One important problem in genome science is to determine sets of co-regulated genes based on measurements of gene expression levels across samples, where the quantification of expression levels includes substantial technical and biological noise. To address this problem, we developed a Bayesian sparse latent factor model that uses a three parameter beta prior to flexibly model shrinkage in the loading matrix. By applying three layers of shrinkage to the loading matrix (global, factor-specific, and element-wise), this model has non-parametric properties in that it estimates the appropriate number of factors from the data. We added a two-component mixture to model each factor loading as being generated from either a sparse or a dense mixture component; this allows dense factors that capture confounding noise, and sparse factors that capture local gene interactions. We developed two statistics to quantify the stability of the recovered matrices for both sparse and dense matrices. We tested our model on simulated data and found that we successfully recovered the true latent structure as compared to related models. We applied our model to a large gene expression study and found that we recovered known covariates and small groups of co-regulated genes. We validated these gene subsets by testing for associations between genotype data and these latent factors, and we found a substantial number of biologically important genetic regulators for the recovered gene subsets.
We develop Bayesian nonparametric models for spatially indexed data of mixed type. Our work is motivated by challenges that occur in environmental epidemiology, where the usual presence of several confounding variables that exhibit complex interactions and high correlations makes it difficult to estimate and understand the effects of risk factors on health outcomes of interest. The modeling approach we adopt assumes that responses and confounding variables are manifestations of continuous latent variables, and uses multivariate Gaussians to jointly model these. Responses and confounding variab…
Bayesian causal inference offers a principled approach to policy evaluation of proposed interventions on mediators or time-varying exposures. We outline a general approach to the estimation of causal quantities for settings with time-varying confounding, such as exposure-induced mediator-outcome confounders. We further extend this approach to propose two Bayesian data fusion (BDF) methods for unmeasured confounding. Using informative priors on quantities relating to the confounding bias parameters, our methods incorporate data from an external source where the confounder is measured in order t…
In brain oncology, it is routine to evaluate the progress or remission of the disease based on the differences between a pre-treatment and a post-treatment Positron Emission Tomography (PET) scan. Background adjustment is necessary to reduce confounding by tissue-dependent changes not related to the disease. When modeling the voxel intensities for the two scans as a bivariate Gaussian mixture, background adjustment translates into standardizing the mixture at each voxel, while tumor lesions present themselves as outliers to be detected. In this paper, we address the question of how to standard…
Regularized regression models are well studied and, under appropriate conditions, offer fast and statistically interpretable results. However, large data in many applications are heterogeneous in the sense of harboring distributional differences between latent groups. Then, the assumption that the conditional distribution of response Y given features X is the same for all samples may not hold. Furthermore, in scientific applications, the covariance structure of the features may contain important signals and its learning is also affected by latent group structure. We propose a class of mixture …
Rochester Institute of Technology（罗切斯特理工学院）；Dalhousie University（达尔豪斯大学）
While deep representation learning has become increasingly capable of separating task-relevant representations from other confounding factors in the data, two significant challenges remain. First, there is often an unknown and potentially infinite number of confounding factors coinciding in the data. Second, not all of these factors are readily observable. In this paper, we present a deep conditional generative model that learns to disentangle a task-relevant representation from an unknown number of confounding factors that may grow infinitely. This is achieved by marrying the representational…
Non-gaussian spatial data are very common in many disciplines. For instance, count data are common in disease mapping, and binary data are common in ecology. When fitting spatial regressions for such data, one needs to account for dependence to ensure reliable inference for the regression coefficients. The spatial generalized linear mixed model (SGLMM) offers a very popular and flexible approach to modeling such data, but the SGLMM suffers from three major shortcomings: (1) uninterpretability of parameters due to spatial confounding, (2) variance inflation due to spatial confounding, and (3) h…
When computer codes are used for modeling complex physical systems, their unknown parameters are tuned by calibration techniques. A discrepancy function may be added to the computer code in order to capture its discrepancy with the real physical process. By considering the validation question of a computer code as a Bayesian selection model problem, Damblin et al. (2016) have highlighted a possible confounding effect in certain configurations between the code discrepancy and a linear computer code by using a Bayesian testing procedure based on the intrinsic Bayes factor. In this paper, we inve…
It is generally acknowledged that most complex diseases are affected in part by interactions between genes and genes and/or between genes and environmental factors. Taking into account environmental exposures and their interactions with genetic factors in genome-wide association studies (GWAS) can help to identify high-risk subgroups in the population and provide a better understanding of the disease. For this reason, many methods have been developed to detect gene-environment (G*E) interactions. Despite this, few loci that interact with environmental exposures have been identified so far. Ind…
Clinical machine learning applications are often plagued with confounders that can impact the generalizability and predictive performance of the learners. Confounding is especially problematic in remote digital health studies where the participants self-select to enter the study, thereby making it challenging to balance the demographic characteristics of participants. One effective approach to combat confounding is to match samples with respect to the confounding variables in order to balance the data. This procedure, however, leads to smaller datasets and hence impact the inferences drawn fro…
Background: There is increasing interest in approaches for analyzing the effect of exposure mixtures on health. A key issue is how to simultaneously analyze often highly collinear components of the mixture, which can create problems such as confounding by co-exposure and co-exposure amplification bias (CAB). Evaluation of novel mixtures methods, typically using synthetic data, is critical to their ultimate utility. Objectives: This paper aims to answer two questions. How do causal models inform the interpretation of statistical models and the creation of synthetic data used to test them? Are n…
Spatial confounding is how is called the confounding between fixed and spatial random effects. It has been widely studied and it gained attention in the past years in the spatial statistics literature, as it may generate unexpected results in modeling. The projection-based approach, also known as restricted models, appears as a good alternative to overcome the spatial confounding in generalized linear mixed models. However, when the support of fixed effects is different from the spatial effect one, this approach can no longer be applied directly. In this work, we introduce a method to alleviat…
There has been great interest recently in applying nonparametric kernel mixtures in a hierarchical manner to model multiple related data samples jointly. In such settings several data features are commonly present: (i) the related samples often share some, if not all, of the mixture components but with differing weights, (ii) only some, not all, of the mixture components vary across the samples, and (iii) often the shared mixture components across samples are not aligned perfectly in terms of their location and spread, but rather display small misalignments either due to systematic cross-sampl…
No unmeasured confounding is often assumed in estimating treatment effects in observational data when using approaches such as propensity scores and inverse probability weighting. However, in many such studies due to the limitation of the databases, collected confounders are not exhaustive, and it is crucial to examine the extent to which the resulting estimate is sensitive to the unmeasured confounders. We consider this problem for survival and competing risks data. Due to the complexity of models for such data, we adapt the simulated potential confounders approach of Carnegie et al. (2016), …
Standardization, a common approach for controlling confounding in population-studies or data from disease registries, is defined to be a weighted average of stratum specific rates. Typically, discussions on the construction of a particular standardized rate regard the strata as fixed, and focus on the considerations that affect the specification of weights. Each year the data from the SEER cancer registries are analyzed using a weighting procedure referred to as ``direct standardization for age.'' To evaluate the performance of direct standardization, we define a general class of standardizati…
In causal mediation studies that decompose an average treatment effect into a natural indirect effect (NIE) and a natural direct effect (NDE), examples of post-treatment confounding are abundant. Past research has generally considered it infeasible to adjust for a post-treatment confounder of the mediator-outcome relationship due to incomplete information: it is observed under the actual treatment condition while missing under the counterfactual treatment condition. This study proposes a new sensitivity analysis strategy for handling post-treatment confounding and incorporates it into weightin…
Recently, Saeb et al (2017) showed that, in diagnostic machine learning applications, having data of each subject randomly assigned to both training and test sets (record-wise data split) can lead to massive underestimation of the cross-validation prediction error, due to the presence of "subject identity confounding" caused by the classifier's ability to identify subjects, instead of recognizing disease. To solve this problem, the authors recommended the random assignment of the data of each subject to either the training or the test set (subject-wise data split). The adoption of subject-wise…
Calculating the Expected Value of Sample Information for Observational Studies affected by Confounding
Human Technopole（人类技术中心）；Department of Statistical Science, University College London（伦敦大学学院统计科学系）；The Hospital for Sick Children（多伦多儿童医院）；University of Toronto（多伦多大学）
