Multi-cell type gene coexpression network analysis reveals coordinated interferon response and cross-cell type
Bharat Panwar1, Benjamin J Schmiedel1, Shu Liang1
1La Jolla Institute for Immunology, La Jolla, California 92037, USA.
Genome Research
|March 6, 2021
Summary
Systemic lupus erythematosus (SLE) research identified distinct patient groups based on interferon response. This study reveals novel cross-cell type correlations and potential drug targets, including BAFF, for SLE treatment.
Area of Science:
- Immunology
- Genomics
- Computational Biology
Background:
- Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with no cure.
- Identifying cell-specific targets is challenging due to SLE's diverse clinical and cellular involvement.
- Understanding immune cell interactions is crucial for developing targeted SLE therapies.
Purpose of the Study:
- To identify cell-specific drug targets in SLE.
- To uncover cross-correlation relationships among immune cell expression programs.
- To stratify SLE patients based on interferon response signatures.
Main Methods:
- Analysis of six major circulating immune cell types from SLE patients.
- Differential gene expression and coexpression analysis.
- Development and application of a multi-cell type WGCNA (mWGCNA) framework.
Main Results:
- SLE patients stratified into IFN-negative (IFNneg) and IFN-positive (IFNpos) groups based on interferon response.
- Identified TNFSF13B/BAFF and IL1RN as potential monocyte-derived targets.
- mWGCNA revealed an interferon-stimulated gene (ISG) module across cell types and linked T helper cell markers to B cell response and myeloid TNFSF13B expression.
Conclusions:
- Hypothesis-free, data-driven analysis can discover novel drug targets for SLE.
- Cross-cell type correlations, particularly involving interferon response, are critical in SLE pathogenesis.
- Findings offer insights into SLE heterogeneity and potential therapeutic strategies for autoimmune diseases.
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