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Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis

OBJECTIVES: The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. METHODS: We collected the skin tissue biopsies and swabs in both...

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Autores principales: Deng, Jingwen, Leijten, Emmerik, Nordkamp, Michel Olde, Zheng, Guangjuan, Pouw, Juliëtte, Tao, Weiyang, Hartgring, Sarita, Balak, Deepak, Rijken, Rianne, Huang, Runyue, Radstake, Timothy, Lu, Chuanjian, Pandit, Aridaman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763538/
https://www.ncbi.nlm.nih.gov/pubmed/36536476
http://dx.doi.org/10.1002/ctm2.976
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author Deng, Jingwen
Leijten, Emmerik
Nordkamp, Michel Olde
Zheng, Guangjuan
Pouw, Juliëtte
Tao, Weiyang
Hartgring, Sarita
Balak, Deepak
Rijken, Rianne
Huang, Runyue
Radstake, Timothy
Lu, Chuanjian
Pandit, Aridaman
author_facet Deng, Jingwen
Leijten, Emmerik
Nordkamp, Michel Olde
Zheng, Guangjuan
Pouw, Juliëtte
Tao, Weiyang
Hartgring, Sarita
Balak, Deepak
Rijken, Rianne
Huang, Runyue
Radstake, Timothy
Lu, Chuanjian
Pandit, Aridaman
author_sort Deng, Jingwen
collection PubMed
description OBJECTIVES: The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. METHODS: We collected the skin tissue biopsies and swabs in both lesional and non‐lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high‐throughput RNA‐sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling. RESULTS: We found that lesional and non‐lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation. By using co‐expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a ‘core’ set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network. CONCLUSIONS: We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin.
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spelling pubmed-97635382022-12-20 Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis Deng, Jingwen Leijten, Emmerik Nordkamp, Michel Olde Zheng, Guangjuan Pouw, Juliëtte Tao, Weiyang Hartgring, Sarita Balak, Deepak Rijken, Rianne Huang, Runyue Radstake, Timothy Lu, Chuanjian Pandit, Aridaman Clin Transl Med Research Articles OBJECTIVES: The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. METHODS: We collected the skin tissue biopsies and swabs in both lesional and non‐lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high‐throughput RNA‐sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling. RESULTS: We found that lesional and non‐lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation. By using co‐expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a ‘core’ set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network. CONCLUSIONS: We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin. John Wiley and Sons Inc. 2022-12-19 /pmc/articles/PMC9763538/ /pubmed/36536476 http://dx.doi.org/10.1002/ctm2.976 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Deng, Jingwen
Leijten, Emmerik
Nordkamp, Michel Olde
Zheng, Guangjuan
Pouw, Juliëtte
Tao, Weiyang
Hartgring, Sarita
Balak, Deepak
Rijken, Rianne
Huang, Runyue
Radstake, Timothy
Lu, Chuanjian
Pandit, Aridaman
Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title_full Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title_fullStr Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title_full_unstemmed Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title_short Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
title_sort multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763538/
https://www.ncbi.nlm.nih.gov/pubmed/36536476
http://dx.doi.org/10.1002/ctm2.976
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