Many practical studies rely on hypothesis testing procedures applied to data sets with missing information. An important part of the analysis is to determine the impact of the missing data on the performance of the test, and this can be done by properly quantifying the relative (to complete data) amount of available information. The problem is directly motivated by applications to studies, such as linkage analyses and haplotype-based association projects, designed to identify genetic contributions to complex diseases. In the genetic studies the relative information measures are needed for the experimental design, technology comparison, interpretation of the data, and for understanding the behavior of some of the inference tools. The central difficulties in constructing such information measures arise from the multiple, and sometimes conflicting, aims in practice. For large samples, we show that a satisfactory, likelihood-based general solution exists by using appropriate forms of the relative Kullback--Leibler information, and that the proposed measures are computationally inexpensive given the maximized likelihoods with the observed data. Two measures are introduced, under the null and alternative hypothesis respectively. We exemplify the measures on data coming from mapping studies on the inflammatory bowel disease and diabetes. For small-sample problems, which appear rather frequently in practice and sometimes in disguised forms (e.g., measuring individual contributions to a large study), the robust Bayesian approach holds great promise, though the choice of a general-purpose "default prior" is a very challenging problem.
Although the interest in the the use of social and information networks has grown, most inferences on networks assume the data collected represents the complete. However, when ignoring missing data, even when missing completely at random, this results in bias for estimators regarding inference network related parameters. In this paper, we focus on constructing estimators for the probability that a randomly selected node has node has at least one edge under the assumption that nodes are missing completely at random along with their corresponding edges. In addition, issues also arise in obtainin…
Statistical methods are developed for analysis of clinical and virus genetics data from phase 3 randomized, placebo-controlled trials of vaccines against novel coronavirus COVID-19. Vaccine efficacy (VE) of a vaccine to prevent COVID-19 caused by one of finitely many genetic strains of SARS-CoV-2 may vary by strain. The problem of assessing differential VE by viral genetics can be formulated under a competing risks model where the endpoint is virologically confirmed COVID-19 and the cause-of-failure is the infecting SARS-CoV-2 genotype. Strain-specific VE is defined as one minus the cause-spec…
In this paper we develop a general framework for quantifying how binary risk factors jointly influence a binary outcome. Our key result is an additive expansion of odds ratios as a sum of marginal effects and interaction terms of varying order. These odds ratio expansions are used for estimating the excess odds ratio, attributable proportion and synergy index for a case-control dataset by means of maximum likelihood from a logistic regression model. The confidence intervals associated with these estimates of joint effects and interaction of risk factors rely on the delta method. Our methodolog…
Clustering methods are a valuable tool for the identification of patterns in high dimensional data with applications in many scientific problems. However, quantifying uncertainty in clustering is a challenging problem, particularly when dealing with High Dimension Low Sample Size (HDLSS) data. We develop here a U-statistics based clustering approach that assesses statistical significance in clustering and is specifically tailored to HDLSS scenarios. These non-parametric methods rely on very few assumptions about the data, and thus can be applied to a wide range of datasets for which the euclid…
In genetic epidemiological studies, family history data are collected on relatives of study participants and used to estimate the age-specific risk of disease for individuals who carry a causal mutation. However, a family member's genotype data may not be collected due to the high cost of in-person interview to obtain blood sample or death of a relative. Previously, efficient nonparametric genotype-specific risk estimation in censored mixture data has been proposed without considering covariates. With multiple predictive risk factors available, risk estimation requires a multivariate model to …
UC San Diego（加州大学圣地亚哥分校）；University of Washington（华盛顿大学）；Northeastern University（东北大学）
Deep learning is gaining increasing popularity for spatiotemporal forecasting. However, prior works have mostly focused on point estimates without quantifying the uncertainty of the predictions. In high stakes domains, being able to generate probabilistic forecasts with confidence intervals is critical to risk assessment and decision making. Hence, a systematic study of uncertainty quantification (UQ) methods for spatiotemporal forecasting is missing in the community. In this paper, we describe two types of spatiotemporal forecasting problems: regular grid-based and graph-based. Then we analyz…
It is common in instrumental variable studies for instrument values to be missing, for example when the instrument is a genetic test in Mendelian randomization studies. In this paper we discuss two apparent paradoxes that arise in so-called single consent designs where there is one-sided noncompliance, i.e., where unencouraged units cannot access treatment. The first paradox is that, even under a missing completely at random assumption, a complete-case analysis is biased when knowledge of one-sided noncompliance is taken into account; this is not the case when such information is disregarded. …
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…
Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation (SRMI), also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we…
Sensitivity Analysis is a framework to assess how conclusions drawn from missing outcome data may be vulnerable to departures from untestable underlying assumptions. We extend the E-value, a popular metric for quantifying robustness of causal conclusions, to the setting of missing outcomes. With motivating examples from partially-observed Facebook conversion events, we present methodology for conducting Sensitivity Analysis at scale with three contributions. First, we develop a method for the Bayesian estimation of sensitivity parameters leveraging noisy benchmarks(e.g., aggregated reports for…
Family studies provide an important tool for understanding etiology of diseases, with the key aim of discovering evidence of family aggregation and to determine if such aggregation can be attributed to genetic components. Heritability and concordance estimates are routinely calculated in twin studies of diseases, as a way of quantifying such genetic contribution. The endpoint in these studies are typically defined as occurrence of a disease versus death without the disease. However, a large fraction of the subjects may still be alive at the time of follow-up without having experienced the dise…
In some multivariate problems with missing data, pairs of variables exist that are never observed together. For example, some modern biological tools can produce data of this form. As a result of this structure, the covariance matrix is only partially identifiable, and point estimation requires that identifying assumptions be made. These assumptions can introduce an unknown and potentially large bias into the inference. This paper presents a method based on semidefinite programming for automatically quantifying this potential bias by computing the range of possible equal-likelihood inferred va…
Missing data is an important challenge when dealing with high dimensional data arranged in the form of an array. In this paper, we propose methods for estimation of the parameters of array variate normal probability model from partially observed multiway data. The methods developed here are useful for missing data imputation, estimation of mean and covariance parameters for multiway data. A multiway semi-parametric mixed effects model that allows separation of multiway covariance effects is also defined and an efficient algorithm for estimation is recommended. We provide simulation results alo…
Augmented transfer regression learning for completely missing covariates
School of Mathematics and Statistics, Huazhong University of Science and Technology（华中科技大学数学与统计学院）；Department of Statistics, Colorado State University（科罗拉多州立大学统计学系）
The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifica…
