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Chunk #37 — Results — Pathway analyses of the differentially expressed genes downstream of the six skipped exons

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RNA alternative splicing impacts the risk for alcohol use disorder.
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GO enrichment analysis (Supplementary Table S5) showed that the ELOVL7 splicing event implicated 250 differentially expressed genes that significantly enriched immune response pathways (Fig. 3D), such as, the type I interferon (IFN) signaling pathway (FDR = 7.20 × 10−06). Gene Set Enrichment Analysis (GSEA) [39] of three pathway databases (GO, KEGG, and MSigDB Hallmark) showed consistent enrichment for these immune pathways (Supplementary Table S6) along with several neural pathways, including glial cell differentiation and neurogenesis regulation (Fig. 3E, F). Neuroimmune pathways were commonly enriched for multiple SE events, including TNF, NF- κB, IL6-JAK-STAT3, IL2-STAT5, NOD-like receptor (NLR) signaling pathways, as well as T cell activation and differentiation (Supplementary Table S6). Noteworthy, the complement cascade, which is part of the innate immune system involved in alcoholic liver disease [62], was enriched for the SE events in ELOVL7, LINC00665, NSUN4, and SRRM2. We also found that epithelial-mesenchymal transition (EMT) was enriched for the SE events in ELOVL7, SRRM2 and TBC1D5 and was depleted for DRC1 and LINC00665 in GSEA. Recent studies suggest that genes associated with EMT have altered expression levels in