Disaggregation regression has become an important tool in spatial disease mapping for making fine-scale predictions of disease risk from aggregated response data. By including high resolution covariate information and modelling the data generating process on a fine scale, it is hoped that these models can accurately learn the relationships between covariates and response at a fine spatial scale. However, validating these high resolution predictions can be a challenge, as often there is no data observed at this spatial scale. In this study, disaggregation regression was performed on simulated data in various settings and the resulting fine-scale predictions are compared to the simulated ground truth. Performance was investigated with varying numbers of data points, sizes of aggregated areas and levels of model misspecification. The effectiveness of cross validation on the aggregate level as a measure of fine-scale predictive performance was also investigated. Predictive performance improved as the number of observations increased and as the size of the aggregated areas decreased. When the model was well-specified, fine-scale predictions were accurate even with small numbers of observations and large aggregated areas. Under model misspecification predictive performance was significantly worse for large aggregated areas but remained high when response data was aggregated over smaller regions. Cross-validation correlation on the aggregate level was a moderately good predictor of fine-scale predictive performance. While the simulations are unlikely to capture the nuances of real-life response data, this study gives insight into the effectiveness of disaggregation regression in different contexts.
Integrating Temporal Disaggregation and Distributed Lag Nonlinear Models for Bayesian Spatio-Temporal Disease Mapping with High-Resolution Environmental Exposures
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）；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）
The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive numbers of zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We prop…
Several gene-based association tests for time-to-event traits have been proposed recently, to detect whether a gene region (containing multiple variants), as a set, is associated with the survival outcome. However, for bivariate survival outcomes, to the best of our knowledge, there is no statistical method that can be directly applied for gene-based association analysis. Motivated by a genetic study to discover gene regions associated with the progression of a bilateral eye disease, Age-related Macular Degeneration (AMD), we implement a novel functional regression method under the copula fram…
With the resurgence of tick-borne diseases such as Lyme disease and the emergence of new pathogens such as Powassan virus, understanding what distinguishes vector from non-vector species, and predicting undiscovered tick vectors is an important step towards mitigating human disease risk. We apply generalized boosted regression to interrogate over 90 features for over 240 species of Ixodes ticks. Our model predicted vector status with ~97% accuracy and implicated 14 tick species whose intrinsic trait profiles confer high probabilities (~80%) that they are capable of transmitting infections from…
Genome-wide association studies have proven to be essential for understanding the genetic basis of disease. However, many complex traits---personality traits, facial features, disease subtyping---are inherently high-dimensional, impeding simple approaches to association mapping. We developed a nonparametric Bayesian reduced rank regression model for multi-SNP, multi-trait association mapping that does not require the rank of the linear subspace to be specified. We show in simulations and real data that our model shares strength over SNPs and over correlated traits, improving statistical power …
Truncation is a statistical phenomenon that occurs in many time to event studies. For example, autopsy-confirmed studies of neurodegenerative diseases are subject to an inherent left and right truncation, also known as double truncation. When the goal is to study the effect of risk factors on survival, the standard Cox regression model cannot be used when the data is subject to truncation. Existing methods which adjust for both left and right truncation in the Cox regression model require independence between the survival times and truncation times, which may not be a reasonable assumption in …
One of the major developments in recent years in the search for missing heritability of human phenotypes is the adoption of linear mixed-effects models (LMMs) to estimate heritability due to genetic variants which are not significantly associated with the phenotype. A variant of the LMM approach has been adapted to case-control studies and applied to many major diseases by Lee et al. (2011), successfully accounting for a considerable portion of the missing heritability. For example, for Crohn's disease their estimated heritability was 22% compared to 50-60% from family studies. In this letter …
Burden of disease measures the impact of living with illness and injury and dying prematurely and it is increasing worldwide leading cause of death both global and national. This paper aimed to propose an index of diseases and evaluate a mathematical model to describe the number of burden of disease by cause in the Philippines from 1990 - 2016. Through Principal Component Analysis (PCA) the diseases categorized as: passed on diseases, vector born diseases, non-communicable diseases, accident, and intentional. Symbolic Regression Analysis was carried out, the study revealed that the number of b…
Many common diseases are highly polygenic, modulated by a large number genetic factors with small effects on susceptibility to disease. These small effects are difficult to map reliably in genetic association studies. To address this problem, researchers have developed methods that aggregate information over sets of related genes, such as biological pathways, to identify gene sets that are enriched for genetic variants associated with disease. However, these methods fail to answer a key question: which genes and genetic variants are associated with disease risk? We develop a method based on sp…
2 Diabetes is a leading worldwide public health concern, and its increasing prevalence has significant health and economic importance in all nations. The condition is a multifactorial disorder with a complex aetiology. The genetic determinants remain largely elusive, with only a handful of identified candidate genes. Genome wide association studies (GWAS) promised to significantly enhance our understanding of genetic based determinants of common complex diseases. To date, 83 single nucleotide polymorphisms (SNPs) for type 2 diabetes have been identified using GWAS. Standard statistical tests f…
We propose a new centered autologistic spatio-temporal model for binary data on a lattice. The centering allows the interpretation of the autoregression coefficients in separating the large scale structure of the model corresponding to an expected mean and the small-scale structure corresponding to the auto-correlation. We discuss the existence of the joint law of the process and show by simulation the interest of this kind of centering. We propose and show the efficiency of the maximum pseudo-likelihood estimator and also a method to choose the best structure of neighborhood. Method is applie…
The cause-specific cumulative incidence function (CIF) quantifies the subject-specific disease risk with competing risk outcome. With longitudinally collected biomarker data, it is of interest to dynamically update the predicted CIF by incorporating the most recent biomarker as well as the cumulating longitudinal history. Motivated by a longitudinal cohort study of chronic kidney disease, we propose a framework for dynamic prediction of end stage renal disease using multivariate longitudinal biomarkers, accounting for the competing risk of death. The proposed framework extends the landmark sur…
The emergence of Covid-19 requires new effective tools for epidemiological surveillance. Spatio-temporal disease mapping models, which allow dealing with highly disaggregated spatial and temporal units of analysis, are a priority in this sense. Spatio-temporal models provide a geographically detailed and temporally updated overview of the current state of the pandemics, making public health interventions to be more effective. Moreover, the use of spatio-temporal disease mapping models in the new Covid-19 epidemic context, facilitates estimating newly demanded epidemiological indicators, such a…
Motivated by analyzing a national data base of annual air pollution and cardiovascular disease mortality rate for 3100 counties in the U.S. (areal data), we develop a novel statistical framework to automatically detect spatially varying region-wise associations between air pollution exposures and health outcomes. The automatic region-wise spatially varying coefficient model consists three parts: we first compute the similarity matrix between the exposure-health outcome associations of all spatial units, then segment the whole map into a set of disjoint regions based on the adjacency matrix wit…
Wearable data is a rich source of information that can provide deeper understanding of links between human behaviours and human health. Existing modelling approaches use wearable data summarized at subject level via scalar summaries using regression techniques, temporal (time-of-day) curves using functional data analysis (FDA), and distributions using distributional data analysis (DDA). We propose to capture temporally local distributional information in wearable data using subject-specific time-by-distribution (TD) data objects. Specifically, we propose scalar on time-by-distribution regressi…
Brain segmentation at different levels is generally represented as hierarchical trees. Brain regional atrophy at specific levels was found to be marginally associated with Alzheimer's disease outcomes. In this study, we propose an L1-type regularization for predictors that follow a hierarchical tree structure. Considering a tree as a directed acyclic graph, we interpret the model parameters from a path analysis perspective. Under this concept, the proposed penalty regulates the total effect of each predictor on the outcome. With regularity conditions, it is shown that under the proposed regula…
To study the impact of climate variables on morbidity of some diseases in Mexico, we propose a spatio-temporal varying coefficients regression model. For that we introduce a new spatio-temporal dependent process prior, in a Bayesian context, with identically distributed normal marginal distributions and joint multivariate normal distribution. We study its properties and characterise the dependence induced. Our results show that the effect of climate variables, on the incidence of specific diseases, is not constant across space and time and our proposed model is able to capture and quantify tho…
We consider high-dimensional regression over subgroups of observations. Our work is motivated by biomedical problems, where disease subtypes, for example, may differ with respect to underlying regression models, but sample sizes at the subgroup-level may be limited. We focus on the case in which subgroup-specific models may be expected to be similar but not necessarily identical. Our approach is to treat subgroups as related problem instances and jointly estimate subgroup-specific regression coefficients. This is done in a penalized framework, combining an $\ell_1$ term with an additional term…
Falls are detrimental to people with Parkinson's Disease (PD) because of the potentially severe consequences to the patients' quality of life. While many studies have attempted to predict falls/non-falls, this study aimed to determine factors related to falls frequency in people with early PD. Ninety nine participants with early stage PD were assessed based on two types of tests. The first type of tests is disease-specific tests, comprised of the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab and England activities of daily living scale (SEADL). A measure of postural instabili…
Background: Recent systematic reviews of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS) revealed a decrease in placebo annualized relapse rates (ARR) over the past two decades. Furthermore, regression to the mean effects were observed in ARR and MRI lesion counts. It is unclear whether disease progression measured by the expanded disability status scale (EDSS) exhibits similar features. Methods: A systematic review of RCTs in RMS was conducted extracting data on EDSS and baseline characteristics. The logarithmic odds of disease progression were modelled to investigat…
The genetic etiologies of common diseases are highly complex and heterogeneous. Classic statistical methods, such as linear regression, have successfully identified numerous genetic variants associated with complex diseases. Nonetheless, for most complex diseases, the identified variants only account for a small proportion of heritability. Challenges remain to discover additional variants contributing to complex diseases. Expectile regression is a generalization of linear regression and provides completed information on the conditional distribution of a phenotype of interest. While expectile r…
This paper develops a large-scale Bayesian spatio-temporal binomial regression model for the purpose of investigating regional trends in antibody prevalence to Borrelia burgdorferi, the causative agent of Lyme disease. The proposed model uses Gaussian predictive processes to estimate the spatially varying trends and a conditional autoregressive model to account for spatio-temporal dependence. Careful consideration is made to develop a novel framework that is scalable to large spatio-temporal data. The proposed model is used to analyze approximately 16 million Borrelia burgdorferi test results …
In large-scale disease etiology studies, epidemiologists often need to use multiple binary measures of unobserved causes of disease that are not perfectly sensitive or specific to estimate cause-specific case fractions, referred to as "population etiologic fractions" (PEFs). Despite recent methodological advances, the scientific need of incorporating control data to estimate the effect of explanatory variables upon the PEFs, however, remains unmet. In this paper, we build on and extend nested partially-latent class model (npLCMs, Wu et al., 2017) to a general framework for etiology regression …
Microbiome `omics approaches can reveal intriguing relationships between the human microbiome and certain disease states. Along with the identification of specific bacteria taxa associated with diseases, recent scientific advancements provide mounting evidence that metabolism, genetics and environmental factors can all modulate these microbial effects. However, the current methods for integrating microbiome data and other covariates are severely lacking. Hence, we present an integrative Bayesian zero-inflated negative binomial regression model that can both distinguish differentially abundant …
We present a new method for the detection of gene pathways associated with a multivariate quantitative trait, and use it to identify causal pathways associated with an imaging endophenotype characteristic of longitudinal structural change in the brains of patients with Alzheimer's disease (AD). Our method, known as pathways sparse reduced-rank regression (PsRRR), uses group lasso penalised regression to jointly model the effects of genome-wide single nucleotide polymorphisms (SNPs), grouped into functional pathways using prior knowledge of gene-gene interactions. Pathways are ranked in order o…
There is no gold standard for the diagnosis of Alzheimer's disease (AD), except from autopsies. Unsupervised learning can provide insight into the pathophysiology of AD. A mixture of regressions can simultaneously identify clusters from multiple biomarkers while accounting for within-cluster demographic effects. Cerebrospinal fluid (CSF) biomarkers for AD have detection limits, which create additional challenges. We apply a mixture of regressions with a multivariate truncated Gaussian distribution (also called a censored multivariate Gaussian mixture of regressions or a mixture of multivariate…
Bayesian Profile Regression using Variational Inference to Identify Clusters of Multiple Long-Term Conditions Conditioning on Mortality in Population-Scale Data
Health Data Research UK, Swansea University Medical School, Swansea University（英国健康数据研究中心，斯旺西大学医学院，斯旺西大学）；Department of Statistics, University of Warwick（华威大学统计系）；Department of Pharmacology and Therapeutics, University of Liverpool（利物浦大学药理学与治疗学系）；Division of Cancer and Genetics, Cardiff University（卡迪夫大学癌症与遗传学部）
In certain genetic studies, clinicians and genetic counselors are interested in estimating the cumulative risk of a disease for individuals with and without a rare deleterious mutation. Estimating the cumulative risk is difficult, however, when the estimates are based on family history data. Often, the genetic mutation status in many family members is unknown; instead, only estimated probabilities of a patient having a certain mutation status are available. Also, ages of disease-onset are subject to right censoring. Existing methods to estimate the cumulative risk using such family-based data …
This paper describes a new neuroimaging analysis toolbox that allows for the modeling of nonlinear effects at the voxel level, overcoming limitations of methods based on linear models like the GLM. We illustrate its features using a relevant example in which distinct nonlinear trajectories of Alzheimer's disease related brain atrophy patterns were found across the full biological spectrum of the disease. The open-source toolbox presented in this paper is available at https://github.com/imatge-upc/VNeAT.
Penalized Fair Regression for Multiple Groups in Chronic Kidney Disease
Department of Health Policy, Stanford University（健康政策系，斯坦福大学）；Stanford University（斯坦福大学）；Department of Epidemiology and Population Health, Stanford University（流行病学与人口健康系，斯坦福大学）
Medical imaging studies have collected high dimensional imaging data to identify imaging biomarkers for diagnosis, screening, and prognosis, among many others. These imaging data are often represented in the form of a multi-dimensional array, called a tensor. The aim of this paper is to develop a tensor partition regression modeling (TPRM) framework to establish a relationship between low-dimensional clinical outcomes (e.g., diagnosis) and high dimensional tensor covariates. Our TPRM is a hierarchical model and efficiently integrates four components: (i) a partition model, (ii) a canonical pol…
In the recent past, electronic health records and distributed data networks emerged as a viable resource for medical and scientific research. As the use of confidential patient information from such sources become more common, maintaining privacy of patients is of utmost importance. For a binary disease outcome of interest, we show that the techniques of microaggregation (equivalent to specimen pooling) and \underline{Po}oled \underline{Lo}gistic \underline{R}egression (PoLoR) could be applied for analysis of large and/or distributed data while respecting patient privacy. PoLoR is exactly the …
Alzheimer's disease is a neurodegenerative condition that accelerates cognitive decline relative to normal aging. It is of critical scientific importance to gain a better understanding of early disease mechanisms in the brain to facilitate effective, targeted therapies. The volume of the hippocampus is often used in diagnosis and monitoring of the disease. Measuring this volume via neuroimaging is difficult since each hippocampus must either be manually identified or automatically delineated, a task referred to as segmentation. Automatic hippocampal segmentation often involves mapping a previo…
Lyme disease is an infectious disease that is caused by a bacterium called Borrelia burgdorferi sensu stricto. In the United States, Lyme disease is one of the most common infectious diseases. The major endemic areas of the disease are New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central. Virginia is on the front-line of the disease's diffusion from the northeast to the south. One of the research objectives for the infectious disease community is to identify environmental and economic variables that are associated with the emergence of Lyme disease. In this pap…
In this paper, we apply statistical methods for functional data to explain the heterogeneity in the evolution of number of deaths of Covid-19 over different regions. We treat the cumulative daily number of deaths in a specific region as a curve (functional data) such that the data comprise of a set of curves over a cross-section of locations. We start by using clustering methods for functional data to identify potential heterogeneity in the curves and their functional derivatives. This first stage is an unconditional descriptive analysis, as we do not use any covariate to estimate the clusters…
International Classification of Disease (ICD) codes are widely used for encoding diagnoses in electronic health records (EHR). Automated methods have been developed over the years for predicting biomedical responses using EHR that borrow information among diagnostically similar patients. Relatively less attention has been paid to developing patient similarity measures that model the structure of ICD codes and the presence of multiple chronic conditions, where a chronic condition is defined as a set of ICD codes. Motivated by this problem, we first develop a type of string kernel function for m…
Graphical models are commonly used to discover associations within gene or protein networks for complex diseases such as cancer. Most existing methods estimate a single graph for a population, while in many cases, researchers are interested in characterizing the heterogeneity of individual networks across subjects with respect to subject-level covariates. Examples include assessments of how the network varies with patient-specific prognostic scores or comparisons of tumor and normal graphs while accounting for tumor purity as a continuous predictor. In this paper, we propose a novel edge regre…
In order for clinicians to manage disease progression and make effective decisions about drug dosage, treatment regimens or scheduling follow up appointments, it is necessary to be able to identify both short and long-term trends in repeated biomedical measurements. However, this is complicated by the fact that these measurements are irregularly sampled and influenced by both genuine physiological changes and external factors. In their current forms, existing regression algorithms often do not fulfil all of a clinician's requirements for identifying short-term events while still being able to …
Balancing a rare and serious possibility against a more common and less serious one is a familiar problem in many situations, such as the prediction of rare diseases. The relative costs of forecasting errors can be used for any prediction method that gives an estimated probability of a future event. The probability at which the likely cost (defined as cost x probability) of a possible false negative is exactly equal to that of a possible false positive gives the relevant cutpoint and all subjects with probability of disease greater than this have a positive test result. All standard methods of…
This study presents application examples of generalized spatial regression modeling for count data and continuous non-Gaussian data using the spmoran package (version 0.2.2 onward). Section 2 introduces the model. The subsequent sections demonstrate applications of the model for disease mapping, spatial prediction and uncertainty modeling, and hedonic analysis. The R codes used in this vignette are available from https://github.com/dmuraka/spmoran. Another vignette focusing on Gaussian spatial regression modeling is also available from the same GitHub page.
Seasonal influenza is a sometimes surprisingly impactful disease, causing thousands of deaths per year along with much additional morbidity. Timely knowledge of the outbreak state is valuable for managing an effective response. The current state of the art is to gather this knowledge using in-person patient contact. While accurate, this is time-consuming and expensive. This has motivated inquiry into new approaches using internet activity traces, based on the theory that lay observations of health status lead to informative features in internet data. These approaches risk being deceived by act…
Sheep pox is a highly transmissible disease which can cause serious loss of livestock and can therefore have major economic impact. We present data from sheep pox epidemics which occurred between 1994 and 1998. The data include weekly records of infected farms as well as a number of covariates. We implement Bayesian stochastic regression models which, in addition to various explanatory variables like seasonal and environmental/meteorological factors, also contain serial correlation structure based on variants of the Ornstein-Uhlenbeck process. We take a predictive view in model selection by ut…
We propose new parametric frameworks of regression analysis with the conditional mode of a bounded response as the focal point of interest. Covariate effects estimation and prediction based on the maximum likelihood method under two new classes of regression models are demonstrated. We also develop graphical and numerical diagnostic tools to detect various sources of model misspecification. Predictions based on different central tendency measures inferred using various regression models are compared using synthetic data in simulations. Finally, we conduct regression analysis for data from the …
This paper studies the problem of statistical inference for genetic relatedness between binary traits based on individual-level genome-wide association data. Specifically, under the high-dimensional logistic regression models, we define parameters characterizing the cross-trait genetic correlation, the genetic covariance and the trait-specific genetic variance. A novel weighted debiasing method is developed for the logistic Lasso estimator and computationally efficient debiased estimators are proposed. The rates of convergence for these estimators are studied and their asymptotic normality is …
The percentage of patients hospitalized due to hyponatremia is getting higher. Hyponatremia is the deficiency of sodium electrolyte in the human serum. This deficiency might indulge adverse effects and also associated with longer hospital stay or mortality, if it wasnt actively treated and managed. This work predicts the futuristic sodium levels of patients based on their history of health problems using multilayer perceptron and multivariate linear regression algorithm. This work analyses the patients age, information about other disease such as diabetes, pneumonia, liver-disease, malignancy,…
Heterogeneity is a hallmark of complex diseases. Regression-based heterogeneity analysis, which is directly concerned with outcome-feature relationships, has led to a deeper understanding of disease biology. Such an analysis identifies the underlying subgroup structure and estimates the subgroup-specific regression coefficients. However, most of the existing regression-based heterogeneity analyses can only address disjoint subgroups; that is, each sample is assigned to only one subgroup. In reality, some samples have multiple labels, for example, many genes have several biological functions, a…
Leiden University（莱顿大学）；Leiden University Medical Center（莱顿大学医学中心）；Leiden Institute for Brain and Cognition（莱顿脑与认知研究所）；Bocconi University（博科尼大学）；Bocconi Institute for Data Science and Analytics（博科尼数据科学与分析研究所）；Medical University of Graz（格拉茨医科大学）
Multi-view data refers to a setting where features are divided into feature sets, for example because they correspond to different sources. Stacked penalized logistic regression (StaPLR) is a recently introduced method that can be used for classification and automatically selecting the views that are most important for prediction. We introduce an extension of this method to a setting where the data has a hierarchical multi-view structure. We also introduce a new view importance measure for StaPLR, which allows us to compare the importance of views at any level of the hierarchy. We apply our ex…
We introduce a Bayesian nonparametric regression model for data with multiway (tensor) structure, motivated by an application to periodontal disease (PD) data. Our outcome is the number of diseased sites measured over four different tooth types for each subject, with subject-specific covariates available as predictors. The outcomes are not well-characterized by simple parametric models, so we use a nonparametric approach with a binomial likelihood wherein the latent probabilities are drawn from a mixture with an arbitrary number of components, analogous to a Dirichlet Process (DP). We use a fl…
Prediction of the future trajectory of a disease is an important challenge for personalized medicine and population health management. However, many complex chronic diseases exhibit large degrees of heterogeneity, and furthermore there is not always a single readily available biomarker to quantify disease severity. Even when such a clinical variable exists, there are often additional related biomarkers routinely measured for patients that may better inform the predictions of their future disease state. To this end, we propose a novel probabilistic generative model for multivariate longitudinal…
IQIVA Inc.（艾昆纬公司）；University of Minnesota（明尼苏达大学）；University of Chicago（芝加哥大学）
Models have been proposed to extract temporal patterns from longitudinal electronic health records (EHR) for clinical predictive models. However, the common relations among patients (e.g., receiving the same medical treatments) were rarely considered. In this paper, we propose to learn patient similarity features as phenotypes from the aggregated patient-medical service matrix using non-negative matrix factorization. On real-world medical claim data, we show that the learned phenotypes are coherent within each group, and also explanatory and indicative of targeted diseases. We conducted experi…
