cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.8191850
title: Main Effects and Interactions in Mixed and Incomplete Data Frames

description: A mixed data frame (MDF) is a table collecting categorical, numerical, and count observations. The use of MDF is widespread in statistics and the applications are numerous from abundance data in ecology to recommender systems. In many cases, an MDF exhibits simultaneously <i>main effects</i>, such as row, column, or group effects and <i>interactions</i>, for which a low-rank model has often been suggested. Although the literature on low-rank approximations is very substantial, with few exceptions, existing methods do not allow to incorporate main effects and interactions while providing statistical guarantees. The present work fills this gap. We propose an estimation method which allows to recover simultaneously the main effects and the interactions. We show that our method is near optimal under conditions which are met in our targeted applications. We also propose an optimization algorithm which provably converges to an optimal solution. Numerical experiments reveal that our method, mimi, performs well when the main effects are sparse and the interaction matrix has low-rank. We also show that mimi compares favorably to existing methods, in particular when the main effects are significantly large compared to the interactions, and when the proportion of missing entries is large. The method is available as an R package on the Comprehensive R Archive Network. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.8295638.v3
title: Tests for Scale Changes Based on Pairwise Differences

description: In many applications it is important to know whether the amount of fluctuation in a series of observations changes over time. In this article, we investigate different tests for detecting changes in the scale of mean-stationary time series. The classical approach, based on the CUSUM test applied to the squared centered observations, is very vulnerable to outliers and impractical for heavy-tailed data, which leads us to contemplate test statistics based on alternative, less outlier-sensitive scale estimators. It turns out that the tests based on Gini’s mean difference (the average of all pairwise distances) and generalized <i>Q<sub>n</sub> </i> estimators (sample quantiles of all pairwise distances) are very suitable candidates. They improve upon the classical test not only under heavy tails or in the presence of outliers, but also under normality. We use recent results on the process convergence of <i>U</i>-statistics and <i>U</i>-quantiles for dependent sequences to derive the limiting distribution of the test statistics and propose estimators for the long-run variance. We show the consistency of the tests and demonstrate the applicability of the new change-point detection methods at two real-life data examples from hydrology and finance. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.9816446.v3
title: Genetic Variant Set-Based Tests Using the Generalized Berk–Jones Statistic With Application to a Genome-Wide Association Study of Breast Cancer

description: Studying the effects of groups of single nucleotide polymorphisms (SNPs), as in a gene, genetic pathway, or network, can provide novel insight into complex diseases such as breast cancer, uncovering new genetic associations and augmenting the information that can be gleaned from studying SNPs individually. Common challenges in set-based genetic association testing include weak effect sizes, correlation between SNPs in a SNP-set, and scarcity of signals, with individual SNP effects often ranging from extremely sparse to moderately sparse in number. Motivated by these challenges, we propose the Generalized Berk–Jones (GBJ) test for the association between a SNP-set and outcome. The GBJ extends the Berk–Jones statistic by accounting for correlation among SNPs, and it provides advantages over the Generalized Higher Criticism test when signals in a SNP-set are moderately sparse. We also provide an analytic <i>p</i>-value calculation for SNP-sets of any finite size, and we develop an omnibus statistic that is robust to the degree of signal sparsity. An additional advantage of our work is the ability to conduct inference using individual SNP summary statistics from a genome-wide association study (GWAS). We evaluate the finite sample performance of the GBJ through simulation and apply the method to identify breast cancer risk genes in a GWAS conducted by the Cancer Genetic Markers of Susceptibility Consortium. Our results suggest evidence of association between FGFR2 and breast cancer and also identify other potential susceptibility genes, complementing conventional SNP-level analysis. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.9816452.v4
title: Bayesian Nonparametric Policy Search With Application to Periodontal Recall Intervals

description: Tooth loss from periodontal disease is a major public health burden in the United States. Standard clinical practice is to recommend a dental visit every six months; however, this practice is not evidence-based, and poor dental outcomes and increasing dental insurance premiums indicate room for improvement. We consider a tailored approach that recommends recall time based on patient characteristics and medical history to minimize disease progression without increasing resource expenditures. We formalize this method as a dynamic treatment regime which comprises a sequence of decisions, one per stage of intervention, that follow a decision rule which maps current patient information to a recommendation for their next visit time. The dynamics of periodontal health, visit frequency, and patient compliance are complex, yet the estimated optimal regime must be interpretable to domain experts if it is to be integrated into clinical practice. We combine nonparametric Bayesian dynamics modeling with policy-search algorithms to estimate the optimal dynamic treatment regime within an interpretable class of regimes. Both simulation experiments and application to a rich database of electronic dental records from the HealthPartners HMO shows that our proposed method leads to better dental health without increasing the average recommended recall time relative to competing methods. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.10269596
title: Predicting Clinical Outcomes in Glioblastoma: An Application of Topological and Functional Data Analysis

description: Glioblastoma multiforme (GBM) is an aggressive form of human brain cancer that is under active study in the field of cancer biology. Its rapid progression and the relative time cost of obtaining molecular data make other readily available forms of data, such as images, an important resource for actionable measures in patients. Our goal is to use information given by medical images taken from GBM patients in statistical settings. To do this, we design a novel statistic—the smooth Euler characteristic transform (SECT)—that quantifies magnetic resonance images of tumors. Due to its well-defined inner product structure, the SECT can be used in a wider range of functional and nonparametric modeling approaches than other previously proposed topological summary statistics. When applied to a cohort of GBM patients, we find that the SECT is a better predictor of clinical outcomes than both existing tumor shape quantifications and common molecular assays. Specifically, we demonstrate that SECT features alone explain more of the variance in GBM patient survival than gene expression, volumetric features, and morphometric features. The main takeaways from our findings are thus 2-fold. First, they suggest that images contain valuable information that can play an important role in clinical prognosis and other medical decisions. Second, they show that the SECT is a viable tool for the broader study of medical imaging informatics. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.10269596.v1
title: Predicting Clinical Outcomes in Glioblastoma: An Application of Topological and Functional Data Analysis

description: Glioblastoma multiforme (GBM) is an aggressive form of human brain cancer that is under active study in the field of cancer biology. Its rapid progression and the relative time cost of obtaining molecular data make other readily available forms of data, such as images, an important resource for actionable measures in patients. Our goal is to use information given by medical images taken from GBM patients in statistical settings. To do this, we design a novel statistic—the smooth Euler characteristic transform (SECT)—that quantifies magnetic resonance images of tumors. Due to its well-defined inner product structure, the SECT can be used in a wider range of functional and nonparametric modeling approaches than other previously proposed topological summary statistics. When applied to a cohort of GBM patients, we find that the SECT is a better predictor of clinical outcomes than both existing tumor shape quantifications and common molecular assays. Specifically, we demonstrate that SECT features alone explain more of the variance in GBM patient survival than gene expression, volumetric features, and morphometric features. The main takeaways from our findings are thus 2-fold. First, they suggest that images contain valuable information that can play an important role in clinical prognosis and other medical decisions. Second, they show that the SECT is a viable tool for the broader study of medical imaging informatics. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.8295638.v2
title: Tests for Scale Changes Based on Pairwise Differences

description: In many applications it is important to know whether the amount of fluctuation in a series of observations changes over time. In this article, we investigate different tests for detecting changes in the scale of mean-stationary time series. The classical approach, based on the CUSUM test applied to the squared centered observations, is very vulnerable to outliers and impractical for heavy-tailed data, which leads us to contemplate test statistics based on alternative, less outlier-sensitive scale estimators. It turns out that the tests based on Gini’s mean difference (the average of all pairwise distances) and generalized <i>Q<sub>n</sub> </i> estimators (sample quantiles of all pairwise distances) are very suitable candidates. They improve upon the classical test not only under heavy tails or in the presence of outliers, but also under normality. We use recent results on the process convergence of <i>U</i>-statistics and <i>U</i>-quantiles for dependent sequences to derive the limiting distribution of the test statistics and propose estimators for the long-run variance. We show the consistency of the tests and demonstrate the applicability of the new change-point detection methods at two real-life data examples from hydrology and finance. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.8015966.v2
title: Distance-Based Analysis of Ordinal Data and Ordinal Time Series

description: The dissimilarity of ordinal categories can be expressed with a distance measure. A unified approach relying on expected distances is proposed to obtain well-interpretable measures of location, dispersion, or symmetry of random variables, as well as measures of serial dependence within a given process. For special types of distance, these analytic tools lead to known approaches for ordinal or real-valued random variables. We also analyze the sample counterparts of the proposed measures and derive asymptotic results for practically important cases in ordinal data and time series analysis. Two real applications about the economic situation in Germany and the credit rating of European countries are presented. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.8191850.v3
title: Main Effects and Interactions in Mixed and Incomplete Data Frames

description: A mixed data frame (MDF) is a table collecting categorical, numerical, and count observations. The use of MDF is widespread in statistics and the applications are numerous from abundance data in ecology to recommender systems. In many cases, an MDF exhibits simultaneously <i>main effects</i>, such as row, column, or group effects and <i>interactions</i>, for which a low-rank model has often been suggested. Although the literature on low-rank approximations is very substantial, with few exceptions, existing methods do not allow to incorporate main effects and interactions while providing statistical guarantees. The present work fills this gap. We propose an estimation method which allows to recover simultaneously the main effects and the interactions. We show that our method is near optimal under conditions which are met in our targeted applications. We also propose an optimization algorithm which provably converges to an optimal solution. Numerical experiments reveal that our method, mimi, performs well when the main effects are sparse and the interaction matrix has low-rank. We also show that mimi compares favorably to existing methods, in particular when the main effects are significantly large compared to the interactions, and when the proportion of missing entries is large. The method is available as an R package on the Comprehensive R Archive Network. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.8307563
title: Estimating Optimal Dynamic Treatment Regimes With Survival Outcomes

description: The statistical study of precision medicine is concerned with dynamic treatment regimes (DTRs) in which treatment decisions are tailored to patient-level information. Individuals are followed through multiple stages of clinical intervention, and the goal is to perform inferences on the sequence of personalized treatment decision rules to be applied in practice. Of interest is the identification of an optimal DTR, that is, the sequence of treatment decisions that yields the best expected outcome. Statistical methods for identifying optimal DTRs from observational data are theoretically complex and not easily implementable by researchers, especially when the outcome of interest is survival time. We propose a doubly robust, easy to implement method for estimating optimal DTRs with survival endpoints subject to right-censoring which requires solving a series of weighted generalized estimating equations. We provide a proof of consistency that relies on the balancing property of the weights and derive a formula for the asymptotic variance of the resulting estimators. We illustrate our novel approach with an application to the treatment of rheumatoid arthritis using observational data from the Scottish Early Rheumatoid Arthritis Inception Cohort. Our method, called dynamic weighted survival modeling, has been implemented in the DTRreg R package. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.10113239
title: Fine-Scale Spatiotemporal Air Pollution Analysis Using Mobile Monitors on Google Street View Vehicles

description: People are increasingly concerned with understanding their personal environment, including possible exposure to harmful air pollutants. To make informed decisions on their day-to-day activities, they are interested in real-time information on a localized scale. Publicly available, fine-scale, high-quality air pollution measurements acquired using mobile monitors represent a paradigm shift in measurement technologies. A methodological framework utilizing these increasingly fine-scale measurements to provide real-time air pollution maps and short-term air quality forecasts on a fine-resolution spatial scale could prove to be instrumental in increasing public awareness and understanding. The Google Street View study provides a unique source of data with spatial and temporal complexities, with the potential to provide information about commuter exposure and hot spots within city streets with high traffic. We develop a computationally efficient spatiotemporal model for these data and use the model to make short-term forecasts and high-resolution maps of current air pollution levels. We also show via an experiment that mobile networks can provide more nuanced information than an equally sized fixed-location network. This modeling framework has important real-world implications in understanding citizens’ personal environments, as data production and real-time availability continue to be driven by the ongoing development and improvement of mobile measurement technologies. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.9816446.v2
title: Genetic Variant Set-Based Tests Using the Generalized Berk-Jones Statistic with Application to a Genome-Wide Association Study of Breast Cancer

description: Studying the effects of groups of single nucleotide polymorphisms (SNPs), as in a gene, genetic pathway, or network, can provide novel insight into complex diseases like breast cancer, uncovering new genetic associations and augmenting the information that can be gleaned from studying SNPs individually. Common challenges in set-based genetic association testing include weak effect sizes, correlation between SNPs in a SNP-set, and scarcity of signals, with individual SNP effects often ranging from extremely sparse to moderately sparse in number. Motivated by these challenges, we propose the Generalized Berk-Jones (GBJ) test for the association between a SNP-set and outcome. The GBJ extends the Berk-Jones statistic by accounting for correlation among SNPs, and it provides advantages over the Generalized Higher Criticism test when signals in a SNP-set are moderately sparse. We also provide an analytic p-value calculation for SNP-sets of any finite size, and we develop an omnibus statistic that is robust to the degree of signal sparsity. An additional advantage of our work is the ability to conduct inference using individual SNP summary statistics from a genome-wide association study (GWAS). We evaluate the finite sample performance of the GBJ through simulation and apply the method to identify breast cancer risk genes in a GWAS conducted by the Cancer Genetic Markers of Susceptibility Consortium. Our results suggest evidence of association between FGFR2 and breast cancer and also identify other potential susceptibility genes, complementing conventional SNP-level analysis.
DOI: 10.6084/m9.figshare.9816452.v3
title: Bayesian Nonparametric Policy Search With Application to Periodontal Recall Intervals

description: Tooth loss from periodontal disease is a major public health burden in the United States. Standard clinical practice is to recommend a dental visit every six months; however, this practice is not evidence-based, and poor dental outcomes and increasing dental insurance premiums indicate room for improvement. We consider a tailored approach that recommends recall time based on patient characteristics and medical history to minimize disease progression without increasing resource expenditures. We formalize this method as a dynamic treatment regime which comprises a sequence of decisions, one per stage of intervention, that follow a decision rule which maps current patient information to a recommendation for their next visit time. The dynamics of periodontal health, visit frequency, and patient compliance are complex, yet the estimated optimal regime must be interpretable to domain experts if it is to be integrated into clinical practice. We combine nonparametric Bayesian dynamics modeling with policy-search algorithms to estimate the optimal dynamic treatment regime within an interpretable class of regimes. Both simulation experiments and application to a rich database of electronic dental records from the HealthPartners HMO shows that our proposed method leads to better dental health without increasing the average recommended recall time relative to competing methods. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
DOI: 10.6084/m9.figshare.8191850.v2
title: Main Effects and Interactions in Mixed and Incomplete Data Frames

description: A mixed data frame (MDF) is a table collecting categorical, numerical, and count observations. The use of MDF is widespread in statistics and the applications are numerous from abundance data in ecology to recommender systems. In many cases, an MDF exhibits simultaneously <i>main effects</i>, such as row, column, or group effects and <i>interactions</i>, for which a low-rank model has often been suggested. Although the literature on low-rank approximations is very substantial, with few exceptions, existing methods do not allow to incorporate main effects and interactions while providing statistical guarantees. The present work fills this gap. We propose an estimation method which allows to recover simultaneously the main effects and the interactions. We show that our method is near optimal under conditions which are met in our targeted applications. We also propose an optimization algorithm which provably converges to an optimal solution. Numerical experiments reveal that our method, mimi, performs well when the main effects are sparse and the interaction matrix has low-rank. We also show that mimi compares favorably to existing methods, in particular when the main effects are significantly large compared to the interactions, and when the proportion of missing entries is large. The method is available as an R package on the Comprehensive R Archive Network. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.9955001
title: A Likelihood Ratio Approach to Sequential Change Point Detection for a General Class of Parameters

description: In this article, we propose a new approach for sequential monitoring of a general class of parameters of a <i>d</i>-dimensional time series, which can be estimated by approximately linear functionals of the empirical distribution function. We consider a closed-end method, which is motivated by the likelihood ratio test principle and compare the new method with two alternative procedures. We also incorporate self-normalization such that estimation of the long-run variance is not necessary. We prove that for a large class of testing problems the new detection scheme has asymptotic level <i>α</i> and is consistent. The asymptotic theory is illustrated for the important cases of monitoring a change in the mean, variance, and correlation. By means of a simulation study it is demonstrated that the new test performs better than the currently available procedures for these problems. Finally, the methodology is illustrated by a small data example investigating index prices from the dot-com bubble. Supplementary materials for this article are available online.