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Deep Learning-Based Multi-Omics Data Integration Reveals Two Prognostic Subtypes in High-Risk Neuroblastoma

机译:基于深度学习的多OMICS数据集成揭示了高风险神经母细胞瘤中的两种预后亚型

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摘要

High-risk neuroblastoma is a very aggressive disease, with excessive tumor growth and poor outcomes. A proper stratification of the high-risk patients by prognostic outcome is important for treatment. However, there is still a lack of survival stratification for the high-risk neuroblastoma. To fill the gap, we adopt a deep learning algorithm, Autoencoder, to integrate multi-omics data, and combine it with K-means clustering to identify two subtypes with significant survival differences. By comparing the Autoencoder with PCA, iCluster, and DGscore about the classification based on multi-omics data integration, Autoencoder-based classification outperforms the alternative approaches. Furthermore, we also validated the classification in two independent datasets by training machine-learning classification models, and confirmed its robustness. Functional analysis revealed that MYCN amplification was more frequently occurred in the ultra-high-risk subtype, in accordance with the overexpression of MYC/MYCN targets in this subtype. In summary, prognostic subtypes identified by deep learning-based multi-omics integration could not only improve our understanding of molecular mechanism, but also help the clinicians make decisions.
机译:高风险的神经母细胞瘤是一种非常侵略性的疾病,肿瘤过度增长和差的结果。通过预后结果对高危患者的适当分层是对治疗的重要性。然而,高危神经母细胞瘤仍然缺乏生存分层。为了填补差距,我们采用深度学习算法,自动探测器,集成多个OMICS数据,并将其与K-Means群集组合以识别两个具有显着生存差异的亚型。通过将AutoEncoder与PCA,ICLUSTER和DGSCORE进行比较,基于多OMICS数据集成的分类,基于AutoEncoder的分类优越替代方法。此外,我们还通过培训机器学习分类模型来验证两个独立数据集的分类,并确认其稳健性。功能分析表明,根据该亚型中的Myc / Mycn靶的过度表达,在超高危亚型中更频繁地发生MyCN扩增。总之,基于深度学习的多OMICS集成确定的预后亚型不仅可以提高我们对分子机制的理解,而且还可以帮助临床医生做出决定。

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