Hong Wang, Yi Zhang, Wen Li, Zhen Wei, Zhenlong Wang, Mengyuan Yang
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CLCluster: A redundancy-reduction contrastive learning-based clustering method of cancer subtype based on multi-omics data.
Alternative splicing (AS) allows one gene to produce several protein variants, offering valuable predictive insights into cancer and facilitating targeted therapies. Although multi-omics data are used to identify cancer subtypes, AS is rarely utilized for this purpose. Here, we propose a redundancy-reduction contrastive learning-based method (CLCluster) based on copy number variation, methylation, gene expression, miRNA expression, and AS for cancer subtype clustering of 33 cancer types. Ablation experiments emphasize the benefits of using AS data to subtype cancer. We identified 2,921 cancer subtype-related AS events associated with patient survival and conducted multiple analyses including open reading frame annotation, RNA binding protein (RBP)-associated AS regulation, and splicing-related anticancer peptides (ACPs) prediction for therapeutic biomarkers. The CLCluster model is more effective in identifying prognostic-relevant cancer subtypes than other models. The effective annotation of cancer subtype related AS events facilitates the identification of therapeutically targetable biomarkers in patients.
期刊介绍:
Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.