School of Electrical and Information Engineering, Zhengzhou University, Zhengzhou 450001, China.
State Key Laboratory of Intelligent Agricultural Power Equipment, Zhengzhou University, Luoyang 471000, China.
Brief Bioinform. 2023 Sep 22;24(6). doi: 10.1093/bib/bbad364.
Considering that cancer is resulting from the comutation of several essential genes of individual patients, researchers have begun to focus on identifying personalized edge-network biomarkers (PEBs) using personalized edge-network analysis for clinical practice. However, most of existing methods ignored the optimization of PEBs when multimodal biomarkers exist in multi-purpose early disease prediction (MPEDP). To solve this problem, this study proposes a novel model (MMPDENB-RBM) that combines personalized dynamic edge-network biomarkers (PDENB) theory, multimodal optimization strategy and latent space search scheme to identify biomarkers with different configurations of PDENB modules (i.e. to effectively identify multimodal PDENBs). The application to the three largest cancer omics datasets from The Cancer Genome Atlas database (i.e. breast invasive carcinoma, lung squamous cell carcinoma and lung adenocarcinoma) showed that the MMPDENB-RBM model could more effectively predict critical cancer state compared with other advanced methods. And, our model had better convergence, diversity and multimodal property as well as effective optimization ability compared with the other state-of-art methods. Particularly, multimodal PDENBs identified were more enriched with different functional biomarkers simultaneously, such as tissue-specific synthetic lethality edge-biomarkers including cancer driver genes and disease marker genes. Importantly, as our aim, these multimodal biomarkers can perform diverse biological and biomedical significances for drug target screen, survival risk assessment and novel biomedical sight as the expected multi-purpose of personalized early disease prediction. In summary, the present study provides multimodal property of PDENBs, especially the therapeutic biomarkers with more biological significances, which can help with MPEDP of individual cancer patients.
考虑到癌症是个体患者的几个关键基因的突变导致的,研究人员已开始专注于使用个性化边缘网络分析来识别个性化边缘网络生物标志物(PEBs),以用于临床实践。然而,在多用途早期疾病预测(MPEDP)中存在多种模态生物标志物时,大多数现有方法忽略了 PEBs 的优化。为了解决这个问题,本研究提出了一种新模型(MMPDENB-RBM),它结合了个性化动态边缘网络生物标志物(PDENB)理论、多模态优化策略和潜在空间搜索方案,以识别具有不同 PDENB 模块配置的生物标志物(即有效识别多模态 PDENBs)。该模型在来自癌症基因组图谱数据库(即乳腺浸润性癌、肺鳞癌和肺腺癌)的三个最大的癌症组学数据集上的应用表明,与其他先进方法相比,MMPDENB-RBM 模型可以更有效地预测关键的癌症状态。而且,与其他最先进的方法相比,我们的模型具有更好的收敛性、多样性和多模态特性以及有效的优化能力。特别是,所识别的多模态 PDENBs 同时更丰富地包含了不同的功能生物标志物,例如包括癌症驱动基因和疾病标记基因的组织特异性合成致死性边缘生物标志物。重要的是,正如我们的目标,这些多模态生物标志物可以为药物靶标筛选、生存风险评估和新的生物医学视角提供多样化的生物学和生物医学意义,作为个性化早期疾病预测的预期多用途。总之,本研究提供了 PDENB 的多模态特性,特别是具有更多生物学意义的治疗生物标志物,这有助于个体癌症患者的 MPEDP。