bioRxiv ScienceSearch

bioRxiv · 10.1101/543835

Identification of key genes and pathways associated with Crohn's disease by bioinformatics analysis

Abstract

Crohns disease is a type of inflammatory bowel disease posing a significant threat to human health all over the world. Genome-wide gene expression profiles of mucosal colonic biopsies have provided some insight into the molecular mechanisms of Crohns disease. However, the exact pathogenesis is unclear. This study aimed to identify key genes and significant signaling pathways associated with Crohns disease by bioinformatics analysis. To identify key genes, an integrated analysis of gene expression signature was conducted using a robust rank aggregation approach. A total of 179 Crohns disease patients and 94 healthy controls from nine public microarray datasets were included. MMP1 and CLDN8 were two key genes screened from the differentially expressed genes. Connectivity Map predicted several small molecules as possible adjuvant drugs to treat CD. Besides, we used weighted gene co-expression network analysis to explore the co-expression modules associated with Crohns disease pathogenesis. Seven main functional modules were identified, of which black module showed the highest correlation with Crohns disease. The genes in black module mainly enriched in Interferon Signaling and defense response to virus. Blue module was another important module and enriched in several signaling pathways, including extracellular matrix organization, inflammatory response and blood vessel development. There were also several other meaningful functional modules which enriched in many biological processes. The present study identified a number of key genes and pathways correlated with Crohns disease and potential drugs to combat it, which might offer insights into Crohns disease pathogenesis and provide a clue to potential treatments.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Wang, Z., Zhu, J., Ma, L.. 2019-02-07. Identification of key genes and pathways associated with Crohn's disease by bioinformatics analysis. https://doi.org/10.1101/543835

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

KEEP EXPLORING

Related preprints

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

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

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