A full parametric and linear specification may be insufficient to capture complicated patterns in studies exploring complex features, such as those investigating age-related changes in brain functional abilities. Alternatively, a partially linear model (PLM) consisting of both parametric and non-parametric elements may have a better fit. This model has been widely applied in economics, environmental science, and biomedical studies. In this paper, we introduce a novel statistical inference framework that equips PLM with high estimation efficiency by effectively synthesizing summary information from external data into the main analysis. Such an integrative scheme is versatile in assimilating various types of reduced models from the external study. The proposed method is shown to be theoretically valid and numerically convenient, and it ensures a high-efficiency gain compared to classic methods in PLM. Our method is further validated using two data applications by evaluating the risk factors of brain imaging measures and blood pressure.
Transportable inference using target population summary statistics under covariate shift
Academy of Mathematics and Systems Science Chinese Academy of Sciences（中国科学院数学与系统科学研究院）；Department of Biostatistics Mailman School of Public Health Columbia University（哥伦比亚大学麦尔曼公共卫生学院生物统计学系）；Department of Epidemiology & Biostatistics University of California at San Francisco（旧金山大学生物统计与流行病学系）
Identifying informative predictors in a high dimensional regression model is a critical step for association analysis and predictive modeling. Signal detection in the high dimensional setting often fails due to the limited sample size. One approach to improve power is through meta-analyzing multiple studies on the same scientific question. However, integrative analysis of high dimensional data from multiple studies is challenging in the presence of between study heterogeneity. The challenge is even more pronounced with additional data sharing constraints under which only summary data but not i…
Integrative analysis of datasets generated by multiple cohorts is a widely-used approach for increasing sample size, precision of population estimators, and generalizability of analysis results in epidemiological studies. However, often each individual cohort dataset does not have all variables of interest for an integrative analysis collected as a part of an original study. Such cohort-level missingness poses methodological challenges to the integrative analysis since missing variables have traditionally: (1) been removed from the data for complete case analysis; or (2) been completed by miss…
When data on treatment assignment, outcomes, and covariates from a randomized trial are available, a question of interest is to what extent covariates can be used to optimize treatment decisions. Statistical hypothesis testing of covariate-by-treatment interaction is ill-suited for this purpose. The application of decision theory results in treatment rules that compare the expected benefit of treatment given the patient's covariates against a treatment threshold. However, determining treatment threshold is often context-specific, and any given threshold might seem arbitrary when the overall ca…
Although there is a rapidly growing literature on dynamic connectivity methods, the primary focus has been on separate network estimation for each individual, which fails to leverage common patterns of information. We propose novel graph-theoretic approaches for estimating a population of dynamic networks that are able to borrow information across multiple heterogeneous samples in an unsupervised manner and guided by covariate information. Specifically, we develop a Bayesian product mixture model that imposes independent mixture priors at each time scan and uses covariates to model the mixture…
For data with high-dimensional covariates but small to moderate sample sizes, the analysis of single datasets often generates unsatisfactory results. The integrative analysis of multiple independent datasets provides an effective way of pooling information and outperforms single-dataset analysis and some alternative multi-datasets approaches including meta-analysis. Under certain scenarios, multiple datasets are expected to share common important covariates, that is, the multiple models have similarity in sparsity structures. However, the existing methods do not have a mechanism to {\it promot…
The focus of this paper is on quantifying the capacity of covariates in devising efficient treatment rules when data from a randomized trial are available. Conventional one-variable-at-a-time subgroup analysis based on statistical hypothesis testing of covariate-by-treatment interaction is ill-suited for this purpose. The application of decision theory results in treatment rules that compare the expected benefit of treatment given the patient's covariates against a treatment threshold. However, determining treatment threshold is often context-specific, and any given threshold might seem arbitr…
We propose a method for summarizing the strength of association between a set of variables and a multivariate outcome. Classical summary measures are appropriate when linear relationships exist between covariates and outcomes, while our approach provides an alternative that is useful in situations where complex relationships may be present. We utilize ensemble machine learning to detect nonlinear relationships and covariate interactions and propose a measure of association that captures these relationships. A hypothesis test about the proposed associative measure can be used to test the strong…
In many biomedical problems, data are often heterogeneous, with samples spanning multiple patient subgroups, where different subgroups may have different disease subtypes, stages, or other medical contexts. These subgroups may be related, but they are also expected to have differences with respect to the underlying biology. The heterogeneous data presents a precious opportunity to explore the heterogeneities and commonalities between related subgroups. Unfortunately, effective statistical analysis methods are still lacking. Recently, several novel methods based on integrative analysis have bee…
An important problem in network analysis is predicting a node attribute using both network covariates, such as graph embedding coordinates or local subgraph counts, and conventional node covariates, such as demographic characteristics. While standard regression methods that make use of both types of covariates may be used for prediction, statistical inference is complicated by the fact that the nodal summary statistics are often dependent in complex ways. We show that under a mild joint exchangeability assumption, a network analog of conformal prediction achieves finite sample validity for a w…
For survival data with high-dimensional covariates, results generated in the analysis of a single dataset are often unsatisfactory because of the small sample size. Integrative analysis pools raw data from multiple independent studies with comparable designs, effectively increases sample size, and has better performance than meta-analysis and single-dataset analysis. In this study, we conduct integrative analysis of survival data under the accelerated failure time (AFT) model. The sparsity structures of multiple datasets are described using the homogeneity and heterogeneity models. For variabl…
In this paper, we focus on estimating the average treatment effect (ATE) of a target population when individual-level data from a source population and summary-level data (e.g., first or second moments of certain covariates) from the target population are available. In the presence of heterogeneous treatment effect, the ATE of the target population can be different from that of the source population when distributions of treatment effect modifiers are dissimilar in these two populations, a phenomenon also known as covariate shift. Many methods have been developed to adjust for covariate shift,…
Receiver operating characteristic (ROC) analysis is one of the most popular approaches for evaluating and comparing the accuracy of medical diagnostic tests. Although various methodologies have been developed for estimating ROC curves and its associated summary indices, there is no consensus on a single framework that can provide consistent statistical inference whilst handling the complexities associated with medical data. Such complexities might include covariates that influence the diagnostic potential of a test, ordinal test data, censored data due to instrument detection limits or correla…
Evidence-based decision making often relies on meta-analyzing multiple studies, which enables more precise estimation and investigation of generalizability. Integrative analysis of multiple heterogeneous studies is, however, highly challenging in the ultra high dimensional setting. The challenge is even more pronounced when the individual level data cannot be shared across studies, known as DataSHIELD constraint (Wolfson et al., 2010). Under sparse regression models that are assumed to be similar yet not identical across studies, we propose in this paper a novel integrative estimation procedur…
Cardiovascular diseases (CVD), including atherosclerosis CVD (ASCVD), are multifactorial diseases that present a major economic and social burden worldwide. Tremendous efforts have been made to understand traditional risk factors for ASCVD, but these risk factors account for only about half of all cases of ASCVD. It remains a critical need to identify nontraditional risk factors (e.g., genetic variants, genes) contributing to ASCVD. Further, incorporating functional knowledge in prediction models have the potential to reveal pathways associated with disease risk. We propose Bayesian hierarchic…
Integrating the summary statistics from genome-wide association study (\textsc{gwas}) and expression quantitative trait loci (e\textsc{qtl}) data provides a powerful way of identifying the genes whose expression levels are potentially associated with complex diseases. A parameter called $T$-score that quantifies the genetic overlap between a gene and the disease phenotype based on the summary statistics is introduced based on the mean values of two Gaussian sequences. Specifically, given two independent samples $\mathbf{x}_n\sim N(θ, Σ_1)$ and $\mathbf{y}_n\sim N(μ, Σ_2)$, the $T$-score is def…
Genetic risk prediction is an important component of individualized medicine, but prediction accuracies remain low for many complex diseases. A fundamental limitation is the sample sizes of the studies on which the prediction algorithms are trained. One way to increase the effective sample size is to integrate information from previously existing studies. However, it can be difficult to find existing data that examine the target disease of interest, especially if that disease is rare or poorly studied. Furthermore, individual-level genotype data from these auxiliary studies are typically diffi…
Spatial ecological networks are widely used to model interactions between georeferenced biological entities (e.g., populations or communities). The analysis of such data often leads to a two-step approach where groups containing similar biological entities are firstly identified and the spatial information is used afterwards to improve the ecological interpretation. We develop an integrative approach to retrieve groups of nodes that are geographically close and ecologically similar. Our model-based spatially-constrained method embeds the geographical information within a regularization framewo…
It is becoming increasingly common for researchers to consider incorporating external information from large studies to improve the accuracy of statistical inference instead of relying on a modestly sized dataset collected internally. With some new predictors only available internally, we aim to build improved regression models based on individual-level data from an "internal" study while incorporating summary-level information from "external" models. We propose a meta-analysis framework along with two weighted estimators as the composite of empirical Bayes estimators, which combines the estim…
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…
In modern biomedical research, it is ubiquitous to have multiple data sets measured on the same set of samples from different views (i.e., multi-view data). For example, in genetic studies, multiple genomic data sets at different molecular levels or from different cell types are measured for a common set of individuals to investigate genetic regulation. Integration and reduction of multi-view data have the potential to leverage information in different data sets, and to reduce the magnitude and complexity of data for further statistical analysis and interpretation. In this paper, we develop a …
Motivated by the need to study the molecular mechanism underlying Type 1 Diabetes (T1D) with the gene expression data collected from both the patients and healthy controls at multiple time points, we propose an innovative method for jointly estimating multiple dependent Gaussian graphical models. Compared to the existing methods, the proposed method has a few significant advantages. First, it includes a meta-analysis procedure to explicitly integrate information across distinct conditions. In contrast, the existing methods often integrate information through prior distributions or penalty func…
Motivation: Genome-wide association studies (GWASs), which assay more than a million single nucleotide polymorphisms (SNPs) in thousands of individuals, have been widely used to identify genetic risk variants for complex diseases. However, most of the variants that have been identified contribute relatively small increments of risk and only explain a small portion of the genetic variation in complex diseases. This is the so-called missing heritability problem. Evidence has indicated that many complex diseases are genetically related, meaning these diseases share common genetic risk variants. T…
In many environmental applications involving spatially-referenced data, limitations on the number and locations of observations motivate the need for practical and efficient models for spatial interpolation, or kriging. A key component of models for continuously-indexed spatial data is the covariance function, which is traditionally assumed to belong to a parametric class of stationary models. While convenient, the assumption of stationarity is rarely realistic; as a result, there is a rich literature on alternative methodologies which capture and model the nonstationarity present in most envi…
We introduce the transport-transform (TT) and the relative transport-transform (RTT) metrics between finite point patterns on a general space, which provide a unified framework for earlier point pattern metrics, in particular the generalized spike time and the normalized and unnormalized OSPA metrics. Our main focus is on barycenters, i.e. minimizers of a $q$-th order Fréchet functional with respect to these metrics. We present a heuristic algorithm that terminates in a local minimum and is shown to be fast and reliable in a simulation study. The algorithm serves as an umbrella method that can…
BACKGROUND There is an increasing demand for high quality subnational estimates of under-five mortality. In low and middle income countries, where the burden of under-five mortality is concentrated, vital registration is often lacking and household surveys, which provide full birth history data, are often the most reliable source. Unfortunately, these data are spatially sparse and so data are pulled from other sources to increase the available information. Summary birth histories represent a large fraction of the available data, and provide numbers of births and deaths aggregated over time, al…
Propensity score analysis with latent covariates: Measurement error bias correction using the covariate's posterior mean, aka the inclusive factor score
Johns Hopkins Bloomberg School of Public Health（约翰斯·霍普金斯大学彭博公共卫生学院）
A large number of recent genome-wide association studies (GWASs) for complex phenotypes confirm the early conjecture for polygenicity, suggesting the presence of large number of variants with only tiny or moderate effects. However, due to the limited sample size of a single GWAS, many associated genetic variants are too weak to achieve the genome-wide significance. These undiscovered variants further limit the prediction capability of GWAS. Restricted access to the individual-level data and the increasing availability of the published GWAS results motivate the development of methods integratin…
