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Abstract We propose a resampling-based fast variable selection technique for detecting relevant single nucleotide polymorphisms (SNP) in a multi-marker mixed effect model. Due to computational complexity, current practice primarily involves testing the effect of one SNP at a time, commonly termed as ‘single SNP association analysis’. Joint modeling of genetic variants within a gene or pathway may have better power to detect associated genetic variants, especially the ones with weak effects. In this paper, we propose a computationally efficient model selection approach—based on the e-values framework—for single SNP detection in families while utilizing information on multiple SNPs simultaneously. To overcome computational bottleneck of traditional model selection methods, our method trains one single model, and utilizes a fast and scalable bootstrap procedure. We illustrate through numerical studies that our proposed method is more effective in detecting SNPs associated with a trait than either single-marker analysis using family data or model selection methods that ignore the familial dependency structure. Further, we perform gene-level analysis in Minnesota Center for Twin and Family Research (MCTFR) dataset using our method to detect several SNPs using this that have been implicated to be associated with alcohol consumption. 

Abstract We develop a technique for record linkage on high dimensional data, where the two datasets may not have any common variable, and there may be no training set available. Our methodology is based on sparse, high dimensional principal components. Since large and high dimensional datasets are often prone to outliers and aberrant observations, we propose a technique for estimating robust, high dimensional principal components. We present theoretical results validating the robust, high dimensional principal component estimation steps, and justifying their use for record linkage. Some numeric results and remarks are also presented. 

We present a new semiparametric extension of the Fay-Herriot model, termed the agnostic Fay-Herriot model (AGFH), in which the sampling-level model is expressed in terms of an unknown general function [Formula: see text]. Thus, the AGFH model can express any distribution in the sampling model since the choice of [Formula: see text] is extremely broad. We propose a Bayesian modelling scheme for AGFH where the unknown function [Formula: see text] is assigned a Gaussian Process prior. Using a Metropolis within Gibbs sampling Markov Chain Monte Carlo scheme, we study the performance of the AGFH model, along with that of a hierarchical Bayesian extension of the Fay-Herriot model. Our analysis shows that the AGFH is an excellent modelling alternative when the sampling distribution is non-Normal, especially in the case where the sampling distribution is bounded. It is also the best choice when the sampling variance is high. However, the hierarchical Bayesian framework and the traditional empirical Bayesian framework can be good modelling alternatives when the signal-to-noise ratio is high, and there are computational constraints. AMS subject classification: 62D05; 62F15 

Rapid advancement in inverse modeling methods have brought into light their susceptibility to imperfect data. This has made it imperative to obtain more explainable and trustworthy estimates from these models. In hydrology, basin characteristics can be noisy or missing, impacting streamflow prediction. We propose a probabilistic inverse model framework that can reconstruct robust hydrology basin characteristics from dynamic input weather driver and streamflow response data. We address two aspects of building more explainable inverse models, uncertainty estimation (uncertainty due to imperfect data and imperfect model) and robustness. This can help improve the trust of water managers, handling of noisy data and reduce costs. We also propose an uncertainty based loss regularization that offers removal of 17% of temporal artifacts in reconstructions, 36% reduction in uncertainty and 4% higher coverage rate for basin characteristics. The forward model performance (streamflow estimation) is also improved by 6% using these uncertainty learning based reconstructions. 

We are rapidly approaching a future in which cancer patient digital twins will reach their potential to predict cancer prevention, diagnosis, and treatment in individual patients. This will be realized based on advances in high performance computing, computational modeling, and an expanding repertoire of observational data across multiple scales and modalities. In 2020, the US National Cancer Institute, and the US Department of Energy, through a trans-disciplinary research community at the intersection of advanced computing and cancer research, initiated team science collaborative projects to explore the development and implementation of predictive Cancer Patient Digital Twins. Several diverse pilot projects were launched to provide key insights into important features of this emerging landscape and to determine the requirements for the development and adoption of cancer patient digital twins. Projects included exploring approaches to using a large cohort of digital twins to perform deep phenotyping and plan treatments at the individual level, prototyping self-learning digital twin platforms, using adaptive digital twin approaches to monitor treatment response and resistance, developing methods to integrate and fuse data and observations across multiple scales, and personalizing treatment based on cancer type. Collectively these efforts have yielded increased insights into the opportunities and challenges facing cancer patient digital twin approaches and helped define a path forward. Given the rapidly growing interest in patient digital twins, this manuscript provides a valuable early progress report of several CPDT pilot projects commenced in common, their overall aims, early progress, lessons learned and future directions that will increasingly involve the broader research community. 

We present an overview of four challenging research areas in multiscale physics and engineering as well as four data science topics that may be developed for addressing these challenges. We focus on multiscale spatiotemporal problems in light of the importance of understanding the accompanying scientific processes and engineering ideas, where “multiscale” refers to concurrent, non-trivial and coupled models over scales separated by orders of magnitude in either space, time, energy, momenta, or any other relevant parameter. Specifically, we consider problems where the data may be obtained at various resolutions; analyzing such data and constructing coupled models led to open research questions in various applications of data science. Numeric studies are reported for one of the data science techniques discussed here for illustration, namely, on approximate Bayesian computations. 

In the context of supervised parametric models, we introduce the concept of e-values. An e-value is a scalar quantity that represents the proximity of the sampling distribution of parameter estimates in a model trained on a subset of features to that of the model trained on all features (i.e. the full model). Under general conditions, a rank ordering of e-values separates models that contain all essential features from those that do not. The e-values are applicable to a wide range of parametric models. We use data depths and a fast resampling-based algorithm to implement a feature selection procedure using e-values, providing consistency results. For a p-dimensional feature space, this procedure requires fitting only the full model and evaluating p + 1 models, as opposed to the traditional requirement of fitting and evaluating 2^p models. Through experiments across several model settings and synthetic and real datasets, we establish that the e-values method as a promising general alternative to existing model-specific methods of feature selection 

Abstract Simulations of future climate contain variability arising from a number of sources, including internal stochasticity and external forcings. However, to the best of our abilities climate models and the true observed climate depend on the same underlying physical processes. In this paper, we simultaneously study the outputs of multiple climate simulation models and observed data, and we seek to leverage their mean structure as well as interdependencies that may reflect the climate’s response to shared forcings. Bayesian modeling provides a fruitful ground for the nuanced combination of multiple climate simulations. We introduce one such approach whereby a Gaussian process is used to represent a mean function common to all simulated and observed climates. Dependent random effects encode possible information contained within and between the plurality of climate model outputs and observed climate data. We propose an empirical Bayes approach to analyze such models in a computationally efficient way. This methodology is amenable to the CMIP6 model ensemble, and we demonstrate its efficacy at forecasting global average near-surface air temperature. Results suggest that this model and the extensions it engenders may provide value to climate prediction and uncertainty quantification.