Bayesian approaches to designing replication studies.

Replication studies are essential for assessing the credibility of claims from original studies. A critical aspect of designing replication studies is determining their sample size; a too-small sample size may lead to inconclusive studies whereas a too-large sample size may waste resources that could be allocated better in other studies. Here, we show how Bayesian approaches can be used for tackling this problem. The Bayesian framework allows researchers to combine the original data and external knowledge in a design prior distribution for the underlying parameters. Based on a design prior, predictions about the replication data can be made, and the replication sample size can be chosen to ensure a sufficiently high probability of replication success. Replication success may be defined by Bayesian or non-Bayesian criteria and different criteria may also be combined to meet distinct stakeholders and enable conclusive inferences based on multiple analysis approaches. We investigate sample size determination in the normal-normal hierarchical model where analytical results are available and traditional sample size determination is a special case where the uncertainty on parameter values is not accounted for. We use data from a multisite replication project of social-behavioral experiments to illustrate how Bayesian approaches can help design informative and cost-effective replication studies. Our methods can be used through the R package BayesRepDesign. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Bayesian graphical modeling for heterogeneous causal effects.

There is a growing interest in current medical research to develop personalized treatments using a molecular-based approach. The broad goal is to implement a more precise and targeted decision-making process, relative to traditional treatments based primarily on clinical diagnoses. Specifically, we consider patients affected by Acute Myeloid Leukemia (AML), an hematological cancer characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Because AML responds poorly to chemotherapeutic treatments, the development of targeted therapies is essential to improve patients' prospects. In particular, the dataset we analyze contains the levels of proteins involved in cell cycle regulation and linked to the progression of the disease. We evaluate treatment effects within a causal framework represented by a Directed Acyclic Graph (DAG) model, whose vertices are the protein levels in the network. A major obstacle in implementing the above program is represented by individual heterogeneity. We address this issue through a Dirichlet Process (DP) mixture of Gaussian DAG-models where both the graphical structure as well as the allied model parameters are regarded as uncertain. Our procedure determines a clustering structure of the units reflecting the underlying heterogeneity, and produces subject-specific estimates of causal effects based on Bayesian Model Averaging (BMA). With reference to the AML dataset, we identify different effects of protein regulation among individuals; moreover, our method clusters patients into groups that exhibit only mild similarities with traditional categories based on morphological features.

Bayesian inference of causal effects from observational data in Gaussian graphical models.

We assume that multivariate observational data are generated from a distribution whose conditional independencies are encoded in a Directed Acyclic Graph (DAG). For any given DAG, the causal effect of a variable onto another one can be evaluated through intervention calculus. A DAG is typically not identifiable from observational data alone. However, its Markov equivalence class (a collection of DAGs) can be estimated from the data. As a consequence, for the same intervention a set of causal effects, one for each DAG in the equivalence class, can be evaluated. In this paper, we propose a fully Bayesian methodology to make inference on the causal effects of any intervention in the system. Main features of our method are: (a) both uncertainty on the equivalence class and the causal effects are jointly modeled; (b) priors on the parameters of the modified Cholesky decomposition of the precision matrices across all DAG models are constructively assigned starting from a unique prior on the complete (unrestricted) DAG; (c) an efficient algorithm to sample from the posterior distribution on graph space is adopted; (d) an objective Bayes approach, requiring virtually no user specification, is used throughout. We demonstrate the merits of our methodology in simulation studies, wherein comparisons with current state-of-the-art procedures turn out to be highly satisfactory. Finally we examine a real data set of gene expressions for Arabidopsis thaliana.

Bayesian learning of multiple directed networks from observational data.

Graphical modeling represents an established methodology for identifying complex dependencies in biological networks, as exemplified in the study of co-expression, gene regulatory, and protein interaction networks. The available observations often exhibit an intrinsic heterogeneity, which impacts on the network structure through the modification of specific pathways for distinct groups, such as disease subtypes. We propose to infer the resulting multiple graphs jointly in order to benefit from potential similarities across groups; on the other hand our modeling framework is able to accommodate group idiosyncrasies. We consider directed acyclic graphs (DAGs) as network structures, and develop a Bayesian method for structural learning of multiple DAGs. We explicitly account for Markov equivalence of DAGs, and propose a suitable prior on the collection of graph spaces that induces selective borrowing strength across groups. The resulting inference allows in particular to compute the posterior probability of edge inclusion, a useful summary for representing flow directions within the network. Finally, we detail a simulation study addressing the comparative performance of our method, and present an analysis of two protein networks together with a substantive interpretation of our findings.

The Measure of Population Aging in Different Welfare Regimes: A Bayesian Dynamic Modeling Approach.

Given a population at a specific time point, it is often of interest to identify the entry age into typical stages of life, such as being young, becoming adult and elderly. These age cutoffs are important because they influence the public opinion and have an impact on policy decisions. An issue of great social relevance is defining the threshold beyond which a person becomes elderly. Fixed cutoffs are debatable because of their conventional nature which disregards issues such as changing life expectancy and the evolving structure of the age distribution. The above shortcomings can be overcome if age cutoffs are defined endogenously, i.e., relative to the whole age distribution of each country at a specific time point. We pursue this line of research by presenting an analysis whose main features are: (1) establishing a relationship between a country's welfare regime and its age distribution and aging process, together with the identification of four clusters of countries corresponding to distinctive welfare models and (2) a Bayesian hierarchical dynamic model which accounts for the uncertainty in the time series of measurements of the endogenous cutoffs for the countries in the sample, as well as for their clustering structure. Our analysis leads to model-based estimates of country-specific endogenous age cutoffs and corresponding aging indicators. Additionally, we provide cluster-specific estimates, a novel contribution engendered by the use of hierarchical modeling, which widens the scope of our analysis beyond the countries which are present in the sample.

Objective Bayesian Comparison of Constrained Analysis of Variance Models.

In the social sciences we are often interested in comparing models specified by parametric equality or inequality constraints. For instance, when examining three group means [Formula: see text] through an analysis of variance (ANOVA), a model may specify that [Formula: see text], while another one may state that [Formula: see text], and finally a third model may instead suggest that all means are unrestricted. This is a challenging problem, because it involves a combination of nonnested models, as well as nested models having the same dimension. We adopt an objective Bayesian approach, requiring no prior specification from the user, and derive the posterior probability of each model under consideration. Our method is based on the intrinsic prior methodology, suitably modified to accommodate equality and inequality constraints. Focussing on normal ANOVA models, a comparative assessment is carried out through simulation studies. We also present an application to real data collected in a psychological experiment.

Objective Bayesian search of Gaussian directed acyclic graphical models for ordered variables with non-local priors.

Directed acyclic graphical (DAG) models are increasingly employed in the study of physical and biological systems to model direct influences between variables. Identifying the graph from data is a challenging endeavor, which can be more reasonably tackled if the variables are assumed to satisfy a given ordering; in this case we simply have to estimate the presence or absence of each potential edge. Working under this assumption, we propose an objective Bayesian method for searching the space of Gaussian DAG models, which provides a rich output from minimal input. We base our analysis on non-local parameter priors, which are especially suited for learning sparse graphs, because they allow a faster learning rate, relative to ordinary local parameter priors, when the true unknown sampling distribution belongs to a simple model. We implement an efficient stochastic search algorithm, which deals effectively with data sets having sample size smaller than the number of variables, and apply our method to a variety of simulated and real data sets. Our approach compares favorably, in terms of the ROC curve for edge hit rate versus false alarm rate, to current state-of-the-art frequentist methods relying on the assumption of ordered variables; under this assumption it exhibits a competitive advantage over the PC-algorithm, which can be considered as a frequentist benchmark for unordered variables. Importantly, we find that our method is still at an advantage for learning the skeleton of the DAG, when the ordering of the variables is only moderately mis-specified. Prospectively, our method could be coupled with a strategy to learn the order of the variables, thus dropping the known ordering assumption.

Testing Hardy-Weinberg equilibrium: an objective Bayesian analysis.

We analyze the general (multiallelic) Hardy-Weinberg equilibrium problem from an objective Bayesian testing standpoint. We argue that for small or moderate sample sizes the answer is rather sensitive to the prior chosen, and this suggests to carry out a sensitivity analysis with respect to the prior. This goal is achieved through the identification of a class of priors specifically designed for this testing problem. In this paper, we consider the class of intrinsic priors under the full model, indexed by a tuning quantity, the training sample size. These priors are objective, satisfy Savage's continuity condition and have proved to behave extremely well for many statistical testing problems. We compute the posterior probability of the Hardy-Weinberg equilibrium model for the class of intrinsic priors, assess robustness over the range of plausible answers, as well as stability of the decision in favor of either hypothesis.