Personalized treatment selection via product partition models with covariates.

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.

Clustering blood donors via mixtures of product partition models with covariates.

Motivated by the problem of accurately predicting gap times between successive blood donations, we present here a general class of Bayesian nonparametric models for clustering. These models allow for the prediction of new recurrences, accommodating covariate information that describes the personal characteristics of the sample individuals. We introduce a prior for the random partition of the sample individuals, which encourages two individuals to be co-clustered if they have similar covariate values. Our prior generalizes product partition models with covariates (PPMx) models in the literature, which are defined in terms of cohesion and similarity functions. We assume cohesion functions that yield mixtures of PPMx models, while our similarity functions represent the denseness of a cluster. We show that including covariate information in the prior specification improves the posterior predictive performance and helps interpret the estimated clusters in terms of covariates in the blood donation application.

Hierarchical Normalized Completely Random Measures for Robust Graphical Modeling.

Gaussian graphical models are useful tools for exploring network structures in multivariate normal data. In this paper we are interested in situations where data show departures from Gaussianity, therefore requiring alternative modeling distributions. The multivariate t-distribution, obtained by dividing each component of the data vector by a gamma random variable, is a straightforward generalization to accommodate deviations from normality such as heavy tails. Since different groups of variables may be contaminated to a different extent, Finegold and Drton (2014) introduced the Dirichlet t-distribution, where the divisors are clustered using a Dirichlet process. In this work, we consider a more general class of nonparametric distributions as the prior on the divisor terms, namely the class of normalized completely random measures (NormCRMs). To improve the effectiveness of the clustering, we propose modeling the dependence among the divisors through a nonparametric hierarchical structure, which allows for the sharing of parameters across the samples in the data set. This desirable feature enables us to cluster together different components of multivariate data in a parsimonious way. We demonstrate through simulations that this approach provides accurate graphical model inference, and apply it to a case study examining the dependence structure in radiomics data derived from The Cancer Imaging Atlas.

An integrative Bayesian Dirichlet-multinomial regression model for the analysis of taxonomic abundances in microbiome data.

BACKGROUND: The Human Microbiome has been variously associated with the immune-regulatory mechanisms involved in the prevention or development of many non-infectious human diseases such as autoimmunity, allergy and cancer. Integrative approaches which aim at associating the composition of the human microbiome with other available information, such as clinical covariates and environmental predictors, are paramount to develop a more complete understanding of the role of microbiome in disease development. RESULTS: In this manuscript, we propose a Bayesian Dirichlet-Multinomial regression model which uses spike-and-slab priors for the selection of significant associations between a set of available covariates and taxa from a microbiome abundance table. The approach allows straightforward incorporation of the covariates through a log-linear regression parametrization of the parameters of the Dirichlet-Multinomial likelihood. Inference is conducted through a Markov Chain Monte Carlo algorithm, and selection of the significant covariates is based upon the assessment of posterior probabilities of inclusions and the thresholding of the Bayesian false discovery rate. We design a simulation study to evaluate the performance of the proposed method, and then apply our model on a publicly available dataset obtained from the Human Microbiome Project which associates taxa abundances with KEGG orthology pathways. The method is implemented in specifically developed R code, which has been made publicly available. CONCLUSIONS: Our method compares favorably in simulations to several recently proposed approaches for similarly structured data, in terms of increased accuracy and reduced false positive as well as false negative rates. In the application to the data from the Human Microbiome Project, a close evaluation of the biological significance of our findings confirms existing associations in the literature.