bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.12.05.570305

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Vastrad, B. M.·Vastrad, C. M.
View original source ↗Export metadata ↓

Abstract

Multiple sclerosis (MS) is an autoinflammatory disease that might lead to severe disability. The diagnosis of MS is defined due to the urgency for biomarkers with both reliability and efficiency. Demyelination of axons are deeply involved in the pathogenesis of MS. Our study aims to identify the underlying molecular mechanism and screening for related biomarkers and signaling pathways. We obtained next generation sequencing (NGS) dataset (GSE138614) from the GEO database. Differentially expressed genes (DEGs) were screened by the DESeq2 package in R bioconductor with considering specific criteria. Gene Ontology (GO) enrichment analysis, REACTOME pathway enrichment analysis were performed; a protein-protein interaction (PPI) network was constructed; significant modules were analyzed and hub genes were identified by Human Integrated Protein-Protein Interaction rEference (HiPPIE). Subsequently, miRNA-hub gene regulatory network, TF-hub gene regulatory network and drug-hub gene interaction network were built by Cytoscape to predict the underlying microRNAs (miRNAs), transcription factors (TFs) and drugs associated with hub genes. Receiver operating characteristic (ROC) curves analysis was performed to calculate diagnostic value of hub genes. Finally, we performed molecular docking study for prediction of drug molecules against protein targets. A total of 959 DEGs (479 up-regulated and 480 down-regulated genes) were identified in the MS samples and compared with normal control samples. The DEGs were predominantly enriched in an ensemble of genes encoding the immune system process, developmental process, immune system and regulation of cholesterol biosynthesis by SREBP (SREBF). A PPI network was obtained through HiPPIE analysis, and the results were imported into Cytoscape software. The DEGs were sequenced by the Network Analyzer plug-in by various calculation methods, and 10 hub genes (LCK, PYHIN1, SLAMF1, DOK2, TAB2, CFTR, RHOB, LMNA, EGLN3 and ERBB3) were finally selected. Based on the miRNA-hub gene regulatory network and TF-hub gene regulatory network construction, miRNAs including hsa-mir-6794-3p, hsa-mir-3689a-3p, hsa-mir-4651, hsa-mir-548q, BRCA1, HNF4A, TFAP2C and NR2F1 were determined to be potential key biomarkers. Drug-hub gene interaction network constructed from DrugBank, which identified targeted therapeutic drugs (Palivizumab, Cu-Bicyclam, Lumacaftor and Zonisamide) for the hub genes. From molecular docking study we showed good drug - protein bind affinity and amino acid interactions. This study identified novel biomarkers for MS and established a reliable diagnostic model as well as predicted novel drug molecules. The transcriptional changes identified may help to reveal the pathogenesis and molecular mechanisms of MS.

Explore related subjects

bioinformaticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Vastrad, B. M., Vastrad, C. M.. 2023-12-07. Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis. https://doi.org/10.1101/2023.12.05.570305

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics↗
bioRxiv2026

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics↗
bioRxiv2026

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics↗