Lupus Nephritis Glomerular Signature

Which genes are most strongly dysregulated in glomerular lupus nephritis compared with control glomerular tissue?

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Key Findings

• Lupus nephritis glomeruli show strong upregulation of interferon-related and immune-response genes
• Prioritized genes include IFI44, IFI44L, MX1, TYROBP, C1QA, and MX2
• The molecular pattern is consistent with inflammatory and immune-mediated glomerular injury

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Clinical Context

Lupus nephritis is one of the most serious organ manifestations of systemic lupus erythematosus and a major cause of renal morbidity.

Although clinical classification remains essential, transcriptomic profiling can help identify molecular processes associated with glomerular injury and immune activation.

This project focuses specifically on the glomerular compartment, aiming to identify biologically coherent gene-expression signals linked to lupus nephritis.

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Dataset

• GEO accession: GSE32591

• Tissue compartment: glomerular biopsy samples

• Comparison: lupus nephritis vs control

• Final cohort used: 46 samples

  • 32 lupus nephritis
  • 14 controls

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Methods

R

• GEO data retrieval with GEOquery
• Differential expression analysis with limma

Python

• Post-processing and ranking of differentially expressed genes
• Volcano plot generation

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Workflow

1. Download and load GSE32591
2. Export phenotype and expression matrices
3. Filter glomerular samples only
4. Define lupus nephritis vs control groups
5. Run differential expression with limma
6. Rank genes by effect size and adjusted p-value
7. Generate volcano plot

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Main Outputs

• results/tables/ln_glomerular_limma_results.tsv
• results/tables/ln_glomerular_prioritized.tsv
• results/tables/ln_glomerular_top20.tsv
• results/figures/volcano_plot.png

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Biological Interpretation

Top-ranked genes included:

• IFI44
• IFI44L
• MX1
• TYROBP
• C1QA
• MX2

These genes are consistent with:

• interferon-driven immune activation
• inflammatory signaling
• innate immune cell involvement in glomerular injury

This pattern is clinically coherent with the known immunopathology of lupus nephritis.

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Interpretation

This analysis supports the idea that glomerular lupus nephritis is characterized by a strong immune and interferon-related molecular signature.

Rather than serving as a complex pipeline showcase, the project aims to provide a clear and reproducible example of transcriptomic analysis applied to a clinically meaningful nephrology question.

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Limitations

• Public dataset with fixed cohort composition
• Cross-sectional comparison
• No integration with longitudinal renal outcomes or treatment response
• Focus limited to one tissue compartment

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Why This Matters

This project demonstrates that:

• transcriptomic analysis can recover biologically meaningful signals in glomerular lupus nephritis
• immune-related signatures remain highly informative in renal tissue
• clinically oriented bioinformatics projects can be both reproducible and interpretable

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Reproducibility

Repository structure:

• data/
• docs/
• notebooks/
• python/
• r/
• results/figures/
• results/tables/

Key outputs include differential expression tables, prioritized gene lists, and the final volcano plot.

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Author

Cristian Arias, MD Specialist in Internal Medicine and Nephrology Healthcare Data Scientist / MSc Bioinformatics