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Celia M. T. Greenwood

Publications and source records attributed to Celia M. T. Greenwood.

7 recordsLinked to original sources

Maximum Tsallis Entropy Distributions for Robust and Efficient Sparse Learning from Correlated Data

This paper addresses the limitations of Gaussian distribution assumptions in statistical sparse learning, particularly in modeling correlated and heterogeneous data. Conventional Gaussian models often lack robustness towards outliers and underlying distribution assumptions. To overcome these limitations, we propose the use of the $q$Gaussian distribution, derived from Tsallis entropy maximization, as a robust alternative. This is notably relevant in biostatistics, where the presence of correlated observations and heterogeneity, such as in genetic and longitudinal studies, is prevalent. Our contributions include modeling of correlated data through the re-derived multivariate probability density function from Tsallis entropy maximization, thereby addressing the limitations inherent in conventional Gaussian models. Furthermore, we introduce a novel framework that adapts numerical methods designed to find equilibria in flows to tackle composite optimization problems prevalent in statistical sparse learning. Applying this framework to the Hager-Zhang conjugate gradient algorithm \cite{Hager2005}, we develop a numerically stable and efficient algorithm for sparse statistical learning. The $q$Gaussian distribution, informed by the principle of maximizing Tsallis entropy, presents a viable and flexible alternative to Gaussian-based methods. This paper not only contributes to the theoretical understanding of statistical distributions and optimization techniques, but also paves the way for practical data analysis.

math.OC↗

Varying-coefficient mixture of experts model for dynamic heterogeneous populations: application to mouse cortical development

As cells differentiate, gene-gene associations may change. Because the composition of cell subtypes also shifts with development, it is challenging to establish whether those changes reflect real changes in gene regulation within one or more subpopulations or a spurious one due to the shifting composition. Only formal inference can separate them. We propose a Varying-Coefficient Mixture-of-Experts (VCMoE) model in which the coefficients of both the gating functions and the expert components vary smoothly with the index variable, so that a subgroup-specific association can be inferred without being confounded by the concurrent shift in subgroup composition. We develop a label-consistent EM algorithm and establish the identifiability and asymptotic theory that make the resulting inference valid. These guarantees support simultaneous confidence bands, constructed using asymptotic and bootstrap methods, together with a generalized likelihood ratio test for constant coefficient functions. Simulations demonstrate accurate estimation and satisfactory coverage. Applied to single-nucleus RNA-sequencing data from embryonic mouse cortex, VCMoE finds that the repression of Bcl11b by Satb2 within the upper layer is not yet in place when those neurons first appear and becomes established over the course of differentiation, a dynamic that an ordinary mixture-of-experts model neglected. A package for implementing the method is available.

stat.ME↗

Multivariate regression with missing response data for modelling regional DNA methylation QTLs

Identifying genetic regulators of DNA methylation (mQTLs) with multivariate models enhances statistical power, but is challenged by missing data from bisulfite sequencing. Standard imputation-based methods can introduce bias, limiting reliable inference. We propose \texttt{missoNet}, a novel convex estimation framework that jointly estimates regression coefficients and the precision matrix from data with missing responses. By using unbiased surrogate estimators, our three-stage procedure avoids imputation while simultaneously performing variable selection and learning the conditional dependence structure among responses. We establish theoretical error bounds, and our simulations demonstrate that \texttt{missoNet} consistently outperforms existing methods in both prediction and sparsity recovery. In a real-world mQTL analysis of the CARTaGENE cohort, \texttt{missoNet} achieved superior predictive accuracy and false-discovery control on a held-out validation set, identifying known and credible novel genetic associations. The method offers a robust, efficient, and theoretically grounded tool for genomic analyses, and is available as an R package.

stat.ME↗

fastHDMI: Fast Mutual Information Estimation for High-Dimensional Data

In this paper, we introduce fastHDMI, a Python package designed for efficient variable screening in high-dimensional datasets, particularly neuroimaging data. This work pioneers the application of three mutual information estimation methods for neuroimaging variable selection, a novel approach implemented via fastHDMI. These advancements enhance our ability to analyze the complex structures of neuroimaging datasets, providing improved tools for variable selection in high-dimensional spaces. Using the preprocessed ABIDE dataset, we evaluate the performance of these methods through extensive simulations. The tests cover a range of conditions, including linear and nonlinear associations, as well as continuous and binary outcomes. Our results highlight the superiority of the FFTKDE-based mutual information estimation for feature screening in continuous nonlinear outcomes, while binning-based methods outperform others for binary outcomes with nonlinear probability preimages. For linear simulations, both Pearson correlation and FFTKDE-based methods show comparable performance for continuous outcomes, while Pearson excels in binary outcomes with linear probability preimages. A comprehensive case study using the ABIDE dataset further demonstrates fastHDMI's practical utility, showcasing the predictive power of models built from variables selected using our screening techniques. This research affirms the computational efficiency and methodological strength of fastHDMI, significantly enriching the toolkit available for neuroimaging analysis.

stat.ML↗

An algorithm-based multiple detection influence measure for high dimensional regression using expectile

The identification of influential observations is an important part of data analysis that can prevent erroneous conclusions drawn from biased estimators. However, in high dimensional data, this identification is challenging. Classical and recently-developed methods often perform poorly when there are multiple influential observations in the same dataset. In particular, current methods can fail when there is masking several influential observations with similar characteristics, or swamping when the influential observations are near the boundary of the space spanned by well-behaved observations. Therefore, we propose an algorithm-based, multi-step, multiple detection procedure to identify influential observations that addresses current limitations. Our three-step algorithm to identify and capture undesirable variability in the data, $\asymMIP,$ is based on two complementary statistics, inspired by asymmetric correlations, and built on expectiles. Simulations demonstrate higher detection power than competing methods. Use of the resulting asymptotic distribution leads to detection of influential observations without the need for computationally demanding procedures such as the bootstrap. The application of our method to the Autism Brain Imaging Data Exchange neuroimaging dataset resulted in a more balanced and accurate prediction of brain maturity based on cortical thickness. See our GitHub for a free R package that implements our algorithm: \texttt{asymMIP} (\url{github.com/AmBarry/hidetify}).

stat.ME↗

Detecting differentially methylated regions in bisulfite sequencing data using quasi-binomial mixed models with smooth covariate effect estimates

Identifying disease-associated changes in DNA methylation can help to gain a better understanding of disease etiology. Bisulfite sequencing technology allows the generation of methylation profiles at single base of DNA. We previously developed a method for estimating smooth covariate effects and identifying differentially methylated regions (DMRs) from bisulfite sequencing data, which copes with experimental errors and variable read depths; this method utilizes the binomial distribution to characterize the variability in the methylated counts. However, bisulfite sequencing data frequently include low-count integers and can exhibit over or under dispersion relative to the binomial distribution. We present a substantial improvement to our previous work by proposing a quasi-likelihood-based regional testing approach which accounts for multiplicative and additive sources of dispersion. We demonstrate the theoretical properties of the resulting tests, as well as their marginal and conditional interpretations. Simulations show that the proposed method provides correct inference for smooth covariate effects and captures the major methylation patterns with excellent power.

stat.ME↗

Alternating optimization for GxE modelling with weighted genetic and environmental scores: examples from the MAVAN study

Motivated by the goal of expanding currently existing genotype x environment interaction (GxE) models to simultaneously include multiple genetic variants and environmental exposures in a parsimonious way, we developed a novel method to estimate the parameters in a GxE model, where G is a weighted sum of genetic variants (genetic score) and E is a weighted sum of environments (environmental score). The approach uses alternating optimization to estimate the parameters of the GxE model. This is an iterative process where the genetic score weights, the environmental score weights, and the main model parameters are estimated in turn assuming the other parameters to be constant. This technique can be used to construct relatively complex interaction models that are constrained to a particular structure, and hence contain fewer parameters. We present the model as a two-way interaction longitudinal mixed model, for which ordinary linear regression is a special case, but it can easily be extended to be compatible with k-way interaction models and generalized linear mixed models. The model is implemented in R (LEGIT package) and using SAS macros (LEGIT_SAS). Here we present examples from the Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study where we improve significantly upon already existing models using alternating optimization. Furthermore, through simulations, we demonstrate the power and validity of this approach even with small sample sizes.

stat.AP↗