arXiv subjects

Gabriel Loewinger

Publications and source records attributed to Gabriel Loewinger.

5 recordsLinked to original sources

arXiv2025

Fast Penalized Generalized Estimating Equations for Large Longitudinal Functional Datasets

Longitudinal binary or count functional data are common in neuroscience, but are often too large to analyze with existing functional regression methods. We propose one-step penalized generalized estimating equations that supports generalized functional outcomes (e.g., count, binary, proportion, continuous-valued) and is fast even when datasets have a large number of clusters and large cluster sizes. The method applies to functional and scalar covariates and the one-step estimation framework enables efficient smoothing parameter selection, bootstrapping, and joint confidence interval construction. Importantly, this semi-parametric approach yields coefficient confidence intervals that are provably valid asymptotically even under working correlation misspecification. By developing a general theory for adaptive one-step M-estimation, we prove that the coefficient estimates are asymptotically normal and as efficient as the fully-iterated estimator; we verify these theoretical properties in simulations. We illustrate the benefits of our approach for analyzing large-scale neural recordings by applying it to a recent calcium imaging dataset published in Nature. We show that our method reveals important timing effects obscured in non-functional analyses. In doing so, we also demonstrate scaling to common neuroscience dataset sizes: the one-step estimator fits to a dataset with 150,000 (binary) functional outcomes, each observed at 120 functional domain points, in only 6.5 minutes on a laptop without parallelization. We release our methods in the R package 'fastfGEE', which supports a wide range of link functions and working covariances.

stat.ME↗

arXiv2024

Nonparametric causal inference for optogenetics: sequential excursion effects for dynamic regimes

Optogenetics is a powerful neuroscience technique for studying how neural circuit manipulation affects behavior. Standard analysis conventions discard information and severely limit the scope of the causal questions that can be probed. To address this gap, we 1) draw connections to the causal inference literature on sequentially randomized experiments, 2) propose a non-parametric framework for analyzing "open-loop" (static regime) optogenetics behavioral experiments, 3) derive extensions of history-restricted marginal structural models for dynamic treatment regimes with positivity violations for "closed-loop" designs, and 4) propose a taxonomy of identifiable causal effects that encompass a far richer collection of scientific questions compared to standard methods. From another view, our work extends "excursion effect" methods, popularized recently in the mobile health literature, to enable estimation of causal contrasts for treatment sequences in the presence of positivity violations. We describe sufficient conditions for identifiability of the proposed causal estimands, and provide asymptotic statistical guarantees for a proposed inverse probability-weighted estimator, a multiply-robust estimator (for two intervention timepoints), a framework for hypothesis testing, and a computationally scalable implementation. Finally, we apply our framework to data from a recent neuroscience study and show how it provides insight into causal effects of optogenetics on behavior that are obscured by standard analyses.

stat.ME↗

arXiv2024

Reliability and predictability of phenotype information from functional connectivity in large imaging datasets

One of the central objectives of contemporary neuroimaging research is to create predictive models that can disentangle the connection between patterns of functional connectivity across the entire brain and various behavioral traits. Previous studies have shown that models trained to predict behavioral features from the individual's functional connectivity have modest to poor performance. In this study, we trained models that predict observable individual traits (phenotypes) and their corresponding singular value decomposition (SVD) representations - herein referred to as latent phenotypes from resting state functional connectivity. For this task, we predicted phenotypes in two large neuroimaging datasets: the Human Connectome Project (HCP) and the Philadelphia Neurodevelopmental Cohort (PNC). We illustrate the importance of regressing out confounds, which could significantly influence phenotype prediction. Our findings reveal that both phenotypes and their corresponding latent phenotypes yield similar predictive performance. Interestingly, only the first five latent phenotypes were reliably identified, and using just these reliable phenotypes for predicting phenotypes yielded a similar performance to using all latent phenotypes. This suggests that the predictable information is present in the first latent phenotypes, allowing the remainder to be filtered out without any harm in performance. This study sheds light on the intricate relationship between functional connectivity and the predictability and reliability of phenotypic information, with potential implications for enhancing predictive modeling in the realm of neuroimaging research.

q-bio.NC↗

arXiv2022

Multi-Task Learning for Sparsity Pattern Heterogeneity: Statistical and Computational Perspectives

We consider a problem in Multi-Task Learning (MTL) where multiple linear models are jointly trained on a collection of datasets ("tasks"). A key novelty of our framework is that it allows the sparsity pattern of regression coefficients and the values of non-zero coefficients to differ across tasks while still leveraging partially shared structure. Our methods encourage models to share information across tasks through separately encouraging 1) coefficient supports, and/or 2) nonzero coefficient values to be similar. This allows models to borrow strength during variable selection even when non-zero coefficient values differ across tasks. We propose a novel mixed-integer programming formulation for our estimator. We develop custom scalable algorithms based on block coordinate descent and combinatorial local search to obtain high-quality (approximate) solutions for our estimator. Additionally, we propose a novel exact optimization algorithm to obtain globally optimal solutions. We investigate the theoretical properties of our estimators. We formally show how our estimators leverage the shared support information across tasks to achieve better variable selection performance. We evaluate the performance of our methods in simulations and two biomedical applications. Our proposed approaches appear to outperform other sparse MTL methods in variable selection and prediction accuracy. We provide the sMTL package on CRAN.

stat.ME↗

arXiv2021

Optimal Ensemble Construction for Multi-Study Prediction with Applications to COVID-19 Excess Mortality Estimation

It is increasingly common to encounter prediction tasks in the biomedical sciences for which multiple datasets are available for model training. Common approaches such as pooling datasets and applying standard statistical learning methods can result in poor out-of-study prediction performance when datasets are heterogeneous. Theoretical and applied work has shown $\textit{multi-study ensembling}$ to be a viable alternative that leverages the variability across datasets in a manner that promotes model generalizability. Multi-study ensembling uses a two-stage $\textit{stacking}$ strategy which fits study-specific models and estimates ensemble weights separately. This approach ignores, however, the ensemble properties at the model-fitting stage, potentially resulting in a loss of efficiency. We therefore propose $\textit{optimal ensemble construction}$, an $\textit{all-in-one}$ approach to multi-study stacking whereby we jointly estimate ensemble weights as well as parameters associated with each study-specific model. We prove that limiting cases of our approach yield existing methods such as multi-study stacking and pooling datasets before model fitting. We propose an efficient block coordinate descent algorithm to optimize the proposed loss function. We compare our approach to standard methods by applying it to a multi-country COVID-19 dataset for baseline mortality prediction. We show that when little data is available for a country before the onset of the pandemic, leveraging data from other countries can substantially improve prediction accuracy. Importantly, our approach outperforms multi-study stacking and other standard methods in this application. We further characterize the method's performance in simulations. Our method remains competitive with or outperforms multi-study stacking and other earlier methods across a range of between-study heterogeneity levels.

stat.ML↗