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Academia molecular biology and genomics.
By Mingjie Li and Tirupapuliyur Damodaran.
Lupus nephritis (LN) is molecularly heterogeneous, and transcriptomic comparisons of histological classes can be confounded by renal tissue compartment and repeated sampling of the same patient.
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We reanalyzed GSE127797 to compare class IV with class V LN using 44 Affymetrix Human Transcriptome Array 2.0 profiles from 25 patients; 19 patients contributed paired glomerular and tubulointerstitial profiles. A limma model included tissue compartment and estimated within-patient correlation (consensus correlation, 0.356).
No individual feature was significant after Benjamini–Hochberg (BH) correction. Using an explicitly exploratory threshold of nominal p < 0.05 and |log2 fold change| ≥ 0.5, 39 candidate genes were identified (24 higher in class IV and 15 higher in class V). No class-by-tissue interaction survived false-discovery-rate correction, and all 39 candidates had concordant effect directions in both tissue compartments. Excluding five quality-control-flagged profiles retained the direction of all 39 candidates, with 32 remaining above the original exploratory threshold and an all-feature log-fold-change correlation of r = 0.893. The log-fold-change and moderated- t rankings, both derived from the same limma fit, showed high within-fit concordance but were not treated as independent replication. A correlation-adjusted mean rank gene set test using a pre-ranked statistic (CAMERA-PR) sensitivity analysis supported the direction of all 10 displayed Gene Ontology (GO) and all 10 displayed Kyoto Encyclopedia of Genes and Genomes (KEGG) terms; 9 displayed GO terms and all 10 displayed KEGG terms were BH-significant under CAMERA-PR. Class IV showed greater B-cell/immunoglobulin, complement and phagocytosis-related signals, whereas class V showed greater amino-acid and xenobiotic-metabolism signals. A Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)-derived protein association network contained 24 nodes and 51 associations at the primary threshold. C-C motif chemokine ligand 2 ( CCL2 ) ranked first by maximal clique centrality in the primary and broad networks and second in the strict network.
Thus, pathway-level contrasts were supported by an inter-gene-correlation-aware sensitivity analysis, whereas individual candidate genes and network hubs remain exploratory and require external validation.
Published in Academia molecular biology and genomics.. The abstract is shown as published and remains the work of its authors; read the full article at the source.
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