Annals of Applied Statistics最新文献

Phylodynamics is a set of population genetics tools that aim at reconstructing demographic history of a population based on molecular sequences of individuals sampled from the population of interest. One important task in phylodynamics is to estimate changes in (effective) population size. When applied to infectious disease sequences such estimation of population size trajectories can provide information about changes in the number of infections. To model changes in the number of infected individuals, current phylodynamic methods use non-parametric approaches (e.g., Bayesian curve-fitting based on change-point models or Gaussian process priors), parametric approaches (e.g., based on differential equations), and stochastic modeling in conjunction with likelihood-free Bayesian methods. The first class of methods yields results that are hard to interpret epidemiologically. The second class of methods provides estimates of important epidemiological parameters, such as infection and removal/recovery rates, but ignores variation in the dynamics of infectious disease spread. The third class of methods is the most advantageous statistically, but relies on computationally intensive particle filtering techniques that limits its applications. We propose a Bayesian model that combines phylodynamic inference and stochastic epidemic models, and achieves computational tractability by using a linear noise approximation (LNA) - a technique that allows us to approximate probability densities of stochastic epidemic model trajectories. LNA opens the door for using modern Markov chain Monte Carlo tools to approximate the joint posterior distribution of the disease transmission parameters and of high dimensional vectors describing unobserved changes in the stochastic epidemic model compartment sizes (e.g., numbers of infectious and susceptible individuals). In a simulation study, we show that our method can successfully recover parameters of stochastic epidemic models. We apply our estimation technique to Ebola genealogies estimated using viral genetic data from the 2014 epidemic in Sierra Leone and Liberia.

Accurate HIV incidence estimation based on individual recent infection status (recent vs long-term infection) is important for monitoring the epidemic, targeting interventions to those at greatest risk of new infection, and evaluating existing programs of prevention and treatment. Starting from 2015, the Population-based HIV Impact Assessment (PHIA) individual-level surveys are implemented in the most-affected countries in sub-Saharan Africa. PHIA is a nationally-representative HIV-focused survey that combines household visits with key questions and cutting-edge technologies such as biomarker tests for HIV antibody and HIV viral load which offer the unique opportunity of distinguishing between recent infection and long-term infection, and providing relevant HIV information by age, gender, and location. In this article, we propose a semi-supervised logistic regression model for estimating individual level HIV recency status. It incorporates information from multiple data sources - the PHIA survey where the true HIV recency status is unknown, and the cohort studies provided in the literature where the relationship between HIV recency status and the covariates are presented in the form of a contingency table. It also utilizes the national level HIV incidence estimates from the epidemiology model. Applying the proposed model to Malawi PHIA data, we demonstrate that our approach is more accurate for the individual level estimation and more appropriate for estimating HIV recency rates at aggregated levels than the current practice - the binary classification tree (BCT).

We propose the "study strap ensemble", which combines advantages of two common approaches to fitting prediction models when multiple training datasets ("studies") are available: pooling studies and fitting one model versus averaging predictions from multiple models each fit to individual studies. The study strap ensemble fits models to bootstrapped datasets, or "pseudo-studies." These are generated by resampling from multiple studies with a hierarchical resampling scheme that generalizes the randomized cluster bootstrap. The study strap is controlled by a tuning parameter that determines the proportion of observations to draw from each study. When the parameter is set to its lowest value, each pseudo-study is resampled from only a single study. When it is high, the study strap ignores the multi-study structure and generates pseudo-studies by merging the datasets and drawing observations like a standard bootstrap. We empirically show the optimal tuning value often lies in between, and prove that special cases of the study strap draw the merged dataset and the set of original studies as pseudo-studies. We extend the study strap approach with an ensemble weighting scheme that utilizes information in the distribution of the covariates of the test dataset. Our work is motivated by neuroscience experiments using real-time neurochemical sensing during awake behavior in humans. Current techniques to perform this kind of research require measurements from an electrode placed in the brain during awake neurosurgery and rely on prediction models to estimate neurotransmitter concentrations from the electrical measurements recorded by the electrode. These models are trained by combining multiple datasets that are collected in vitro under heterogeneous conditions in order to promote accuracy of the models when applied to data collected in the brain. A prevailing challenge is deciding how to combine studies or ensemble models trained on different studies to enhance model generalizability. Our methods produce marked improvements in simulations and in this application. All methods are available in the studyStrap CRAN package.

Wildland fire smoke contains hazardous levels of fine particulate matter (PM_2.5), a pollutant shown to adversely effect health. Estimating fire attributable PM_2.5 concentrations is key to quantifying the impact on air quality and subsequent health burden. This is a challenging problem since only total PM_2.5 is measured at monitoring stations and both fire-attributable PM_2.5 and PM_2.5 from all other sources are correlated in space and time. We propose a framework for estimating fire-contributed PM_2.5 and PM_2.5 from all other sources using a novel causal inference framework and bias-adjusted chemical model representations of PM_2.5 under counterfactual scenarios. The chemical model representation of PM_2.5 for this analysis is simulated using Community Multiscale Air Quality Modeling System (CMAQ), run with and without fire emissions across the contiguous U.S. for the 2008-2012 wildfire seasons. The CMAQ output is calibrated with observations from monitoring sites for the same spatial domain and time period. We use a Bayesian model that accounts for spatial variation to estimate the effect of wildland fires on PM_2.5 and state assumptions under which the estimate has a valid causal interpretation. Our results include estimates of the contributions of wildfire smoke to PM_2.5 for the contiguous U.S. Additionally, we compute the health burden associated with the PM_2.5 attributable to wildfire smoke.

Understanding sub-cellular protein localisation is an essential component in the analysis of context specific protein function. Recent advances in quantitative mass-spectrometry (MS) have led to high resolution mapping of thousands of proteins to sub-cellular locations within the cell. Novel modelling considerations to capture the complex nature of these data are thus necessary. We approach analysis of spatial proteomics data in a non-parametric Bayesian framework, using K-component mixtures of Gaussian process regression models. The Gaussian process regression model accounts for correlation structure within a sub-cellular niche, with each mixture component capturing the distinct correlation structure observed within each niche. The availability of marker proteins (i.e. proteins with a priori known labelled locations) motivates a semi-supervised learning approach to inform the Gaussian process hyperparameters. We moreover provide an efficient Hamiltonian-within-Gibbs sampler for our model. Furthermore, we reduce the computational burden associated with inversion of covariance matrices by exploiting the structure in the covariance matrix. A tensor decomposition of our covariance matrices allows extended Trench and Durbin algorithms to be applied to reduce the computational complexity of inversion and hence accelerate computation. We provide detailed case-studies on Drosophila embryos and mouse pluripotent embryonic stem cells to illustrate the benefit of semi-supervised functional Bayesian modelling of the data.

Neuroimaging studies have a growing interest in learning the association between the individual brain connectivity networks and their clinical characteristics. It is also of great interest to identify the sub brain networks as biomarkers to predict the clinical symptoms, such as disease status, potentially providing insight on neuropathology. This motivates the need for developing a new type of regression model where the response variable is scalar, and predictors are networks that are typically represented as adjacent matrices or weighted adjacent matrices, to which we refer as scalar-on-network regression. In this work, we develop a new boosting method for model fitting with sub-network markers selection. Our approach, as opposed to group lasso or other existing regularization methods, is essentially a gradient descent algorithm leveraging known network structure. We demonstrate the utility of our methods via simulation studies and analysis of the resting-state fMRI data in a cognitive developmental cohort study.

Identifying differences in networks has become a canonical problem in many biological applications. Existing methods try to accomplish this goal by either directly comparing the estimated structures of two networks, or testing the null hypothesis that the covariance or inverse covariance matrices in two populations are identical. However, estimation approaches do not provide measures of uncertainty, e.g., p-values, whereas existing testing approaches could lead to misleading results, as we illustrate in this paper. To address these shortcomings, we propose a qualitative hypothesis testing framework, which tests whether the connectivity structures in the two networks are the same. our framework is especially appropriate if the goal is to identify nodes or edges that are differentially connected. No existing approach could test such hypotheses and provide corresponding measures of uncertainty. Theoretically, we show that under appropriate conditions, our proposal correctly controls the type-I error rate in testing the qualitative hypothesis. Empirically, we demonstrate the performance of our proposal using simulation studies and applications in cancer genomics.

We propose a curve-free random-effects meta-analysis approach to combining data from multiple phase I clinical trials to identify an optimal dose. Our method accounts for between-study heterogeneity that may stem from different study designs, patient populations, or tumor types. We also develop a meta-analytic-predictive (MAP) method based on a power prior that incorporates data from multiple historical studies into the design and conduct of a new phase I trial. Performances of the proposed methods for data analysis and trial design are evaluated by extensive simulation studies. The proposed random-effects meta-analysis method provides more reliable dose selection than comparators that rely on parametric assumptions. The MAP-based dose-finding designs are generally more efficient than those that do not borrow information, especially when the current and historical studies are similar. The proposed methodologies are illustrated by a meta-analysis of five historical phase I studies of Sorafenib, and design of a new phase I trial.

Neuroradiologists and neurosurgeons increasingly opt to use functional magnetic resonance imaging (fMRI) to map functionally relevant brain regions for noninvasive presurgical planning and intraoperative neuronavigation. This application requires a high degree of spatial accuracy, but the fMRI signal-to-noise ratio (SNR) decreases as spatial resolution increases. In practice, fMRI scans can be collected at multiple spatial resolutions, and it is of interest to make more accurate inference on brain activity by combining data with different resolutions. To this end, we develop a new Bayesian model to leverage both better anatomical precision in high resolution fMRI and higher SNR in standard resolution fMRI. We assign a Gaussian process prior to the mean intensity function and develop an efficient, scalable posterior computation algorithm to integrate both sources of data. We draw posterior samples using an algorithm analogous to Riemann manifold Hamiltonian Monte Carlo in an expanded parameter space. We illustrate our method in analysis of presurgical fMRI data, and show in simulation that it infers the mean intensity more accurately than alternatives that use either the high or standard resolution fMRI data alone.

Reliably learning group structures among nodes in network data is challenging in several applications. We are particularly motivated by studying covert networks that encode relationships among criminals. These data are subject to measurement errors, and exhibit a complex combination of an unknown number of core-periphery, assortative and disassortative structures that may unveil key architectures of the criminal organization. The coexistence of these noisy block patterns limits the reliability of routinely-used community detection algorithms, and requires extensions of model-based solutions to realistically characterize the node partition process, incorporate information from node attributes, and provide improved strategies for estimation and uncertainty quantification. To cover these gaps, we develop a new class of extended stochastic block models (esbm) that infer groups of nodes having common connectivity patterns via Gibbs-type priors on the partition process. This choice encompasses many realistic priors for criminal networks, covering solutions with fixed, random and infinite number of possible groups, and facilitates the inclusion of node attributes in a principled manner. Among the new alternatives in our class, we focus on the Gnedin process as a realistic prior that allows the number of groups to be finite, random and subject to a reinforcement process coherent with criminal networks. A collapsed Gibbs sampler is proposed for the whole esbm class, and refined strategies for estimation, prediction, uncertainty quantification and model selection are outlined. The esbm performance is illustrated in realistic simulations and in an application to an Italian mafia network, where we unveil key complex block structures, mostly hidden from state-of-the-art alternatives.