Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures
In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can fu...
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sg-ntu-dr.10356-887552023-02-28T17:02:48Z Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures Tan, Kai Sen Yan, Yan Koh, Wai Ling Hiromi Li, Liang Choi, Hyungwon Tran, Thai Sugrue, Richard Wang, De Yun Chow, Vincent T. School of Biological Sciences Influenza Transcriptomics DRNTU::Science::Biological sciences In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can further bridge the gap in translating pre-clinical findings into clinical applications. We have previously generated a model of in vitro differentiated human nasal epithelial cells (hNECs) which elucidated the nasal-initiated repertoire of immune responses against respiratory viruses such as influenza A virus and rhinovirus. To assess their clinical utility, we performed a microarray analysis of influenza virus-infected hNECs to elucidate nasal epithelial-initiated responses. This was followed by a metagenomic analysis which revealed transcriptomic changes comparable with clinical influenza datasets. The primary target of influenza infection was observed to be the initiator of innate and adaptive immune genes, leaning toward type-1 inflammatory activation. In addition, the model also elucidated a down-regulation of metabolic processes specific to the nasal epithelium, and not present in other models. Furthermore, the hNEC model detected all 11 gene signatures unique to influenza infection identified from a previous study, thus supporting the utility of nasal-based diagnosis in clinical settings. In conclusion, this study highlights that hNECs can serve as a model for nasal-based clinical translational studies and diagnosis to unravel nasal epithelial responses to influenza in the population, and as a means to identify novel molecular diagnostic markers of severity. NMRC (Natl Medical Research Council, S’pore) Published version 2018-12-14T05:02:11Z 2019-12-06T17:10:18Z 2018-12-14T05:02:11Z 2019-12-06T17:10:18Z 2018 Journal Article Tan, K. S., Yan, Y., Koh, W. L. H., Li, L., Choi, H., Tran, T., Sugrue, R., et al. (2018). Comparative Transcriptomic and Metagenomic Analyses of Influenza Virus-Infected Nasal Epithelial Cells From Multiple Individuals Reveal Specific Nasal-Initiated Signatures. Frontiers in Microbiology, 9, 2685-. doi:10.3389/fmicb.2018.02685 https://hdl.handle.net/10356/88755 http://hdl.handle.net/10220/46976 10.3389/fmicb.2018.02685 en Frontiers in Microbiology © 2018 Tan, Yan, Koh, Li, Choi, Tran, Sugrue, Wang and Chow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 12 p. application/pdf |
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Influenza Transcriptomics DRNTU::Science::Biological sciences Tan, Kai Sen Yan, Yan Koh, Wai Ling Hiromi Li, Liang Choi, Hyungwon Tran, Thai Sugrue, Richard Wang, De Yun Chow, Vincent T. Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
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In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can further bridge the gap in translating pre-clinical findings into clinical applications. We have previously generated a model of in vitro differentiated human nasal epithelial cells (hNECs) which elucidated the nasal-initiated repertoire of immune responses against respiratory viruses such as influenza A virus and rhinovirus. To assess their clinical utility, we performed a microarray analysis of influenza virus-infected hNECs to elucidate nasal epithelial-initiated responses. This was followed by a metagenomic analysis which revealed transcriptomic changes comparable with clinical influenza datasets. The primary target of influenza infection was observed to be the initiator of innate and adaptive immune genes, leaning toward type-1 inflammatory activation. In addition, the model also elucidated a down-regulation of metabolic processes specific to the nasal epithelium, and not present in other models. Furthermore, the hNEC model detected all 11 gene signatures unique to influenza infection identified from a previous study, thus supporting the utility of nasal-based diagnosis in clinical settings. In conclusion, this study highlights that hNECs can serve as a model for nasal-based clinical translational studies and diagnosis to unravel nasal epithelial responses to influenza in the population, and as a means to identify novel molecular diagnostic markers of severity. |
author2 |
School of Biological Sciences |
author_facet |
School of Biological Sciences Tan, Kai Sen Yan, Yan Koh, Wai Ling Hiromi Li, Liang Choi, Hyungwon Tran, Thai Sugrue, Richard Wang, De Yun Chow, Vincent T. |
format |
Article |
author |
Tan, Kai Sen Yan, Yan Koh, Wai Ling Hiromi Li, Liang Choi, Hyungwon Tran, Thai Sugrue, Richard Wang, De Yun Chow, Vincent T. |
author_sort |
Tan, Kai Sen |
title |
Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
title_short |
Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
title_full |
Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
title_fullStr |
Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
title_full_unstemmed |
Comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
title_sort |
comparative transcriptomic and metagenomic analyses of influenza virus-infected nasal epithelial cells from multiple individuals reveal specific nasal-initiated signatures |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/88755 http://hdl.handle.net/10220/46976 |
_version_ |
1759855282660311040 |