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Clinical Correlations of Transcriptional Profile in Patients Infected With Avian Influenza H7N9 Virus

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      Abstract

      This study correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection with clinical data of patients. Biologically significant transcriptomic profiles associated with blood oxygenation and viral load in the lower respiratory tract were defined.

      Abstract

      Background

      Avian influenza A (H7N9) viruses emerged in China in 2013 and caused zoonotic disease associated with a case-fatality ratio of over 30%. Transcriptional profiles in peripheral blood reflect host responses and can help to elucidate disease pathogenesis.

      Methods

      We correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection and determined the biological significances from the analysis.

      Results

      We found that specific gene expression profiles in the blood were strongly correlated with the Pao 2/Fio 2 ratio and viral load in the lower respiratory tract. Cell cycle and leukocyte-related immunity were activated at the acute stage of the infection while T-cell functions and various metabolic processes were associated with the recovery phase of the illness. A transition from systemic innate to adaptive immunity was found.

      Conclusions

      We developed a novel approach for transcriptomic analysis to identify key host responses that were strongly correlated with specific clinical and virologic parameters in patients with H7N9 infection.

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      Most cited references 38

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      High density oligonucleotide array technology is widely used in many areas of biomedical research for quantitative and highly parallel measurements of gene expression. Affymetrix GeneChip arrays are the most popular. In this technology each gene is typically represented by a set of 11-20 pairs of probes. In order to obtain expression measures it is necessary to summarize the probe level data. Using two extensive spike-in studies and a dilution study, we developed a set of tools for assessing the effectiveness of expression measures. We found that the performance of the current version of the default expression measure provided by Affymetrix Microarray Suite can be significantly improved by the use of probe level summaries derived from empirically motivated statistical models. In particular, improvements in the ability to detect differentially expressed genes are demonstrated.
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        Gene Ontology Consortium: going forward

        The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology.
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          Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.

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            Author and article information

            Affiliations
            [1 ]State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
            [2 ]Hong Kong University-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
            [3 ]Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences
            [4 ]Dongguan People’s Hospital, China
            [5 ]Department of Integrative Structural and Computational Biology
            [6 ]Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California
            [7 ]Institute for Cellular and Molecular Biology, University of Texas at Austin
            Author notes

            W. G., Z. Y. and N. C. W. contributed equally.

            Correspondence: C. K. P. Mok, PhD, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Guangzhou, Guangdong, China ( ch02mkp@ 123456hku.hk ).
            Journal
            J Infect Dis
            J. Infect. Dis
            jid
            The Journal of Infectious Diseases
            Oxford University Press (US )
            0022-1899
            1537-6613
            15 October 2018
            28 May 2018
            28 May 2018
            : 218
            : 8
            : 1238-1248
            29846612 6129114 10.1093/infdis/jiy317 jiy317
            © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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            Pages: 11
            Product
            Funding
            Funded by: National Natural Science Foundation of China 10.13039/501100001809
            Award ID: 81761128014
            Funded by: Science Research Project of the Guangdong Province
            Award ID: 2016A050503047
            Funded by: Municipal Science and Technology Bureau Foundation of Guangzhou
            Award ID: 2014Y2-00031
            Funded by: Research Grants Council of the Hong Kong Special Administrative Region, China
            Award ID: T11-705/14N
            Funded by: National Institutes of Health 10.13039/100000002
            Award ID: R56 AI127371
            Funded by: Croucher Foundation 10.13039/501100001692
            Categories
            Major Articles and Brief Reports
            Viruses

            Infectious disease & Microbiology

            o, transcriptomic, 2, io, 2/ f, pa, avian influenza, h7n9

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