Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues
Objective We conducted a comprehensive gene expression meta‐analysis in dermatomyositis (DM) muscle and skin tissues to identify shared disease‐relevant genes and pathways across tissues. Methods Six publicly available data sets from DM muscle and two from skin were identified. Meta‐analysis was per...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11081 |
| _version_ | 1818084729728008192 |
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| author | Jessica Neely Dmitry Rychkov Manish Paranjpe Michael Waterfield Susan Kim Marina Sirota |
| author_facet | Jessica Neely Dmitry Rychkov Manish Paranjpe Michael Waterfield Susan Kim Marina Sirota |
| author_sort | Jessica Neely |
| collection | DOAJ |
| description | Objective We conducted a comprehensive gene expression meta‐analysis in dermatomyositis (DM) muscle and skin tissues to identify shared disease‐relevant genes and pathways across tissues. Methods Six publicly available data sets from DM muscle and two from skin were identified. Meta‐analysis was performed by first processing data sets individually then cross‐study normalization and merging creating tissue‐specific gene expression matrices for subsequent analysis. Complementary single‐gene and network analyses using Significance Analysis of Microarrays (SAM) and Weighted Gene Co‐expression Network Analysis (WGCNA) were conducted to identify genes significantly associated with DM. Cell‐type enrichment was performed using xCell. Results There were 544 differentially expressed genes (FC ≥ 1.3, q < 0.05) in muscle and 300 in skin. There were 94 shared upregulated genes across tissues enriched in type I and II interferon (IFN) signaling and major histocompatibility complex (MHC) class I antigen‐processing pathways. In a network analysis, we identified eight significant gene modules in muscle and seven in skin. The most highly correlated modules were enriched in pathways consistent with the single‐gene analysis. Additional pathways uncovered by WGCNA included T‐cell activation and T‐cell receptor signaling. In the cell‐type enrichment analysis, both tissues were highly enriched in activated dendritic cells and M1 macrophages. Conclusion There is striking similarity in gene expression across DM target tissues with enrichment of type I and II IFN pathways, MHC class I antigen‐processing, T‐cell activation, and antigen‐presenting cells. These results suggest IFN‐γ may contribute to the global IFN signature in DM, and altered auto‐antigen presentation through the class I MHC pathway may be important in disease pathogenesis. |
| first_indexed | 2024-12-10T19:58:31Z |
| format | Article |
| id | doaj.art-12a53910dfd64ec8b47e0b5bf232879d |
| institution | Directory Open Access Journal |
| issn | 2578-5745 |
| language | English |
| last_indexed | 2024-12-10T19:58:31Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj.art-12a53910dfd64ec8b47e0b5bf232879d2022-12-22T01:35:35ZengWileyACR Open Rheumatology2578-57452019-12-0111065766610.1002/acr2.11081Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target TissuesJessica Neely0Dmitry Rychkov1Manish Paranjpe2Michael Waterfield3Susan Kim4Marina Sirota5Department of Pediatrics University of California San FranciscoDepartment of Pediatrics University of California San FranciscoDepartment of Pediatrics University of California San FranciscoDepartment of Pediatrics University of California San FranciscoDepartment of Pediatrics University of California San FranciscoDepartment of Pediatrics University of California San FranciscoObjective We conducted a comprehensive gene expression meta‐analysis in dermatomyositis (DM) muscle and skin tissues to identify shared disease‐relevant genes and pathways across tissues. Methods Six publicly available data sets from DM muscle and two from skin were identified. Meta‐analysis was performed by first processing data sets individually then cross‐study normalization and merging creating tissue‐specific gene expression matrices for subsequent analysis. Complementary single‐gene and network analyses using Significance Analysis of Microarrays (SAM) and Weighted Gene Co‐expression Network Analysis (WGCNA) were conducted to identify genes significantly associated with DM. Cell‐type enrichment was performed using xCell. Results There were 544 differentially expressed genes (FC ≥ 1.3, q < 0.05) in muscle and 300 in skin. There were 94 shared upregulated genes across tissues enriched in type I and II interferon (IFN) signaling and major histocompatibility complex (MHC) class I antigen‐processing pathways. In a network analysis, we identified eight significant gene modules in muscle and seven in skin. The most highly correlated modules were enriched in pathways consistent with the single‐gene analysis. Additional pathways uncovered by WGCNA included T‐cell activation and T‐cell receptor signaling. In the cell‐type enrichment analysis, both tissues were highly enriched in activated dendritic cells and M1 macrophages. Conclusion There is striking similarity in gene expression across DM target tissues with enrichment of type I and II IFN pathways, MHC class I antigen‐processing, T‐cell activation, and antigen‐presenting cells. These results suggest IFN‐γ may contribute to the global IFN signature in DM, and altered auto‐antigen presentation through the class I MHC pathway may be important in disease pathogenesis.https://doi.org/10.1002/acr2.11081 |
| spellingShingle | Jessica Neely Dmitry Rychkov Manish Paranjpe Michael Waterfield Susan Kim Marina Sirota Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues ACR Open Rheumatology |
| title | Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues |
| title_full | Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues |
| title_fullStr | Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues |
| title_full_unstemmed | Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues |
| title_short | Gene Expression Meta‐Analysis Reveals Concordance in Gene Activation, Pathway, and Cell‐Type Enrichment in Dermatomyositis Target Tissues |
| title_sort | gene expression meta analysis reveals concordance in gene activation pathway and cell type enrichment in dermatomyositis target tissues |
| url | https://doi.org/10.1002/acr2.11081 |
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