论文标题

通过与协变量的产品分区模型进行个性化治疗选择

Personalized Treatment Selection via Product Partition Models with Covariates

论文作者

Pedone, Matteo, Argiento, Raffaele, Stingo, Francesco C.

论文摘要

精密医学是一种疾病治疗的方法,可以根据患者的个体特征来定义治疗策略。由癌症基因组学中的开放问题的动机,我们开发了一种新型模型,该模型灵活地促进具有相似预测特征和相似治疗反应的患者。这种方法通过预测推断确定了这一套治疗方法中的一种更适合新患者。所提出的方法是完全基于模型的,避免了通过采用启发式聚类程序执行治疗分配而获得的不确定性低估,并且属于具有协变量的产品分配模型的类别,此处扩展到包括正常化的广义Gamma过程所诱导的凝聚力。该方法在模拟研究中预测协变量的相当异质性的情况下,该方法的表现尤其出色。癌症基因组学案例研究说明了所提出方法产生的治疗反应的潜在益处。最后,作为基于模型的方法,该方法允许估计簇的特定反应概率,然后识别患者从个性化治疗中受益更可能受益。

Precision medicine is an approach for disease treatment that defines treatment strategies based on the individual characteristics of the patients. Motivated by an open problem in cancer genomics, we develop a novel model that flexibly clusters patients with similar predictive characteristics and similar treatment responses; this approach identifies, via predictive inference, which one among a set of treatments is better suited for a new patient. The proposed method is fully model-based, avoiding uncertainty underestimation attained when treatment assignment is performed by adopting heuristic clustering procedures, and belongs to the class of product partition models with covariates, here extended to include the cohesion induced by the Normalized Generalized Gamma process. The method performs particularly well in scenarios characterized by considerable heterogeneity of the predictive covariates in simulation studies. A cancer genomics case study illustrates the potential benefits in terms of treatment response yielded by the proposed approach. Finally, being model-based, the approach allows estimating clusters' specific response probabilities and then identifying patients more likely to benefit from personalized treatment.

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