San Diego La Jolla CA United States Sanford Consortium of Regenerative Medicine University of California San Diego La Jolla CA United States University of California San Diego La Jolla CA United States

Background: Congregate living provides an ideal setting for SARS-CoV-2 transmission in which many outbreaks and superspreading events occurred. To avoid large outbreaks, universities turned to remote operations during the initial COVID-19 pandemic waves in 2020 and 2021. In late-2021, the University of California San Diego (UC San Diego) facilitated the return of students to campus with comprehensive testing, vaccination, masking, wastewater surveillance, and isolation policies. Methods: We performed molecular epidemiological and phylogeographic analysis of 4418 SARS-CoV-2 genomes sampled from UC San Diego students during the Omicron waves between December 2021 and September 2022, representing 58% of students with confirmed SARS-CoV-2 infection. We overlaid these analyses across on-campus residential information to assess the spread and persistence of SARS-CoV-2 within university residences. Findings: Within campus residences, SARS-CoV-2 transmission was frequent among students residing in the same room or suite. However, a quarter of pairs of suitemates with concurrent infections had distantly related viruses, suggesting separate sources of infection during periods of high incidence in the surrounding community. Students with concurrent infections residing in the same building were not at substantial increased probability of being members of the same transmission cluster. Genetic network and phylogeographic inference indicated that only between 3.1 and 12.4% of infections among students could be associated with transmission within buildings outside of individual suites. The only super-spreading event we detected was related to a large event outside campus residences. Interpretation: We found little evidence for sustained SARS-CoV-2 transmission within individual buildings, aside from students who resided in the same suite. Even in the face of heightened community transmission during the 2021–2022 Omicron waves, congregate living did not result in a heightened risk

关键词： Mitigation Phylogeography SARS-CoV-2 Transmission cluster University

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Analyses of protein cores reveal fundamental differences between solution and crystal structures

arXiv

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arXiv 2019年

作者： Mei, Zhe Treado, John D. Grigas, Alex T. Levine, Zachary A. Regan, Lynne O'Hern, Corey S. Integrated Graduate Program in Physical & Engineering Biology Yale University New HavenCT06520 United States Department of Chemistry Yale University New HavenCT06520 United States Department of Mechanical Engineering & Materials Science Yale University New HavenCT06520 United States Graduate Program in Computational Biology & Bioinformatics Yale University New HavenCT06520 United States Department of Pathology Yale University New HavenCT06520 United States Department of Molecular Biophysics and Biochemistry Yale University New HavenCT06520 United States Institute of Quantitative Biology Biochemistry and Biotechnology Center for Synthetic and Systems Biology School of Biological Sciences University of Edinburgh Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

There have been several studies suggesting that protein structures solved by NMR spectroscopy and x-ray crystallography show significant differences. To understand the origin of these differences, we assembled a database of high-quality protein structures solved by both methods. We also find significant differences between NMR and crystal structures|in the root-mean-square deviations of the Cα atomic positions, identities of core amino acids, backbone and sidechain dihedral angles, and packing fraction of core residues. In contrast to prior studies, we identify the physical basis for these differences by modelling protein cores as jammed packings of amino-acid-shaped particles. We find that we can tune the jammed packing fraction by varying the degree of thermalization used to generate the packings. For an athermal protocol, we find that the average jammed packing fraction is identical to that observed in the cores of protein structures solved by x-ray crystallography. In contrast, highly thermalized packing-generation protocols yield jammed packing fractions that are even higher than those observed in NMR structures. These results indicate that thermalized systems can pack more densely than athermal systems, which suggests a physical basis for the structural differences between protein structures solved by NMR and x-ray crystallography. Copyright © 2019, The Authors. All rights reserved.

关键词： X ray crystallography

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Array-Based High-Throughput Screening UNIT 5C.3 in Mouse Embryonic Stem Cells with shRNAs

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Current Protocols in Stem Cell biology 2013年第SUPPL.26期1卷 5C.3.1-5C.3.19页

作者： Wang, Chia-Hui Ma, Nianhan Lin, Yu-Tsen Wu, Cheng-Chung Wu, Hong-Jin Yu, Ching-Chia Hsiao, Michael Lu, Frank Leigh Schuyler, Scott C. Lu, Jean Genomics Research Center Academia Sinica Taipei Taiwan Institute of Systems Biology and Bioinformatics National Central University Taoyuan Taiwan Graduate Institute of Life Sciences National Defense Medical Center Taipei Taiwan Department of Pediatrics National Taiwan University Hospital and National Taiwan University Medical College Taipei Taiwan Department of Biomedical Sciences College of Medicine Chang Gung University Taoyuan County Taiwan Genomics and System Biology Program College of Life Science National Taiwan University Taipei Taiwan National Core Facility Program for Biotechnology National RNAi Platform Taipei Taiwan

High-throughput short-hairpin RNA (shRNA) lentivirus screening is a powerful tool for identifying multiple functional regulators in embryonic stem cells (ESCs). shRNA libraries can efficiently down-regulate target genes persistently with high efficiency. The concurrent measurement of relative cell number by alamarBlue (AB) assay and undifferentiated ESC markers via an alkaline phosphatase (ALP) activity assay in the same cell culture well provides an efficient and economical way to pinpoint factors crucial for ESC pluripotency and/or expansion. Most of the renewal pathways affect ALP activity. Thus, multiple positive and negative regulators can be identified by this method. In addition, morphological changes and/or the expression levels of specific pluripotency or differentiation markers examined by immunofluorescence can be used as secondary screens for target-gene selection. In summary, we describe an efficient way to identify multiple regulators of ESC renewal using shRNAs. © 2013 by John Wiley & Sons, Inc.

关键词： Embryonic stem cells High-throughput screening RNA interference Short-hairpin RNA

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Using physical features of protein core packing to distinguish real proteins from decoys

arXiv

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arXiv 2020年

作者： Grigas, Alex T. Mei, Zhe Treado, John D. Levine, Zachary A. Regan, Lynne O'Hern, Corey S. Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06520 United States Department of Chemistry Yale University New HavenCT06520 United States Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Department of Pathology Yale University New HavenCT06520 United States Department of Molecular Biophysics and Biochemistry Yale University New HavenCT06520 United States Institute of Quantitative Biology Biochemistry and Biotechnology Centre for Synthetic and Systems Biology School of Biological Sciences University of Edinburgh Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

The ability to consistently distinguish real protein structures from computationally generated model decoys is not yet a solved problem. One route to distinguish real protein structures from decoys is to delineate the important physical features that specify a real protein. For example, it has long been appreciated that the hydrophobic cores of proteins contribute signifficantly to their stability. As a dataset of decoys to compare with real protein structures, we studied submissions to the bi-annual CASP competition (speciffically CASP11, 12, and 13), in which researchers attempt to predict the structure of a protein only knowing its amino acid sequence. Our analysis reveals that many of the submissions possess cores that do not recapitulate the features that define real proteins. In particular, the model structures appear more densely packed (because of energetically unfavorable atomic overlaps), contain too few residues in the core, and have improper distributions of hydrophobic residues throughout the structure. Based on these observations, we developed a deep learning method, which incorporates key physical features of protein cores, to predict how well a computational model recapitulates the real protein structure without knowledge of the structure of the target sequence. By identifying the important features of protein structure, our method is able to rank decoys from the CASP competitions equally well, if not better than, state-of-the-art methods that incorporate many additional features. Copyright © 2020, The Authors. All rights reserved.

关键词： Proteins

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Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy

Nature Cancer

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Nature Cancer 2024年第3期5卷 400-419页

作者： Huang, Yu-Kai Cheng, Wei-Chung Kuo, Ting-Ting Yang, Juan-Cheng Wu, Yang-Chang Wu, Heng-Hsiung Lo, Chia-Chien Hsieh, Chih-Ying Wong, Sze-Ching Lu, Chih-Hao Wu, Wan-Ling Liu, Shih-Jen Li, Yi-Chuan Lin, Ching-Chan Shen, Chia-Ning Hung, Mien-Chie Lin, Jaw-Town Yeh, Chun-Chieh Sher, Yuh-Pyng Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cancer Biology and Precision Therapeutics Center China Medical University Taichung Taiwan Ph.D. Program for Cancer Biology and Drug Discovery China Medical University and Academia Sinica Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology College of Medical and Health Science Asia University Taichung Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology China Medical University Taichung Taiwan Division of Hematology and Oncology China Medical University Hospital Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine E-Da Hospital Kaohsiung Taiwan Department of Medicine School of Medicine China Medical University Taichung Taiwan Department of Surgery Organ Transplantation Center China Medical University Hospital Taichung Taiwan Institute of Biochemistry and Molecular Biology China Medical University Taichung Taiwan

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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Lineage relationship of CD8^＋ T cell subsets is revealed by progressive changes in the epigenetic landscape

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Cellular & Molecular Immunology 2016年第4期13卷 502-513页

作者： Joseph G. Crompton Manikandan Narayanan Suresh Cuddapah Rahul Roychoudhuri Yun Ji Wenjing Yang Shashank J. Patel Madhusudhanan Sukumar Douglas C. Palmer Weiqun Peng Ena Wang Francesco M. Marincola Christopher A. Klebanoff Keji Zhao John S. Tsang Luca Gatt-inoni Nicholas P. Restifo Surgery Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA Cambridge Institute for Medical Research University of Cam bridge Cambridge CB20XY UK Systems Genomics and Bioinformatics Unit Laboratory of Systems Biology National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA Department of Environmental Medicine New York University School of Medicine Tuxedo NY 10987 USA Experimental Transplantation and Immunology Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA Department of Physics The George Washington University Washington DC 20052 USA Research Branch Sidra Medical and Research Centre Doha Qatar Infectious Disease and Immunogenetics Section Department of Transfusion Medicine Clinical Center National Institutes of Health Bethesda MD 20892 USA Clinical Investigator Development Program NCI/NIH Bethesda MD 20892 USA Systems Biology Center National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892 USA. Lombardi Comprehensive Cancer Center Georgetown University Washington. DC 20007. United States. Bethesda. MD 20892. USA.

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8＋ T cells. Using a ChlP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 （H3K4me3） and H3 lysine 27 （H3K27me3） trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8＋ T-cell subsets. Taken together, our results suggest that CD8＋ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.

关键词： T淋巴细胞干细胞基因表达记忆抗原 CD8 赖氨酸胰岛素组蛋白类

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Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition

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European Journal of Medicinal Chemistry 2024年 265卷 116042页

作者： Tseng, Yu-Wei Yang, Tsung-Jung Hsu, Yuan-Ling Liu, Jyung-Hurng Tseng, Yin-Chen Hsu, Tse-Wei Lu, Yueh Pan, Szu-Hua Cheng, Ting-Jen Rachel Fang, Jim-Min Department of Chemistry National Taiwan University Taipei 106 Taiwan Graduate Institute of Medical Genomics and Proteomics College of Medicine National Taiwan University Taipei 100 Taiwan Graduate Institute of Genomics and Bioinformatics College of Life Sciences National Chung Hsing University Taichung 40227 Taiwan The Genomics Research Center Academia Sinica Taipei 115 Taiwan Doctoral Degree Program of Translational Medicine National Taiwan University Taipei 100 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 100 Taiwan

Dual-targeting anticancer agents 4–29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine–hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine–hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine–hydroxamate compounds for cancer monotherapy. © 2023 Elsevier Masson SAS

关键词： Breast cancer Histidine deacetylase Hydroxamate Katanin Lung cancer Microtubule Purine-type conjugate

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The impact of breast radiotherapy on the tumor genome and immune ecosystem

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Cell Reports 2025年第5期44卷 115703页

作者： Aislyn Schalck Tuan Tran Jianzhuo Li Emi Sei Shanshan Bai Min Hu Jerome Lin Scott J. Bright Samuel Reddick Fei Yang Harsh Batra Alejandro Contreras Maria Gabriela Raso Michael C. Stauder Karen E. Hoffman Jay P. Reddy Kevin T. Nead Benjamin D. Smith Gabriel O. Sawakuchi Wendy A. Woodward Stephanie S. Watowich Jennifer K. Litton Isabelle Bedrosian Elizabeth A. Mittendorf Huong Le-Petross Nicholas E. Navin Simona F. Shaitelman Department of Systems Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Graduate School of Biological Sciences University of Texas Houston TX 770303 USA Department of Radiation Physics University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Breast Radiation Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Vanderbilt University School of Medicine Nashville TN 37232 USA Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Janssen China Research & Development Johnson&Johnson Shanghai 201210 China Department of Anatomical Pathology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Immunology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Breast Medical Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Breast Surgical Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Division of Breast Surgery Department of Surgery Brigham and Women’s Hospital Boston MA 02115 USA Breast Oncology Program Dana-Farber Brigham Cancer Center Boston MA 02115 USA Harvard Medical School Boston MA 02115 USA Department of Breast Imaging University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Bioinformatics and Computational Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. In tumor cells, the scDNA-seq data showed a high genomic selection of subclones in half of the patients with high ER expression, while the remaining number had low genomic selection and an interferon response. Collectively, these data provide insight into the impact of radiotherapy in ER+ breast cancer patients.

关键词： single cell genomics breast cancer radiation tumor microenvironment

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Evolutionary Pressure against MHC Class II Binding Cancer Mutations (vol 175, pg 416, 2018)

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CELL 2018年第7期175卷 1991-1991页

作者： Pyke, Rachel Marty Thompson, Wesley Kurt Salem, Rany M. Font-Burgada, Joan Zanetti, Maurizio Carter, Hannah Department of Medicine Division of Medical Genetics University of California San Diego La Jolla CA 92093 USA Bioinformatics and Systems Biology Program University of California San Diego La Jolla CA 92093 USA Department of Family Medicine and Public Health Division of Biostatistics & Bioinformatics University of California San Diego La Jolla CA 92093 USA Department of Family Medicine and Public Health University of California San Diego La Jolla CA 92093 USA Moores Cancer Center University of California San Diego La Jolla CA 92093 USA The Laboratory of Immunology and Department of Medicine University of California San Diego La Jolla CA 92093 USA CIFAR MaRS Centre West Tower 661 University Ave. Suite 505 Toronto ON Canada

Summary The anti-cancer immune response against mutated peptides of potential immunological relevance (neoantigens) is primarily attributed to MHC-I-restricted cytotoxic CD8⁺ T cell responses. MHC-II-restricted CD4⁺ T cells also drive anti-tumor responses, but their relation to neoantigen selection and tumor evolution has not been systematically studied. Modeling the potential of an individual’s MHC-II genotype to present 1,018 driver mutations in 5,942 tumors, we demonstrate that the MHC-II genotype constrains the mutational landscape during tumorigenesis in a manner complementary to MHC-I. Mutations poorly bound to MHC-II are positively selected during tumorigenesis, even more than mutations poorly bound to MHC-I. This emphasizes the importance of CD4⁺ T cells in anti-tumor immunity. In addition, we observed less inter-patient variation in mutation presentation for MHC-II than for MHC-I. These differences were reflected by age at diagnosis, which was correlated with presentation by MHC-I only. Collectively, our results emphasize the central role of MHC-II presentation in tumor evolution.

关键词： MHC-II immunity cancer T cells immune editing driver mutations tumor evolution immunotherapy

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Dental Disease Detection based on CNN for Panoramic Dental Radiographs

Dental Disease Detection based on CNN for Panoramic Dental R...

引用

IEEE International Conference on Intelligent Computing and Information systems (ICICIS)

作者： Manar El Bagoury Mirna Al-Shetairy Omar Ahmed Samah S Mehanny Tassneem Hamdy Gihan Omar Marwan Akram Rana Mohamed Hebatullah Amr Walaa Gad Bioinformatics Program Faculty of Computer and Information Sciences Ain Shams University Cairo Egypt Computer Science Department Faculty of Computer and Information Sciences Ain Shams University Cairo Egypt Oral Biology Department Faculty of Dentistry Cairo and Galala Universities Cairo Egypt Oral and Maxillofacial Radiology Department Faculty of Dentistry Cairo University Cairo Egypt Oral Radiology Department Faculty of Oral and Dental Medicine Future University in Egypt Cairo Egypt Information Systems Department Faculty of Computer and Information Sciences Ain Shams University Cairo Egypt

Panoramic dental radiography is one of the examination tools frequently performed in dental clinics and hospitals as it captures a wide range of the dental region and its surroundings, but due to the complex structure of the dental area and lack of time, dentists focus on tiny parts of the images. With the help of Machine Learning, dentists can detect dental defects and anomalies faster and more accurately. In this study, a data set of 733 panoramic radiographs of adult patients was collected from the faculty of Oral and Dental Medicine, Future University, Egypt. Using a combination of pre-trained CNN architecture and a finetuned network, the collected panoramic radiographs were used to determine the optimal architecture. The purpose of this research was to develop a computer-aided detection system based on a finetuned CNN algorithm, and to evaluate the accuracy and usefulness of this system for the detection of proximal and occlusal caries, interdental and inter radicular alveolar bone loss, periapical lesions, and impacted teeth in panoramic radiographs. Different object detection models were tested to detect selected dental diseases that were found in the panoramic radiographs, and after a few experiments, the YOLOv5 architecture was proved to be the most optimal after achieving 0.61 mAP@0.5 and 0.28 mAP@ [0.5-0.95] for the total six classes. This is the best-achieved results to our knowledge.

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