Mendelian randomization is a widely-used method to estimate the unconfounded effect of an exposure on an outcome by using genetic variants as instrumental variables. Mendelian randomization analyses which use variants from a single genetic region (cis-MR) have gained popularity for being an economical way to provide supporting evidence for drug target validation. This paper proposes methods for cis-MR inference which use the explanatory power of many correlated variants to make valid inferences even in situations where those variants only have weak effects on the exposure. In particular, we exploit the highly structured nature of genetic correlations in single gene regions to reduce the dimension of genetic variants using factor analysis. These genetic factors are then used as instrumental variables to construct tests for the causal effect of interest. Since these factors may often be weakly associated with the exposure, size distortions of standard t-tests can be severe. Therefore, we consider two approaches based on conditional testing. First, we extend results of commonly-used identification-robust tests to account for the use of estimated factors as instruments. Secondly, we propose a test which appropriately adjusts for first-stage screening of genetic factors based on their relevance. Our empirical results provide genetic evidence to validate cholesterol-lowering drug targets aimed at preventing coronary heart disease.
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Anomaly detection among a large number of processes arises in many applications ranging from dynamic spectrum access to cybersecurity. In such problems one can often obtain noisy observations aggregated from a chosen subset of processes that conforms to a tree structure. The distribution of these observations, based on which the presence of anomalies is detected, may be only partially known. This gives rise to the need for a search strategy designed to account for both the sample complexity and the detection accuracy, as well as cope with statistical models that are known only up to some missing parameters. In this work we propose a sequential search strategy using two variations of the Generalized Local Likelihood Ratio statistic. Our proposed Hierarchical Dynamic Search (HDS) strategy is shown to be order-optimal with respect to the size of the search space and asymptotically optimal with respect to the detection accuracy. An explicit upper bound on the error probability of HDS is established for the finite sample regime. Extensive experiments are conducted, demonstrating the performance gains of HDS over existing methods.
Data collection and research methodology represents a critical part of the research pipeline. On the one hand, it is important that we collect data in a way that maximises the validity of what we are measuring, which may involve the use of long scales with many items. On the other hand, collecting a large number of items across multiple scales results in participant fatigue, and expensive and time consuming data collection. It is therefore important that we use the available resources optimally. In this work, we consider how a consideration for theory and the associated causal/structural model can help us to streamline data collection procedures by not wasting time collecting data for variables which are not causally critical for subsequent analysis. This not only saves time and enables us to redirect resources to attend to other variables which are more important, but also increases research transparency and the reliability of theory testing. In order to achieve this streamlined data collection, we leverage structural models, and Markov conditional independency structures implicit in these models to identify the substructures which are critical for answering a particular research question. In this work, we review the relevant concepts and present a number of didactic examples with the hope that psychologists can use these techniques to streamline their data collection process without invalidating the subsequent analysis. We provide a number of simulation results to demonstrate the limited analytical impact of this streamlining.
Numerical solution of heterogeneous Helmholtz problems presents various computational challenges, with descriptive theory remaining out of reach for many popular approaches. Robustness and scalability are key for practical and reliable solvers in large-scale applications, especially for large wave number problems. In this work we explore the use of a GenEO-type coarse space to build a two-level additive Schwarz method applicable to highly indefinite Helmholtz problems. Through a range of numerical tests on a 2D model problem, discretised by finite elements on pollution-free meshes, we observe robust convergence, iteration counts that do not increase with the wave number, and good scalability of our approach. We further provide results showing a favourable comparison with the DtN coarse space. Our numerical study shows promise that our solver methodology can be effective for challenging heterogeneous applications.
Randomized field experiments are the gold standard for evaluating the impact of software changes on customers. In the online domain, randomization has been the main tool to ensure exchangeability. However, due to the different deployment conditions and the high dependence on the surrounding environment, designing experiments for automotive software needs to consider a higher number of restricted variables to ensure conditional exchangeability. In this paper, we show how at Volvo Cars we utilize causal graphical models to design experiments and explicitly communicate the assumptions of experiments. These graphical models are used to further assess the experiment validity, compute direct and indirect causal effects, and reason on the transportability of the causal conclusions.
This paper considers the problem of inference in cluster randomized experiments when cluster sizes are non-ignorable. Here, by a cluster randomized experiment, we mean one in which treatment is assigned at the level of the cluster; by non-ignorable cluster sizes we mean that "large" clusters and "small" clusters may be heterogeneous, and, in particular, the effects of the treatment may vary across clusters of differing sizes. In order to permit this sort of flexibility, we consider a sampling framework in which cluster sizes themselves are random. In this way, our analysis departs from earlier analyses of cluster randomized experiments in which cluster sizes are treated as non-random. We distinguish between two different parameters of interest: the equally-weighted cluster-level average treatment effect, and the size-weighted cluster-level average treatment effect. For each parameter, we provide methods for inference in an asymptotic framework where the number of clusters tends to infinity and treatment is assigned using simple random sampling. We additionally permit the experimenter to sample only a subset of the units within each cluster rather than the entire cluster and demonstrate the implications of such sampling for some commonly used estimators. A small simulation study shows the practical relevance of our theoretical results.
Multi-scale problems, where variables of interest evolve in different time-scales and live in different state-spaces. can be found in many fields of science. Here, we introduce a new recursive methodology for Bayesian inference that aims at estimating the static parameters and tracking the dynamic variables of these kind of systems. Although the proposed approach works in rather general multi-scale systems, for clarity we analyze the case of a heterogeneous multi-scale model with 3 time-scales (static parameters, slow dynamic state variables and fast dynamic state variables). The proposed scheme, based on nested filtering methodology of P\'erez-Vieites et al. (2018), combines three intertwined layers of filtering techniques that approximate recursively the joint posterior probability distribution of the parameters and both sets of dynamic state variables given a sequence of partial and noisy observations. We explore the use of sequential Monte Carlo schemes in the first and second layers while we use an unscented Kalman filter to obtain a Gaussian approximation of the posterior probability distribution of the fast variables in the third layer. Some numerical results are presented for a stochastic two-scale Lorenz 96 model with unknown parameters.
In randomized experiments, the actual treatments received by some experimental units may differ from their treatment assignments. This non-compliance issue often occurs in clinical trials, social experiments, and the applications of randomized experiments in many other fields. Under certain assumptions, the average treatment effect for the compliers is identifiable and equal to the ratio of the intention-to-treat effects of the potential outcomes to that of the potential treatment received. To improve the estimation efficiency, we propose three model-assisted estimators for the complier average treatment effect in randomized experiments with a binary outcome. We study their asymptotic properties, compare their efficiencies with that of the Wald estimator, and propose the Neyman-type conservative variance estimators to facilitate valid inferences. Moreover, we extend our methods and theory to estimate the multiplicative complier average treatment effect. Our analysis is randomization-based, allowing the working models to be misspecified. Finally, we conduct simulation studies to illustrate the advantages of the model-assisted methods and apply these analysis methods in a randomized experiment to evaluate the effect of academic services or incentives on academic performance.
The numerical solution of singular eigenvalue problems is complicated by the fact that small perturbations of the coefficients may have an arbitrarily bad effect on eigenvalue accuracy. However, it has been known for a long time that such perturbations are exceptional and standard eigenvalue solvers, such as the QZ algorithm, tend to yield good accuracy despite the inevitable presence of roundoff error. Recently, Lotz and Noferini quantified this phenomenon by introducing the concept of $\delta$-weak eigenvalue condition numbers. In this work, we consider singular quadratic eigenvalue problems and two popular linearizations. Our results show that a correctly chosen linearization increases $\delta$-weak eigenvalue condition numbers only marginally, justifying the use of these linearizations in numerical solvers also in the singular case. We propose a very simple but often effective algorithm for computing well-conditioned eigenvalues of a singular quadratic eigenvalue problems by adding small random perturbations to the coefficients. We prove that the eigenvalue condition number is, with high probability, a reliable criterion for detecting and excluding spurious eigenvalues created from the singular part.
We develop methods for reducing the dimensionality of large data sets, common in biomedical applications. Learning about patients using genetic data often includes more features than observations, which makes direct supervised learning difficult. One method of reducing the feature space is to use latent Dirichlet allocation to group genetic variants in an unsupervised manner. Latent Dirichlet allocation describes a patient as a mixture of topics corresponding to genetic variants. This can be generalized as a Bayesian tensor decomposition to account for multiple feature variables. Our most significant contributions are with hierarchical topic modeling. We design distinct methods of incorporating hierarchical topic modeling, based on nested Chinese restaurant processes and Pachinko Allocation Machine, into Bayesian tensor decomposition. We apply these models to examine patients with one of four common types of cancer (breast, lung, prostate, and colorectal) and siblings with and without autism spectrum disorder. We linked the genes with their biological pathways and combine this information into a tensor of patients, counts of their genetic variants, and the genes' membership in pathways. We find that our trained models outperform baseline models, with respect to coherence, by up to 40%.
Many current applications use recommendations in order to modify the natural user behavior, such as to increase the number of sales or the time spent on a website. This results in a gap between the final recommendation objective and the classical setup where recommendation candidates are evaluated by their coherence with past user behavior, by predicting either the missing entries in the user-item matrix, or the most likely next event. To bridge this gap, we optimize a recommendation policy for the task of increasing the desired outcome versus the organic user behavior. We show this is equivalent to learning to predict recommendation outcomes under a fully random recommendation policy. To this end, we propose a new domain adaptation algorithm that learns from logged data containing outcomes from a biased recommendation policy and predicts recommendation outcomes according to random exposure. We compare our method against state-of-the-art factorization methods, in addition to new approaches of causal recommendation and show significant improvements.
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