Chavez-Iglesias, E. | bioRxiv Science

bioRxiv2025

Consensus Co-Expression Analysis Identifies A Common Set Of Co-Expressed Genes Associated With Diabetic Peripheral Neuropathy And Chemotherapy-Induced Peripheral Neuropathy

BackgroundDiabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are major clinical challenges with limited therapeutic options. While these conditions arise from different causes, they may share common molecular mechanisms that could be targeted for intervention. MethodsWe performed consensus weighted gene co-expression network analysis (WGCNA) on two publicly available datasets: GSE185011 (DPN vs. healthy controls in peripheral blood mononuclear cells) and GSE173610 (paclitaxel-treated vs. control iPSC-derived sensory neurons). After filtering all but the most variable genes, consensus analysis was used to identify conserved co-expression modules across both conditions. ResultsConsensus analysis identified a 193-gene module (ME3/brown) significantly associated with both DPN (correlation=0.817, p=0.0040) and CIPN (correlation=0.971, p=0.0060). Functional enrichment analysis of this module revealed pathways related to Glycolysis, FoxO signaling, Apoptosis, and Autophagy. ConclusionsOur analysis reveals a convergent molecular signature underlying both DPN and CIPN, centered on metabolic reprogramming, transcriptional stress, and programmed cell death. These findings provide a systems-level framework for developing therapies targeting shared pathological mechanisms.

systems biology↗

bioRxiv2025

Alternative Splicing And Global Transcriptome Changes Associated With LPS Stimulation In Human Peripheral Blood Mononuclear Cells

IntroductionLipopolysaccharide (LPS), a major component of gram-negative bacterial cell walls, elicits strong innate immune activation and is a widely used model for studying inflammatory responses. While the transcriptional response to LPS stimulation has been characterized, the role of alternative splicing (AS) in modulating this response remains largely unexplored. MethodsUsing deep RNA sequencing of Peripheral Blood Mononuclear Cells from three healthy female donors, we evaluated transcriptome-wide differential gene expression and alternative splicing in response to LPS stimulation. ResultsOur global differential gene expression and pathway impact analyses identified 490 differentially expressed genes and 46 significantly perturbed KEGG pathways, recapitulating known LPS-induced inflammatory responses and identifying two novel signaling pathways, (e.g., SNARE interactions in vesicular transport and the mRNA surveillance pathways). Differential alternative splicing analysis revealed critical impacts on immune-related pathways, including Toll-like receptor signaling, PI3K/AKT signaling, and pro-inflammatory macrophage polarization. Notably, we identified alternative splicing events in genes such as MyD88 and TLR4, which play key roles in terminating inflammatory signaling, as well as splicing of long non-coding RNAs (e.g., MALAT1, PVT1) with potential regulatory functions in immune responses. DiscussionThis study is the first transcriptome-wide characterization of alternative splicing in response to LPS stimulation in PBMCs. Our findings suggest that alternative splicing is a fundamental regulatory mechanism in the inflammatory response and provides potential targets for therapeutic intervention in immune-related conditions.

immunology↗