We propose a distributed quadratic inference function framework to jointly estimate regression parameters from multiple potentially heterogeneous data sources with correlated vector outcomes. The primary goal of this joint integrative analysis is to estimate covariate effects on all outcomes through a marginal regression model in a statistically and computationally efficient way. We develop a data integration procedure for statistical estimation and inference of regression parameters that is implemented in a fully distributed and parallelized computational scheme. To overcome computational and modeling challenges arising from the high-dimensional likelihood of the correlated vector outcomes, we propose to analyze each data source using Qu, Lindsay and Li (2000)'s quadratic inference functions, and then to jointly reestimate parameters from each data source by accounting for correlation between data sources using a combined meta-estimator in a similar spirit to Hansen (1982)'s generalised method of moments. We show both theoretically and numerically that the proposed method yields efficiency improvements and is computationally fast. We illustrate the proposed methodology with the joint integrative analysis of the association between smoking and metabolites in a large multi-cohort study and provide an R package for ease of implementation.
In the genomic analysis, it is significant while challenging to identify markers associated with cancer outcomes or phenotypes. Based on the biological mechanisms of cancers and the characteristics of datasets as well, this paper proposes a novel integrative interaction approach under the semiparametric model, in which the genetic factors and environmental factors are included as the parametric and nonparametric components, respectively. The goal of this approach is to identify the genetic factors and gene-gene interactions associated with cancer outcomes, and meanwhile, estimate the nonlinear…
Multi-task learning is increasingly used to investigate the association structure between multiple responses and a single set of predictor variables in many applications. In the era of big data, the coexistence of incomplete outcomes, large number of responses, and high dimensionality in predictors poses unprecedented challenges in estimation, prediction, and computation. In this paper, we propose a scalable and computationally efficient procedure, called PEER, for large-scale multi-response regression with incomplete outcomes, where both the numbers of responses and predictors can be high-dim…
It is more and more common to explore the genome at diverse levels and not only at a single omic level. Through integrative statistical methods, omics data have the power to reveal new biological processes, potential biomarkers, and subgroups of a cohort. The matrix factorization (MF) is a unsupervised statistical method that allows giving a clustering of individuals, but also revealing relevant omic variables from the various blocks. Here, we present PIntMF (Penalized Integrative Matrix Factorization), a model of MF with sparsity, positivity and equality constraints.To induce sparsity in the …
Extensions in the field of joint modeling of correlated data and dynamic predictions improve the development of prognosis research. The R package frailtypack provides estimations of various joint models for longitudinal data and survival events. In particular, it fits models for recurrent events and a terminal event (frailtyPenal), models for two survival outcomes for clustered data (frailtyPenal), models for two types of recurrent events and a terminal event (multivPenal), models for a longitudinal biomarker and a terminal event (longiPenal) and models for a longitudinal biomarker, recurrent …
Significant advances in biotechnology have allowed for simultaneous measurement of molecular data points across multiple genomic and transcriptomic levels from a single tumor/cancer sample. This has motivated systematic approaches to integrate multi-dimensional structured datasets since cancer development and progression is driven by numerous co-ordinated molecular alterations and the interactions between them. We propose a novel two-step Bayesian approach that combines a variable selection framework with integrative structure learning between multiple sources of data. The structure learning i…
Rapid advancements in collection and dissemination of multi-platform molecular and genomics data has resulted in enormous opportunities to aggregate such data in order to understand, prevent, and treat human diseases. While significant improvements have been made in multi-omic data integration methods to discover biological markers and mechanisms underlying both prognosis and treatment, the precise cellular functions governing these complex mechanisms still need detailed and data-driven de-novo evaluations. We propose a framework called Functional Integrative Bayesian Analysis of High-dimensio…
Many observational studies and clinical trials collect various secondary outcomes that may be highly correlated with the primary endpoint. These secondary outcomes are often analyzed in secondary analyses separately from the main data analysis. However, these secondary outcomes can be used to improve the estimation precision in the main analysis. We propose a method called Multiple Information Borrowing (MinBo) that borrows information from secondary data (containing secondary outcomes and covariates) to improve the efficiency of the main analysis. The proposed method is robust against model m…
Comparison of the LASSO and Integrative LASSO with Penalty Factors (IPF-LASSO) methods for multi-omics data: Variable selection with Type I error control
The so-called gut-brain axis has stimulated extensive research on microbiomes. One focus is to assess the association between certain clinical outcomes and the relative abundances of gut microbes, which can be presented as sub-compositional data in conformity with the taxonomic hierarchy of bacteria. Motivated by a study for identifying the microbes in the gut microbiome of preterm infants that impact their later neurobehavioral outcomes, we formulate a constrained integrative multi-view regression, where the neurobehavioral scores form multivariate response, the sub-compositional microbiome d…
Considering parallel tempering and comparing post-treatment procedures in Bayesian Profile Regression Models for a survival outcome and correlated exposures
Lasso is a popular and efficient approach to simultaneous estimation and variable selection in high-dimensional regression models. In this paper, a robust LAD-lasso method for multiple outcomes is presented that addresses the challenges of non-normal outcome distributions and outlying observations. Measured covariate data from space or time, or spectral bands or genomic positions often have natural correlation structure arising from measuring distance between the covariates. The proposed multi-outcome approach includes handling of such covariate blocks by a group fusion penalty, which encourag…
With fast advancements in technologies, the collection of multiple types of measurements on a common set of subjects is becoming routine in science. Some notable examples include multimodal neuroimaging studies for the simultaneous investigation of brain structure and function, and multi-omics studies for combining genetic and genomic information. Integrative analysis of multimodal data allows scientists to interrogate new mechanistic questions. However, the data collection and generation of integrative hypotheses is outpacing available methodology for joint analysis of multimodal measurements…
In Genome-Wide Association Studies (GWAS) where multiple correlated traits have been measured on participants, a joint analysis strategy, whereby the traits are analyzed jointly, can improve statistical power over a single-trait analysis strategy. There are two questions of interest to be addressed when conducting a joint GWAS analysis with multiple traits. The first question examines whether a genetic loci is significantly associated with any of the traits being tested. The second question focuses on identifying the specific trait(s) that is associated with the genetic loci. Since existing me…
Measurement error arises through a variety of mechanisms. A rich literature exists on the bias introduced by covariate measurement error and on methods of analysis to address this bias. By comparison, less attention has been given to errors in outcome assessment and non-classical covariate measurement error. We consider an extension of the regression calibration method to settings with errors in a continuous outcome, where the errors may be correlated with prognostic covariates or with covariate measurement error. This method adjusts for the measurement error in the data and can be applied wit…
In biomedical studies it is common to collect data on multiple biomarkers during study follow-up for dynamic prediction of a time-to-event clinical outcome. The biomarkers are typically intermittently measured, missing at some event times, and may be subject to high biological variations, which cannot be readily used as time-dependent covariates in a standard time-to-event model. Moreover, they can be highly correlated if they are from in the same biological pathway. To address these issues, we propose a flexible joint model framework that models the multiple biomarkers with a shared latent re…
Finite Mixtures of Generalized Estimating Equations for Clustering Multivariate Correlated Outcomes
Faculty of Economics, Keio University（庆应义塾大学经济学部）；Research School of Finance, Actuarial Studies and Statistics, The Australian National University（澳大利亚国立大学金融、精算与统计研究学院）
Semiparametric Copula Estimation for Spatially Correlated Multivariate Mixed Outcomes: Analyzing Visual Sightings of Fin Whales from a Line Transect Survey
Tokyo University of Science（东京理科大学）；Meisei University（明海大学）；Keio University（庆应义塾大学）；Institute of Marine Research（海洋研究所）；RIKEN Center for Brain Science（理化学研究所脑科学中心）
This article develops a Bayesian approach for estimating panel quantile regression with binary outcomes in the presence of correlated random effects. We construct a working likelihood using an asymmetric Laplace (AL) error distribution and combine it with suitable prior distributions to obtain the complete joint posterior distribution. For posterior inference, we propose two Markov chain Monte Carlo (MCMC) algorithms but prefer the algorithm that exploits the blocking procedure to produce lower autocorrelation in the MCMC draws. We also explain how to use the MCMC draws to calculate the margin…
We consider the problem of how to assign treatment in a randomized experiment, in which the correlation among the outcomes is informed by a network available pre-intervention. Working within the potential outcome causal framework, we develop a class of models that posit such a correlation structure among the outcomes. Then we leverage these models to develop restricted randomization strategies for allocating treatment optimally, by minimizing the mean square error of the estimated average treatment effect. Analytical decompositions of the mean square error, due both to the model and to the ran…
We propose a class of continuous-time Markov counting processes for analyzing correlated binary data and establish a correspondence between these models and sums of exchangeable Bernoulli random variables. Our approach generalizes many previous models for correlated outcomes, admits easily interpretable parameterizations, allows different cluster sizes, and incorporates ascertainment bias in a natural way. We demonstrate several new models for dependent outcomes and provide algorithms for computing maximum likelihood estimates. We show how to incorporate cluster-specific covariates in a regres…
It has become commonplace to use complex computer models to predict outcomes in regions where data does not exist. Typically these models need to be calibrated and validated using some experimental data, which often consists of multiple correlated outcomes. In addition, some of the model parameters may be categorical in nature, such as a pointer variable to alternate models (or submodels) for some of the physics of the system. Here we present a general approach for calibration in such situations where an emulator of the computationally demanding models and a discrepancy term from the model to …
Medical studies that depend on electronic health records (EHR) data are often subject to measurement error, as the data are not collected to support research questions under study. These data errors, if not accounted for in study analyses, can obscure or cause spurious associations between patient exposures and disease risk. Methodology to address covariate measurement error has been well developed; however, time-to-event error has also been shown to cause significant bias but methods to address it are relatively underdeveloped. More generally, it is possible to observe errors in both the cova…
Studies of Alzheimer's disease (AD) often collect multiple longitudinal clinical outcomes, which are correlated and predictive of AD progression. It is of great scientific interest to investigate the association between the outcomes and time to AD onset. We model the multiple longitudinal outcomes as multivariate sparse functional data and propose a functional joint model linking multivariate functional data to event time data. In particular, we propose a multivariate functional mixed model (MFMM) to identify the shared progression pattern and outcome-specific progression patterns of the outco…
Principal component analysis (PCA) is a well-established tool in machine learning and data processing. The principal axes in PCA were shown to be equivalent to the maximum marginal likelihood estimator of the factor loading matrix in a latent factor model for the observed data, assuming that the latent factors are independently distributed as standard normal distributions. However, the independence assumption may be unrealistic for many scenarios such as modeling multiple time series, spatial processes, and functional data, where the outcomes are correlated. In this paper, we introduce the gen…
Intraclass correlation in bilateral data has been investigated in recent decades with various statistical methods. In practice, stratifying bilateral data by some control variables will provide more sophisticated statistical results to satisfy different research proposed in random clinical trials. In this article, we propose three test statistics (likelihood ratio test, score test, and Wald-type test statistics) to evaluate the homogeneity of proportion ratios for stratified bilateral correlated data under an equal correlation assumption. Monte Carlo simulations of Type I error and power are p…
Understanding of the pathophysiology of obstructive lung disease (OLD) is limited by available methods to examine the relationship between multi-omic molecular phenomena and clinical outcomes. Integrative factorization methods for multi-omic data can reveal latent patterns of variation describing important biological signal. However, most methods do not provide a framework for inference on the estimated factorization, simultaneously predict important disease phenotypes or clinical outcomes, nor accommodate multiple imputation. To address these gaps, we propose Bayesian Simultaneous Factorizati…
Confidence interval (CI) methods for stratified bilateral studies use intraclass correlation to avoid misleading results. In this article, we propose four CI methods (sample-size weighted global MLE-based Wald-type CI, complete MLE-based Wald-type CI, profile likelihood CI, and complete MLE-based score CI) to investigate CIs of proportion ratios to clinical trial design with stratified bilateral data under Dallal's intraclass model. Monte Carlo simulations are performed, and the complete MLE-based score confidence interval (CS) method yields a robust outcome. Lastly, a real data example is con…
Value-added models have been widely used to assess the contributions of individual teachers and schools to students' academic growth based on longitudinal student achievement outcomes. There is concern, however, that ignoring the presence of missing values, which are common in longitudinal studies, can bias teachers' value-added scores. In this article, a flexible correlated random effects model is developed that jointly models the student responses and the student missing data indicators. Both the student responses and the missing data mechanism depend on latent teacher effects as well as lat…
Measuring the causal impact of an advertising campaign on sales is an essential task for advertising companies. Challenges arise when companies run advertising campaigns in multiple stores which are spatially correlated, and when the sales data have a low signal-to-noise ratio which makes the advertising effects hard to detect. This paper proposes a solution to address both of these challenges. A novel Bayesian method is proposed to detect weaker impacts and a multivariate structural time series model is used to capture the spatial correlation between stores through placing a $\mathcal{G}$-Wis…
Clinical prediction models (CPMs) are used to predict clinically relevant outcomes or events. Typically, prognostic CPMs are derived to predict the risk of a single future outcome. However, with rising emphasis on the prediction of multi-morbidity, there is growing need for CPMs to simultaneously predict risks for each of multiple future outcomes. A common approach to multi-outcome risk prediction is to derive a CPM for each outcome separately, then multiply the predicted risks. This approach is only valid if the outcomes are conditionally independent given the covariates, and it fails to expl…
IMPORTANCE: Feature selection with respect to time-to-event outcomes is one of the fundamental problems in clinical trials and biomarker discovery studies. But it's unclear which statistical methods should be used when sample size is small or some of the key covariates are not measured. DESIGN: In this simulation study, the true models are multivariate Cox proportional hazards models with 10 covariates. It's assumed that only 5 out the 10 true features are observed/measured for all model fitting, along with 5 random noise features. Each sample size scenario is explored using 10,000 simulation …
With the increasing adoption of electronic health records, there is an increasing interest in developing individualized treatment rules, which recommend treatments according to patients' characteristics, from large observational data. However, there is a lack of valid inference procedures for such rules developed from this type of data in the presence of high-dimensional covariates. In this work, we develop a penalized doubly robust method to estimate the optimal individualized treatment rule from high-dimensional data. We propose a split-and-pooled de-correlated score to construct hypothesis …
A Time-Series Model for Areal Data Using Area-Specific Gaussian Processes with Spatially Correlated Hyperparameters
KU Leuven（荷语鲁汶大学）；Hasselt University（哈瑟尔特大学）；Clinton Health Access Initiative（克林顿健康准入倡议组织）；National Malaria Control Program, Ministry of Health（卫生部国家疟疾控制项目）；University of Birmingham（伯明翰大学）
Testing effect size homogeneity is an essential part when conducting a meta-analysis. Comparative studies of effect size homogeneity tests in case of binary outcomes are found in the literature, but no test has come out as an absolute winner. A alternative approach would be to carry out multiple effect size homogeneity tests on the same meta-analysis and combine the resulting dependent p-values. In this article we applied the correlated Lancaster method for dependent statistical tests. To investigate the proposed approach's performance, we applied eight different effect size homogeneity tests …
Measurements are generally collected as unilateral or bilateral data in clinical trials or observational studies. For example, in ophthalmology studies, the primary outcome is often obtained from one eye or both eyes of an individual. In medical studies, the relative risk is usually the parameter of interest and is commonly used. In this article, we develop three confidence intervals for the relative risk for combined unilateral and bilateral correlated data under the equal dependence assumption. The proposed confidence intervals are based on maximum likelihood estimates of parameters derived …
