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Series GSE149050 Query DataSets for GSE149050
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
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.
Overall design Assessment of the transcriptomic profiles of different immune cells in SLE
Web link
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
Submission date Apr 21, 2020
Last update date May 03, 2021
Contact name Ferhat Ay
Organization name La Jolla Institute for Immunology
Street address 9420 Athena Circle
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (288)
GSM4489145 001_L0038_HC_T
GSM4489146 002_L0088fresh_HC_T
GSM4489147 003_L0140_HC_T
BioProject PRJNA627214
SRA SRP257773

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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
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Raw data are available in SRA
Processed data are available on Series record

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