Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis
Abstract 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 i...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
|
| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.976 |
| _version_ | 1797944078453702656 |
|---|---|
| author | Jingwen Deng Emmerik Leijten Michel Olde Nordkamp Guangjuan Zheng Juliëtte Pouw Weiyang Tao Sarita Hartgring Deepak Balak Rianne Rijken Runyue Huang Timothy Radstake Chuanjian Lu Aridaman Pandit |
| author_facet | Jingwen Deng Emmerik Leijten Michel Olde Nordkamp Guangjuan Zheng Juliëtte Pouw Weiyang Tao Sarita Hartgring Deepak Balak Rianne Rijken Runyue Huang Timothy Radstake Chuanjian Lu Aridaman Pandit |
| author_sort | Jingwen Deng |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T20:33:57Z |
| format | Article |
| id | doaj.art-753ad63c033b4965947ca085ba60f963 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-10T20:33:57Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-753ad63c033b4965947ca085ba60f9632023-01-25T04:06:34ZengWileyClinical and Translational Medicine2001-13262022-12-011212n/an/a10.1002/ctm2.976Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasisJingwen Deng0Emmerik Leijten1Michel Olde Nordkamp2Guangjuan Zheng3Juliëtte Pouw4Weiyang Tao5Sarita Hartgring6Deepak Balak7Rianne Rijken8Runyue Huang9Timothy Radstake10Chuanjian Lu11Aridaman Pandit12Guangdong Provincial Hospital of Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsGuangdong Provincial Hospital of Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaDepartment of Rheumatology and Clinical Immunology University Medical Center Utrecht, Utrecht University Utrecht The NetherlandsCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsDepartment of Dermatology LangeLand Hospital Zoetermeer The NetherlandsDepartment of Rheumatology and Clinical Immunology University Medical Center Utrecht, Utrecht University Utrecht The NetherlandsGuangdong Provincial Hospital of Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsGuangdong Provincial Hospital of Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaCenter for Translational ImmunologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe NetherlandsAbstract 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.https://doi.org/10.1002/ctm2.976gene networkhyperkeratinizationmulti‐omicspsoriasis |
| spellingShingle | Jingwen Deng Emmerik Leijten Michel Olde Nordkamp Guangjuan Zheng Juliëtte Pouw Weiyang Tao Sarita Hartgring Deepak Balak Rianne Rijken Runyue Huang Timothy Radstake Chuanjian Lu Aridaman Pandit Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis Clinical and Translational Medicine gene network hyperkeratinization multi‐omics 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 | gene network hyperkeratinization multi‐omics psoriasis |
| url | https://doi.org/10.1002/ctm2.976 |
| work_keys_str_mv | AT jingwendeng multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT emmerikleijten multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT micheloldenordkamp multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT guangjuanzheng multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT juliettepouw multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT weiyangtao multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT saritahartgring multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT deepakbalak multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT riannerijken multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT runyuehuang multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT timothyradstake multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT chuanjianlu multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis AT aridamanpandit multiomicsintegrationrevealsacorenetworkinvolvedinhostdefenceandhyperkeratinizationinpsoriasis |