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Accurate classification of cancer subtypes plays a pivotal role in advancing precision medicine. In this study, we introduce WMRCA + , a novel clustering approach based on a weighted majority rule that integrates multi-omics data and incorporates metabolic gene sets to robustly determine the optimal number of clusters for tumor subtype identification. WMRCA + evaluates clustering performance using ten internal metrics and offers comprehensive functionalities for data preprocessing and visualization. When applied to The Cancer Genome Atlas (TCGA) lung cancer dataset using lipid metabolism-related gene sets, WMRCA + outperformed widely used clustering algorithms-including iCluster, SNF, NMF, CC, and CNMF-achieving an AUC of 0.947. WMRCA + provides robust, interpretable, and biologically meaningful clustering results, offering a valuable tool for improving the accuracy of cancer subtype prediction. The WMRCA + R package is freely available at https://github.com/guojunliu7/WMRCA .
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http://dx.doi.org/10.1186/s41065-025-00487-4 | DOI Listing |
Genes Immun
September 2025
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Fulham Road, London, UK. Electronic address:
Multiplex assays of variant effect (MAVEs) provide promising new sources of functional evidence, potentially empowering improved classification of germline genomic variants, particularly rare missense variants, which are commonly assigned as variants of uncertain significance (VUSs). However, paradoxically, quantification of clinically applicable evidence strengths for MAVEs requires construction of "truthsets" comprising missense variants already robustly classified as pathogenic and benign. In this study, we demonstrate how benign truthset size is the primary driver of applicable functional evidence toward pathogenicity (PS3).
View Article and Find Full Text PDFPlant J
September 2025
College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, China.
Genome imbalance, resulting from varying the dosage of individual chromosomes (aneuploidy), has a more detrimental effect than changes in complete sets of chromosomes (haploidy/polyploidy). This imbalance is likely due to disruptions in stoichiometry and interactions among macromolecular assemblies. Previous research has shown that aneuploidy causes global modulation of protein-coding genes (PCGs), microRNAs, and transposable elements (TEs), affecting both the varied chromosome (cis-located) and unvaried genome regions (trans-located) across various taxa.
View Article and Find Full Text PDFToxicol Sci
September 2025
Aquatic and Crop Resource Development, National Research Council of Canada, Halifax, NS, B3H 3Z1, Canada.
In the zebrafish larval toxicity model, phenotypic changes induced by chemical exposure can potentially be explained and predicted by the analysis of gene expression changes at sub-phenotypic concentrations. The increase in knowledge of gene pathway-specific effects arising from the zebrafish transcriptomic model has the potential to enhance the role of the larval zebrafish as a component of Integrated Approaches to Testing and Assessment (IATA). In this paper, we compared the transcriptomic responses of triphenyl phosphate between two standard exposure paradigms, the Zebrafish Embryo Toxicity (ZET) and General and Behavioural Toxicity (GBT) assays.
View Article and Find Full Text PDFACS Synth Biol
September 2025
Department of BioSciences, Rice University, MS-140, 6100 Main Street, Houston, Texas 77005, United States.
Microbes can be programmed to record participation in gene transfer by coding biological-recording devices into mobile DNA. Upon DNA uptake, these devices transcribe a catalytic RNA (cat-RNA) that binds to conserved sequences within ribosomal RNAs (rRNAs) and perform a trans-splicing reaction that adds a barcode to the rRNAs. Existing cat-RNA designs were generated to be broad-host range, providing no control over the organisms that were barcoded.
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