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| Status |
Public on Feb 01, 2021 |
| Title |
Multi-cell type gene co-expression network analysis reveals coordinated interferon response and cross cell-type correlations in systemic lupus erythematosus |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women. A major obstacle in finding targeted therapies for SLE is its remarkable heterogeneity in clinical manifestations as well as in the involvement of distinct cell types. To identify cell-specific targets as well as cross-correlation relationships among expression programs of different cell types, we here analyze six major circulating immune cell types from SLE patient blood. Our results show that the presence of interferon response signature stratifies patients into two distinct groups (IFNneg vs IFNpos). Comparing these two groups using differential gene expression and differential gene co-expression analysis, we prioritize a relatively small list of genes from classical monocytes including two known immune modulators: TNFSF13B/BAFF (target of belimumab, an approved therapeutic for SLE) and IL1RN (the basis of anakinra, a therapeutic for rheumatoid arthritis). We then develop a multi-cell type extension of the weighted gene co-expression analysis (WGCNA) framework, termed mWGCNA. Applying mWGCNA to RNA-seq data from six sorted immune cell populations (15 SLE, 10 healthy donors), we identify a co-expression module with interferon-stimulated genes (ISGs) among all cell types and a cross-cell type correlation linking expression of specific T helper cell markers to B cell response as well as to TNFSF13B expression from myeloid cells, all of which in turn correlates with disease severity of IFNpos patients. Our results demonstrate the power of a hypothesis-free and data-driven approach to discover drug targets and to reveal novel cross-correlation across cell types in SLE with implications for other autoimmune diseases.
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| Overall design |
Assessment of the transcriptomic profiles of different immune cells in SLE
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| Web link |
https://ay-lab-tools.lji.org/sle/
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| Contributor(s) |
Panwar B, Schmiedel BJ, Liang S, White B, Rodriguez E, Kalunian K, McKnight AJ, Soloff R, Seumois G, Vijayanand P, Ay F |
| Citation(s) |
33674349 |
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| Submission date |
Apr 21, 2020 |
| Last update date |
May 03, 2021 |
| Contact name |
Ferhat Ay |
| E-mail(s) |
ferhatay@lji.org
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| Organization name |
La Jolla Institute for Immunology
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| Street address |
9420 Athena Circle
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (288)
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| Relations |
| BioProject |
PRJNA627214 |
| SRA |
SRP257773 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149050_Bulk_Human_RawCounts.txt.gz |
9.4 Mb |
(ftp)(http) |
TXT |
| GSE149050_Bulk_Human_TPM.txt.gz |
61.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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