Chengchun Shi

A central question in high-dimensional mediation analysis is to infer the significance of individual mediators. The main challenge is that the total number of potential paths that go through any mediator is super-exponential in the number of mediators. Most existing mediation inference solutions either explicitly impose that the mediators are conditionally independent given the exposure, or ignore any potential directed paths among the mediators. In this article, we propose a novel hypothesis testing procedure to evaluate individual mediation effects, while taking into account potential interactions among the mediators. Our proposal thus fills a crucial gap, and greatly extends the scope of existing mediation tests. Our key idea is to construct the test statistic using the logic of Boolean matrices, which enables us to establish the proper limiting distribution under the null hypothesis. We further employ screening, data splitting, and decorrelated estimation to reduce the bias and increase the power of the test. We show that our test can control both the size and false discovery rate asymptotically, and the power of the test approaches one, while allowing the number of mediators to diverge to infinity with the sample size. We demonstrate the efficacy of the method through simulations and a neuroimaging study of Alzheimer’s disease. A Python implementation of the proposed procedure is available at https://github.com/callmespring/LOGAN.

In contrast to the classical “one-size-fits-all” approach, precision medicine proposes the customization of individualized treatment regimes to account for patients’ heterogeneity in response to treatments. Most of existing works in the literature focused on estimating optimal individualized treatment regimes. However, there has been less attention devoted to hypothesis testing regarding the existence of overall qualitative treatment effects, especially when there are a large number of prognostic covariates. When covariates do not have qualitative treatment effects, the optimal treatment regime will assign the same treatment to all patients regardless of their covariate values. In this article, we consider testing the overall qualitative treatment effects of patients’ prognostic covariates in a high-dimensional setting. We propose a sample splitting method to construct the test statistic, based on a nonparametric estimator of the contrast function. When the dimension of covariates is large, we construct the test based on sparse random projections of covariates into a low-dimensional space. We prove the consistency of our test statistic. In the regular cases, we show the asymptotic power function of our test statistic is asymptotically the same as the “oracle” test statistic which is constructed based on the “optimal” projection matrix. Simulation studies and real data applications validate our theoretical findings. Supplementary materials for this article are available online.

Precision medicine is an emerging medical paradigm that focuses on finding the most effective treatment strategy tailored for individual patients. In the literature, most of the existing works focused on estimating the optimal treatment regime. However, there has been less attention devoted to hypothesis testing regarding the optimal treatment regime. In this paper, we first introduce the notion of conditional qualitative treatment effects (CQTE) of a set of variables given another set of variables and provide a class of equivalent representations for the null hypothesis of no CQTE. The proposed definition of CQTE does not assume any parametric form for the optimal treatment rule and plays an important role for assessing the incremental value of a set of new variables in optimal treatment decision making conditional on an existing set of prescriptive variables. We then propose novel testing procedures for no CQTE based on kernel estimation of the conditional contrast functions. We show that our test statistics have asymptotically correct size and nonnegligible power against some nonstandard local alternatives. The empirical performance of the proposed tests are evaluated by simulations and an application to an AIDS data set.

Statistical relational learning is primarily concerned with learning and inferring relationships between entities in large-scale knowledge graphs. Nickel et al. (2011) proposed a RESCAL tensor factorization model for statistical relational learning, which achieves better or at least comparable results on common benchmark data sets when compared to other state-of-the-art methods. Given a positive integer s, RESCAL computes an s-dimensional latent vector for each entity. The latent factors can be further used for solving relational learning tasks, such as collective classification, collective entity resolution and link-based clustering. The focus of this paper is to determine the number of latent factors in the RESCAL model. Due to the structure of the RESCAL model, its log-likelihood function is not concave. As a result, the corresponding maximum likelihood estimators (MLEs) may not be consistent. Nonetheless, we design a specific pseudometric, prove the consistency of the MLEs under this pseudometric and establish its rate of convergence. Based on these results, we propose a general class of information criteria and prove their model selection consistencies when the number of relations is either bounded or diverges at a proper rate of the number of entities. Simulations and real data examples show that our proposed information criteria have good finite sample properties.

The divide and conquer method is a common strategy for handling massive data. In this article, we study the divide and conquer method for cubic-rate estimators under the massive data framework. We develop a general theory for establishing the asymptotic distribution of the aggregated M-estimators using a weighted average with weights depending on the subgroup sample sizes. Under certain condition on the growing rate of the number of subgroups, the resulting aggregated estimators are shown to have faster convergence rate and asymptotic normal distribution, which are more tractable in both computation and inference than the original M-estimators based on pooled data. Our theory applies to a wide class of M-estimators with cube root convergence rate, including the location estimator, maximum score estimator, and value search estimator. Empirical performance via simulations and a real data application also validate our theoretical findings. Supplementary materials for this article are available online.

Precision medicine is a medical paradigm that focuses on finding the most effective treatment decision based on individual patient information. For many complex diseases, such as cancer, treatment decisions need to be tailored over time according to patients’ responses to previous treatments. Such an adaptive strategy is referred as a dynamic treatment regime. A major challenge in deriving an optimal dynamic treatment regime arises when an extraordinary large number of prognostic factors, such as patient’s genetic information, demographic characteristics, medical history and clinical measurements over time are available, but not all of them are necessary for making treatment decision. This makes variable selection an emerging need in precision medicine. In this paper, we propose a penalized multi-stage $A$-learning for deriving the optimal dynamic treatment regime when the number of covariates is of the nonpolynomial (NP) order of the sample size. To preserve the double robustness property of the $A$-learning method, we adopt the Dantzig selector, which directly penalizes the A-leaning estimating equations. Oracle inequalities of the proposed estimators for the parameters in the optimal dynamic treatment regime and error bounds on the difference between the value functions of the estimated optimal dynamic treatment regime and the true optimal dynamic treatment regime are established. Empirical performance of the proposed approach is evaluated by simulations and illustrated with an application to data from the STAR∗D study.

In order to identify important variables that are involved in making optimal treatment decision, Lu, Zhang and Zeng (2013) proposed a penalized least squared regression framework for a fixed number of predictors, which is robust against the misspecification of the conditional mean model. Two problems arise: (i) in a world of explosively big data, effective methods are needed to handle ultra-high dimensional data set, for example, with the dimension of predictors is of the non-polynomial (NP) order of the sample size; (ii) both the propensity score and conditional mean models need to be estimated from data under NP dimensionality. In this paper, we propose a robust procedure for estimating the optimal treatment regime under NP dimensionality. In both steps, penalized regressions are employed with the non-concave penalty function, where the conditional mean model of the response given predictors may be misspecified. The asymptotic properties, such as weak oracle properties, selection consistency and oracle distributions, of the proposed estimators are investigated. In addition, we study the limiting distribution of the estimated value function for the obtained optimal treatment regime. The empirical performance of the proposed estimation method is evaluated by simulations and an application to a depression dataset from the STAR∗D study.