Single-cell RNA sequencing as well as bulk RNA sequencing data provide valuable insights into both physiological and pathological processes. The effective interpretation of these data relies on the availability of sophisticated analysis and visualization tools. Here, we introduce ClusterGVis, an advanced bioinformatics software specifically designed to simplify the analysis and visualization of gene expression data. ClusterGVis provides a user-friendly interface that allows researchers to perform fuzzy c-means and k-means clustering on transcriptomic datasets. It enables researchers to uncover patterns and relationships within complex gene expression profiles effectively. The integrated heatmap visualization features support intuitive exploration of co-expression networks and the identification of differentially expressed genes across diverse experimental conditions. ClusterGVis serves a dual purpose by aiding in the identification of potential biomarkers and enriching the understanding of gene function and regulatory mechanisms. The tutorials, manual, source code, and demo data of ClusterGVis are publicly available at https://github.com/junjunlab/ClusterGVis and https://bioconductor.org/packages/ClusterGVis. The ClusterGVis Shiny App has been deployed on shinyapps.io and is accessible at https://laojunjun.shinyapps.io/clustergvis_app_v0/. The Shiny App source code is hosted on GitHub at https://github.com/junjunlab/ClusterGvis-app.

Streamlining the clustering and visualization of time-series gene expression data from RNA-Seq experiments, this tool supports fuzzy c-means and k-means clustering algorithms. It is compatible with outputs from widely-used packages such as 'Seurat', 'Monocle', and 'WGCNA', enabling seamless downstream visualization and analysis. See Lokesh Kumar and Matthias E Futschik (2007) for more details.

Biallelic pathogenic variants in METTL5, which encodes an RNA methyltransferase involved in the m⁶A modification of 18S rRNA, have been reported as a rare etiology of autosomal recessive intellectual disability (ID). However, However, the clinical relevance of heterozygous variants in this gene remains unclear. In this study, we report a heterozygous frameshift variant located in exon 1 of the METTL5 gene identified in a father and son presenting with ID. Functional analyses demonstrated that this variant abolishes conserved domains, markedly reduces protein expression, and impairs 18S rRNA m⁶A modification, accompanied by decreased global protein synthesis. Proteomic profiling further revealed a downregulation of neuronal proteins involved in neuron projection, providing biological evidence supporting a potential role of METTL5 haploinsufficiency in neurodevelopmental processes. These observations suggest that heterozygous loss-of-function variants in METTL5, particularly those occurring early in the coding sequence, may be associated with an increased risk of neurodevelopmental disorders. Taken together, our study expands the mutational and phenotypic spectrum of METTL5-related disorders.

Although non–small cell lung cancer (NSCLC) is among the most prevalent malignancies, currently available treatments remain largely ineffective, highlighting the need to elucidate the precise mechanisms of tumorigenesis. The Mpr1/Pad1 N-terminal domain-containing protein (MPND) is a member of the JAMM family of deubiquitinases. In this study, we found that MPND is frequently deleted, and its expression is significantly downregulated in NSCLC tumor tissues. Low MPND levels correlated with poor clinical outcomes, and depletion of MPND enhanced cell migration, invasion, and cancer stem cell–like characteristics in NSCLC cells. Mechanistically, MPND interacted with histones, removing the ubiquitin moiety from monoubiquitinated histone H2A K119 and H2B K120 (H2B K120ub). Loss of MPND elevated the ubiquitination marks, leading to alterations in chromatin architecture. Furthermore, MPND modulated gene transcription, and its depletion activated the transforming growth factor-beta (TGFβ)/SMAD3 signaling pathway. Specifically, the knockout of MPND increased H2B K120ub and chromatin accessibility at the SMAD3 locus, facilitating transcriptional activation. In mouse tumor models and clinical samples from patients with NSCLC, the loss of MPND consistently triggered activation of the TGFβ/SMAD3 axis, thereby promoting tumor growth and metastasis. Together, these data reveal an epigenetic pathway underlying NSCLC progression and suggest that targeting the TGFβ/SMAD3 axis may be particularly effective for the treatment of MPND-deficient NSCLC tumors. Significance: Loss of MPND in lung cancer promotes tumor growth and metastasis by increasing histone ubiquitination to epigenetically activate TGFβ/SMAD3 signaling, suggesting that targeting this axis may provide therapeutic benefit in MPND-deficient tumors.