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  1. Article: Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

    Jeong, Sohyun / Tsai, Ming-Ju / Shen, Changbing / Hsu, Yi-Hsiang

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: Musculoskeletal disorders were commonly reported in patients with multiple sclerosis. However, the underlying etiology linking Multiple Sclerosis (MS) and musculoskeletal disorders is not well studied. With large-scale Genome-Wide ... ...

    Abstract Background: Musculoskeletal disorders were commonly reported in patients with multiple sclerosis. However, the underlying etiology linking Multiple Sclerosis (MS) and musculoskeletal disorders is not well studied. With large-scale Genome-Wide Association Studies (GWAS) publicly available, we conducted genetic correlation analysis to identify shared pleiotropic genetic effects between MS and musculoskeletal traits. We also conducted Mendelian Randomization (MR) to estimate the causal relation between MS and increased risks of musculoskeletal disorders.
    Methods: Linkage Disequilibrium Score Regression (LDSR) analysis was performed to estimate heritability and genetic correlation. Univariable, multivariable, and bidirectional MR analyses were conducted to estimate the causal relation. These analyses were done by utilizing the recent GWAS summary statistics of MS, fracture, frailty, falls, and several musculoskeletal risk factors, including bone mineral density, lean mass, grip strengths, and vitamin D.
    Results: LDSR analysis showed a moderate genetic correlation of MS with falls (RG=0.10,
    Conclusion: Our study suggests a potential genetic correlation with shared pleiotropic genetic effects between MS and falls. However, we didn't find evidence to support the causal relation between MS and increased risks of falls, fracture, and frailty.
    Language English
    Publishing date 2023-09-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.12.23295444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: IConMHC: a deep learning convolutional neural network model to predict peptide and MHC-I binding affinity.

    Pei, Baikang / Hsu, Yi-Hsiang

    Immunogenetics

    2020  Volume 72, Issue 5, Page(s) 295–304

    Abstract: Tumor-specific neoantigens are mutated self-peptides presented by tumor cell major histocompatibility complex (MHC) molecules and are necessary to elicit host's anti-cancer cytotoxic T cell responses. It could be specifically recognized by neoantigen- ... ...

    Abstract Tumor-specific neoantigens are mutated self-peptides presented by tumor cell major histocompatibility complex (MHC) molecules and are necessary to elicit host's anti-cancer cytotoxic T cell responses. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs). However, current wet-lab assays for identifying peptide MHC binding are too expensive and time-consuming to meet the clinical needs. In this study, we developed an in silico method with a deep convolutional neural network (CNN) model, iConMHC, to predict peptide MHC binding affinity. Unlike other in silico methods that only learn from properties of amino acid in neoantigen peptides alone and/or MHCs alone, iConMHC learns from physical and chemical interaction properties between pairwise amino acids from the two molecules. These properties, such as contact potentials and distances in folded proteins, directly affect neoantigen-MHC binding affinity. In addition, IConMHC is a pan-allele model that is capable of making predictions for all the MHC alleles. Even for those rare MHC alleles without training data, iConMHC can make predictions with reasonable accuracy. We benchmarked iConMHC with other commonly used MHC-I binding predictors and found our model performs better than most of the pan-allele models.
    MeSH term(s) Alleles ; Amino Acid Sequence ; Antigens, Neoplasm/chemistry ; Antigens, Neoplasm/metabolism ; Computer Simulation ; Databases, Protein ; Deep Learning ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Humans ; Neural Networks, Computer ; Peptides/chemistry ; Peptides/metabolism ; Protein Binding ; Reproducibility of Results
    Chemical Substances Antigens, Neoplasm ; Histocompatibility Antigens Class I ; Peptides
    Language English
    Publishing date 2020-06-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 186560-2
    ISSN 1432-1211 ; 0093-7711
    ISSN (online) 1432-1211
    ISSN 0093-7711
    DOI 10.1007/s00251-020-01163-9
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  3. Article: Epidemiology, Clinical Features, and Unusual Complications of Norovirus Infection in Taiwan: What We Know after Rotavirus Vaccines.

    Lu, Meng-Che / Lin, Sheng-Chieh / Hsu, Yi-Hsiang / Chen, Shih-Yen

    Pathogens (Basel, Switzerland)

    2022  Volume 11, Issue 4

    Abstract: Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the ...

    Abstract Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the COVID-19 pandemic has been noted recently. Research in recent years has shown that different virus strains are associated with different clinical characteristics; moreover, there is a paucity of research into extraintestinal or unusual complications that may be associated with NoV. The genomic diversity of circulating NoVs is also complex and may vary significantly. Therefore, this short narrative review focuses on sharing the Taiwan experience of NoV infection including epidemiology, clinical features, and complications following suboptimal rotavirus immunization in Taiwan (after October 2006). We also highlight the unusual complications associated with NoV infections and the impacts of NoV infection during the COVID-19 pandemic in the literature for possible future research directions. To conclude, further research is needed to quantify the burden of NoV across the spectrum of disease severity in Taiwan. The evidence of the connection between NoV and the unusual complications is still lacking.
    Language English
    Publishing date 2022-04-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11040451
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  4. Article ; Online: The Human Virome: Viral Metagenomics, Relations with Human Diseases, and Therapeutic Applications.

    Bai, Geng-Hao / Lin, Sheng-Chieh / Hsu, Yi-Hsiang / Chen, Shih-Yen

    Viruses

    2022  Volume 14, Issue 2

    Abstract: The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, ...

    Abstract The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
    MeSH term(s) Animals ; COVID-19/therapy ; Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; Metagenomics/methods ; Mice ; Obesity/complications ; SARS-CoV-2/genetics ; Virome/genetics ; Virus Diseases/drug therapy ; Virus Diseases/therapy ; Viruses/classification ; Viruses/genetics
    Language English
    Publishing date 2022-01-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14020278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.

    Bai, Geng-Hao / Tsai, Meng-Chen / Lin, Sheng-Chieh / Hsu, Yi-Hsiang / Chen, Shih-Yen

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1212582

    Abstract: Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has ... ...

    Abstract Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has been extensively studied. While most past studies were conducted
    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1212582
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Corrigendum: Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.

    Bai, Geng-Hao / Tsai, Meng-Chen / Lin, Sheng-Chieh / Hsu, Yi-Hsiang / Chen, Shih-Yen

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1324539

    Abstract: This corrects the article DOI: 10.3389/fmicb.2023.1212582.]. ...

    Abstract [This corrects the article DOI: 10.3389/fmicb.2023.1212582.].
    Language English
    Publishing date 2023-12-01
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1324539
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  7. Article: The Human Virome: Viral Metagenomics, Relations with Human Diseases, and Therapeutic Applications

    Bai, Geng-Hao / Lin, Sheng-Chieh / Hsu, Yi-Hsiang / Chen, Shih-Yen

    Viruses. 2022 Jan. 28, v. 14, no. 2

    2022  

    Abstract: The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, ...

    Abstract The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
    Keywords COVID-19 infection ; digestive system ; human diseases ; humans ; metagenomics ; pandemic ; pathogenesis ; therapeutics
    Language English
    Dates of publication 2022-0128
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14020278
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Translating GWAS Findings to Inform Drug Repositioning Strategies for COVID-19 Treatment.

    Tsai, Ming-Ju / Jeong, Sohyun / Yu, Fangtang / Chen, Ting-Fu / Li, Peng-Hsuan / Juan, Hsueh-Fen / Huang, Jia-Hsin / Hsu, Yi-Hsiang

    Research square

    2023  

    Abstract: We developed a computational framework that integrates Genome-Wide Association Studies (GWAS) and post-GWAS analyses, designed to facilitate drug repurposing for COVID-19 treatment. The comprehensive approach combines transcriptomic-wide associations, ... ...

    Abstract We developed a computational framework that integrates Genome-Wide Association Studies (GWAS) and post-GWAS analyses, designed to facilitate drug repurposing for COVID-19 treatment. The comprehensive approach combines transcriptomic-wide associations, polygenic priority scoring, 3D genomics, viral-host protein-protein interactions, and small-molecule docking. Through GWAS, we identified nine druggable host genes associated with COVID-19 severity and SARS-CoV-2 infection, all of which show differential expression in COVID-19 patients. These genes include IFNAR1, IFNAR2, TYK2, IL10RB, CXCR6, CCR9, and OAS1. We performed an extensive molecular docking analysis of these targets using 553 small molecules derived from five therapeutically enriched categories, namely antibacterials, antivirals, antineoplastics, immunosuppressants, and anti-inflammatories. This analysis, which comprised over 20,000 individual docking analyses, enabled the identification of several promising drug candidates. All results are available via the DockCoV2 database (https://dockcov2.org/drugs/). The computational framework ultimately identified nine potential drug candidates: Peginterferon alfa-2b, Interferon alfa-2b, Interferon beta-1b, Ruxolitinib, Dactinomycin, Rolitetracycline, Irinotecan, Vinblastine, and Oritavancin. While its current focus is on COVID-19, our proposed computational framework can be applied more broadly to assist in drug repurposing efforts for a variety of diseases. Overall, this study underscores the potential of human genetic studies and the utility of a computational framework for drug repurposing in the context of COVID-19 treatment, providing a valuable resource for researchers in this field.
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3443080/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A transcriptomic and proteomic atlas of obesity and type 2 diabetes in cynomolgus monkeys.

    Zhang, Xianglong / Hu, Liangbiao George / Lei, Ying / Stolina, Marina / Homann, Oliver / Wang, Songli / Véniant, Murielle M / Hsu, Yi-Hsiang

    Cell reports

    2023  Volume 42, Issue 8, Page(s) 112952

    Abstract: Obesity and type 2 diabetes (T2D) remain major global healthcare challenges, and developing therapeutics necessitates using nonhuman primate models. Here, we present a transcriptomic and proteomic atlas of all the major organs of cynomolgus monkeys with ... ...

    Abstract Obesity and type 2 diabetes (T2D) remain major global healthcare challenges, and developing therapeutics necessitates using nonhuman primate models. Here, we present a transcriptomic and proteomic atlas of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues such as the liver and kidney. Immune-response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Moreover, we highlight some potential therapeutic targets, including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our study provides a resource for exploring the complex molecular mechanism of obesity and T2D and developing therapies for these diseases, with limitations including lack of hypothalamus, isolated islets of Langerhans, longitudinal data, and body fat percentage.
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/metabolism ; Macaca fascicularis ; Transcriptome/genetics ; Proteomics ; Obesity/genetics ; Obesity/metabolism
    Language English
    Publishing date 2023-08-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112952
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Molecular and Genetics-Based Systems for Tracing the Evolution and Exploring the Mechanisms of Human Norovirus Infections.

    Lin, Sheng-Chieh / Bai, Geng-Hao / Lin, Pei-Chun / Chen, Chung-Yung / Hsu, Yi-Hsiang / Lee, Yuan-Chang / Chen, Shih-Yen

    International journal of molecular sciences

    2023  Volume 24, Issue 10

    Abstract: Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. ... ...

    Abstract Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.
    MeSH term(s) Humans ; Norovirus/genetics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Caliciviridae Infections/genetics
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2023-05-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24109093
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