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An efficient graph attention framework enhances bladder cancer prediction

基因 计算生物学 癌变 膀胱癌 恶性肿瘤 癌症 生物 遗传学 计算机科学 生物信息学
作者
Taghreed S. Ibrahim,Mohamed S. Saraya,Ahmed I. Saleh,Asmaa H. Rabie
出处
期刊:Scientific Reports [Nature Portfolio]
卷期号:15 (1): 11127-11127 被引量:2
标识
DOI:10.1038/s41598-025-93059-5
摘要

Bladder (BL) cancer is the 10th most common cancer worldwide, ranking 9th in males and 13th in females in the United States, respectively. BL cancer is a quick-growing tumor of all cancer forms. Given a malignant tumor's high malignancy, rapid metastasis prediction and accurate treatment are critical. The most significant drivers of the intricate genesis of cancer are complex genetics, including deoxyribonucleic acid (DNA) insertions and deletions, abnormal structure, copy number variations (CNVs), and single nucleotide variations (SNVs). The proposed method enhances the identification of driver genes at the individual patient level by employing attention mechanisms to extract features of both coding and non-coding genes and predict BL cancer based on the personalized driver gene (PDG) detection. The embedded vectors are propagated through the three dense blocks for the binary classification of PDGs. The novel constructure of graph neural network (GNN) with attention mechanism, called Multi Stacked-Layered GAT (MSL-GAT) leverages graph attention mechanisms (GAT) to identify and predict critical driver genes associated with BL cancer progression. In order to pick out and extract essential features from both coding and non-coding genes, including long non-coding RNAs (lncRNAs), which are known to be crucial to the advancement of BL cancer. The approach analyzes key genetic changes (such as SNVs, CNVs, and structural abnormalities) that lead to tumorigenesis and metastasis by concentrating on personalized driver genes (PDGs). The discovery of genes crucial for the survival and proliferation of cancer cells is made possible by the model's precise classification of PDGs. MSL-GAT draws attention to certain lncRNAs and other non-coding elements that control carcinogenic pathways by utilizing the attention mechanism. Tumor development, metastasis, and medication resistance are all facilitated by these lncRNAs, which are frequently overexpressed or dysregulated in BL cancer. In order to reduce the survival of cancer cells, the model's predictions can direct specific treatment approaches, such as RNA interference (RNAi), to mute or suppress the expression of these important genes. MSL-GAT is followed by three dense blocks that spread the embedded vectors to categorize PDGs, making it possible to determine which genes are more likely to cause BL cancer in a certain patient. The model facilitates the identification of new treatment targets by offering a thorough understanding of the molecular landscape of BL cancer through the integration of multi-omics data, encompassing as genomic, transcriptomic, and epigenomic metadata. We compared the novel approach with classical machine learning methods and other deep learning-based methods on benchmark TCGA-BLCA, and the leave-one-out experimental results showed that MSL-GAT achieved better performance than competitive methods. This approach achieves accuracy with 97.72% and improves specificity and sensitivity. It can potentially aid physicians during early prediction of BL cancer.
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