Integrated Bioinformatics Analysis Identifies ELAVL1 and APP as Candidate Crucial Genes for Crohn’s Disease

Abstract

Immune imbalance and barrier destruction of intestinal mucosa are the central pathogenic factors of Crohn’s disease (CD). In this study, three independent microarray studies of CD were integrated and 9912 differentially expressed genes (DEGs) were analysed by NetworkAnalyst to screen candidate crucial genes. NetworkAnalyst identified ELAV-like RNA binding protein 1 (ELAVL1) as the most crucial upregulated gene and amyloid-β precursor protein (APP) as the most crucial downregulated gene in peripheral blood of CD patients. By computing significance with hypergeometric test based on the KEGG pathway database, upregulated DEGs highlight the pathways of T cell receptor signaling and the differentiation of T helpers. Downregulated DEGs were found enriched in pathways in multiple cancers, MAPK signaling, Rap1 signaling, and PI3K-AKT signaling. Further taking all DEGs together, Gene Set Enrichment Analysis (GSEA) brought out the NOD-like receptor (NLR) signaling pathway which could be regulated by ELAVL1. xCell found decreased naïve and differentiated T cell proportions in the peripheral blood of CD patients suggesting T cell migration to the intestinal tissue and/or exhaustion. Further, ELAVL1 expression correlating with multiple T cell proportions suggests that ELAVL1 may regulate T cell activation. These findings illustrated that ELAVL1 and APP were candidate crucial genes in the peripheral blood of CD patients. ELAVL1 possibly acts as a key regulator of T cell activation via the NLR signaling pathway. APP might be a downstream effector of infliximab treatment connecting with MAPK signaling.

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

“…We applied an integrated bioinformatics analysis to explore key regulators using NetworkAnalyst, a web-based visual analytics platform for comprehensive profiling, meta-analysis and systems-level interpretation of gene expression data (Zhou et al, 2019 ). The utility of NetworkAnalyst for identifying differentially expressed genes (DEGs) and pathways has recently been demonstrated (Santiago and Potashkin, 2015 ; Li et al, 2020 ; Dai et al, 2022 ). For example, network analyses have identified HNF4A and PTBP1 as effective biomarkers for Parkinson's disease (Santiago and Potashkin, 2015 ) and ELAVL1 and APP as crucial candidate genes for Crohn's disease (Li et al, 2020 ).…”

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn’s Disease Rats Treated with Herb-Partitioned Moxibustion

“… 66 It is reported that intestinal fibrosis is alleviated by enhancing the phosphorylation of AMPK in CD, 67 and previous bioinformatics analysis also identified MAPK signaling and PI3K-Akt signaling as crucial signaling pathways for Crohn’s Disease. 52 Another bioinformatics analysis study showed that the levels of autophagy-related proteins in FoxO signaling pathway were higher, but the levels of proteins related to inflammation in the intestinal mucosa were reduced. 68 FoxO4 transcription is temporarily suppressed in TNBS treatment and IBD patients.…”

Mapping Transcriptome Data to Protein–Protein Interaction Networks of Inflammatory Bowel Diseases Reveals Disease-Specific Subnetworks

“…Topological analysis reveals that the APP was the hub gene with the highest number of interactions with the expressed genes in the datasets. In addition, a recent study reported that APP gene is an important DEG for CD disease (Li et al, 2020). These results suggest that some similar genetic factors may be effective in both Alzheimer's disease (AD), and CD as APP is a critical gene in FIGURE 3 | Mapping transcriptome data to UC-specific PPI network for the discovery of subnetworks with KeyPathwayMiner (KPM).…”