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用于预测癌症免疫治疗反应生存情况的集成可解释机器学习与多组学分析

Integrated explainable machine learning and multi-omics analysis for survival prediction in cancer with immunotherapy response.

作者信息

Hounye Alphonse Houssou, Xiong Li, Hou Muzhou

机构信息

General surgery department of Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, China.

School of Mathematics and Statistics, Central South University, Changsha, 410083, China.

出版信息

Apoptosis. 2025 Feb;30(1-2):364-388. doi: 10.1007/s10495-024-02050-4. Epub 2024 Dec 4.

Abstract

To demonstrate the efficacy of machine learning models in predicting mortality in melanoma cancer, we developed an interpretability model for better understanding the survival prediction of cancer. To this end, the optimal features were identified, ten different machine learning models were utilized to predict mortality across various datasets. Then we have utilized the important features identified by those machines learning methods to construct a new model named NKECLR to forecast mortality of patient with cancer. To explicitly clarify the model's decision-making process and uncover novel findings, an interpretable technique incorporating machine learning and SHapley Additive exPlanations (SHAP), as well as LIME, has been employed, and four genes EPGN, PHF11, RBM34, and ZFP36 were identified from those machine learning(ML). The experimental analysis conducted on training and validation datasets demonstrated that the proposed model has a good performance com- pared to existing methods with AUC value 81.8%, and 79.3%, respectively. Moreover, when combined our NKECLR with PD-L1, PD-1, and CTLA-4 the AUC value was 83%0. Finally, these findings have been applied to comprehend the response of drugs and immunotherapy. Our research introduced an innovative predictive NKECLR model utilizing natural killer(NK) cell marker genes for cohorts with melanoma cancer. The NKECLR model can effectively predict the survival of melanoma cancer cohorts and treatment results, revealing distinct immune cell infiltration in the high-risk group.

摘要

为了证明机器学习模型在预测黑色素瘤死亡率方面的有效性,我们开发了一种可解释性模型,以更好地理解癌症的生存预测。为此,我们确定了最佳特征,利用十种不同的机器学习模型对各种数据集的死亡率进行预测。然后,我们利用这些机器学习方法识别出的重要特征构建了一个名为NKECLR的新模型,以预测癌症患者的死亡率。为了明确阐明模型的决策过程并发现新的结果,我们采用了一种将机器学习与SHapley Additive exPlanations(SHAP)以及LIME相结合的可解释技术,并从这些机器学习(ML)中识别出四个基因EPGN、PHF11、RBM34和ZFP36。在训练和验证数据集上进行的实验分析表明,与现有方法相比,所提出的模型具有良好的性能,AUC值分别为81.8%和79.3%。此外,当将我们的NKECLR与PD-L1、PD-1和CTLA-4联合使用时,AUC值为83%。最后,这些发现已被应用于理解药物和免疫疗法的反应。我们的研究引入了一种创新的预测性NKECLR模型,该模型利用自然杀伤(NK)细胞标记基因对黑色素瘤患者队列进行研究。NKECLR模型可以有效地预测黑色素瘤患者队列的生存率和治疗结果,揭示高危组中不同的免疫细胞浸润情况。

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