RESUMO
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.
Assuntos
Modelos Estatísticos , Neoplasias , Humanos , Medicina de Precisão/métodos , Probabilidade , Simulação por Computador , Neoplasias/genética , Neoplasias/terapia , Teorema de BayesRESUMO
We develop a scalable multi-step Monte Carlo algorithm for inference under a large class of nonparametric Bayesian models for clustering and classification. Each step is "embarrassingly parallel" and can be implemented using the same Markov chain Monte Carlo sampler. The simplicity and generality of our approach makes inference for a wide range of Bayesian nonparametric mixture models applicable to large datasets. Specifically, we apply the approach to inference under a product partition model with regression on covariates. We show results for inference with two motivating data sets: a large set of electronic health records (EHR) and a bank telemarketing dataset. We find interesting clusters and competitive classification performance relative to other widely used competing classifiers. Supplementary materials for this article are available online.