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.

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.

Background: Cisplatin resistance remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been implicated in chemotherapy resistance, their specific roles and underlying mechanisms remain incompletely understood. This study aimed to identify lncRNAs associated with cisplatin resistance in NSCLC and to elucidate the role and mechanism of NR2F1-AS1 (NAS1) in this process. Methods: Cisplatin-resistant NSCLC cell lines were established and subjected to transcriptome-wide RNA sequencing. NAS1 expression was validated by quantitative real-time PCR, and its clinical relevance was assessed using The Cancer Genome Atlas (TCGA) dataset. NAS1 and NR2F1 knockdown, together with NR2F1 overexpression and rescue experiments, were performed to evaluate their effects on cisplatin sensitivity. Downstream mechanisms were investigated by public dataset analysis, qPCR, and Western blotting, and NF-κB signaling was functionally assessed using the inhibitor DHMEQ. Results:NAS1 was consistently downregulated in multiple cisplatin-resistant NSCLC cell lines and was also decreased in NSCLC tissues. NAS1 knockdown enhanced cisplatin resistance. Mechanistically, loss of NAS1 reduced NR2F1 protein expression without significantly affecting its mRNA level, indicating translational regulation. NR2F1 downregulation also conferred cisplatin resistance, phenocopying the effect of NAS1 loss, whereas NR2F1 re-expression restored cisplatin sensitivity. Further analyses identified TGFB1 as a downstream effector derepressed by loss of the NAS1-NR2F1 axis, leading to activation of NF-κB signaling. Inhibition of NF-κB partially reversed cisplatin resistance in resistant cells. Conclusions: Collectively, our findings delineate a NAS1/NR2F1/TGFB1/NF-κB signaling axis critical for cisplatin resistance in NSCLC, revealing a potential therapeutic target for overcoming platinum resistance.