Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples
Abstract Background Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mec...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | BMC Medical Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12920-019-0567-7 |
| _version_ | 1818740796845719552 |
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| author | Zandra C. Félix Garza Michael Lenz Joerg Liebmann Gökhan Ertaylan Matthias Born Ilja C. W. Arts Peter A. J. Hilbers Natal A. W. van Riel |
| author_facet | Zandra C. Félix Garza Michael Lenz Joerg Liebmann Gökhan Ertaylan Matthias Born Ilja C. W. Arts Peter A. J. Hilbers Natal A. W. van Riel |
| author_sort | Zandra C. Félix Garza |
| collection | DOAJ |
| description | Abstract Background Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mechanisms are much less understood. Recently, deconvolution methodologies have allowed the digital quantification of cell types in bulk tissue based on mRNA expression data from biopsies. Using these methods to study the cellular composition of the skin enables the rapid enumeration of multiple cell types, providing insight into the numerical changes of cell types associated with chronic inflammatory skin conditions. Here, we use deconvolution to enumerate the cellular composition of the skin and estimate changes related to onset, progress, and treatment of these skin diseases. Methods A novel signature matrix, i.e. DerM22, containing expression data from 22 reference cell types, is used, in combination with the CIBERSORT algorithm, to identify and quantify the cellular subsets within whole skin biopsy samples. We apply the approach to public microarray mRNA expression data from the skin layers and 648 samples from healthy subjects and patients with psoriasis or atopic dermatitis. The methodology is validated by comparison to experimental results from flow cytometry and immunohistochemistry studies, and the deconvolution of independent data from isolated cell types. Results We derived the relative abundance of cell types from healthy, lesional, and non-lesional skin and observed a marked increase in the abundance of keratinocytes and leukocytes in the lesions of both inflammatory dermatological conditions. The relative fraction of these cells varied from healthy to diseased skin and from non-lesional to lesional skin. We show that changes in the relative abundance of skin-related cell types can be used to distinguish between mild and severe cases of psoriasis and atopic dermatitis, and trace the effect of treatment. Conclusions Our analysis demonstrates the value of this new resource in interpreting skin-derived transcriptomics data by enabling the direct quantification of cell types in a skin sample and the characterization of pathological changes in tissue composition. |
| first_indexed | 2024-12-18T01:46:26Z |
| format | Article |
| id | doaj.art-8eda2a98a4ae48ff99f8df736bc516fb |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-18T01:46:26Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-8eda2a98a4ae48ff99f8df736bc516fb2022-12-21T21:25:10ZengBMCBMC Medical Genomics1755-87942019-08-0112111410.1186/s12920-019-0567-7Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samplesZandra C. Félix Garza0Michael Lenz1Joerg Liebmann2Gökhan Ertaylan3Matthias Born4Ilja C. W. Arts5Peter A. J. Hilbers6Natal A. W. van Riel7Department of Biomedical Engineering, Eindhoven University of TechnologyMaastricht Centre for Systems Biology (MaCSBio), Maastricht UniversityPhilips Electronics Netherlands B.V., ResearchMaastricht Centre for Systems Biology (MaCSBio), Maastricht UniversityPhilips Electronics Netherlands B.V., ResearchMaastricht Centre for Systems Biology (MaCSBio), Maastricht UniversityDepartment of Biomedical Engineering, Eindhoven University of TechnologyDepartment of Biomedical Engineering, Eindhoven University of TechnologyAbstract Background Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mechanisms are much less understood. Recently, deconvolution methodologies have allowed the digital quantification of cell types in bulk tissue based on mRNA expression data from biopsies. Using these methods to study the cellular composition of the skin enables the rapid enumeration of multiple cell types, providing insight into the numerical changes of cell types associated with chronic inflammatory skin conditions. Here, we use deconvolution to enumerate the cellular composition of the skin and estimate changes related to onset, progress, and treatment of these skin diseases. Methods A novel signature matrix, i.e. DerM22, containing expression data from 22 reference cell types, is used, in combination with the CIBERSORT algorithm, to identify and quantify the cellular subsets within whole skin biopsy samples. We apply the approach to public microarray mRNA expression data from the skin layers and 648 samples from healthy subjects and patients with psoriasis or atopic dermatitis. The methodology is validated by comparison to experimental results from flow cytometry and immunohistochemistry studies, and the deconvolution of independent data from isolated cell types. Results We derived the relative abundance of cell types from healthy, lesional, and non-lesional skin and observed a marked increase in the abundance of keratinocytes and leukocytes in the lesions of both inflammatory dermatological conditions. The relative fraction of these cells varied from healthy to diseased skin and from non-lesional to lesional skin. We show that changes in the relative abundance of skin-related cell types can be used to distinguish between mild and severe cases of psoriasis and atopic dermatitis, and trace the effect of treatment. Conclusions Our analysis demonstrates the value of this new resource in interpreting skin-derived transcriptomics data by enabling the direct quantification of cell types in a skin sample and the characterization of pathological changes in tissue composition.http://link.springer.com/article/10.1186/s12920-019-0567-7SkinEpidermisDermisChronic inflammatory skin diseasesLeukocytesMicroarrays |
| spellingShingle | Zandra C. Félix Garza Michael Lenz Joerg Liebmann Gökhan Ertaylan Matthias Born Ilja C. W. Arts Peter A. J. Hilbers Natal A. W. van Riel Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples BMC Medical Genomics Skin Epidermis Dermis Chronic inflammatory skin diseases Leukocytes Microarrays |
| title | Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| title_full | Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| title_fullStr | Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| title_full_unstemmed | Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| title_short | Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| title_sort | characterization of disease specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples |
| topic | Skin Epidermis Dermis Chronic inflammatory skin diseases Leukocytes Microarrays |
| url | http://link.springer.com/article/10.1186/s12920-019-0567-7 |
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