arXiv subjects

Peter Carbonetto

Publications and source records attributed to Peter Carbonetto.

16 recordsLinked to original sources

arXiv2026

Non-negative matrix factorization algorithms generally improve topic model fits

In an effort to develop topic modeling methods that can be quickly applied to large data sets, we revisit the problem of maximum-likelihood estimation in topic models. It is known, at least informally, that maximum-likelihood estimation in topic models is closely related to non-negative matrix factorization (NMF). Yet, to our knowledge, this relationship has not been exploited previously to fit topic models. We show that recent advances in NMF optimization methods can be leveraged to fit topic models very efficiently, often resulting in much better fits and in less time than existing algorithms for topic models. We also formally make the connection between the NMF optimization problem and maximum-likelihood estimation for the topic model, and using this result we show that the expectation maximization (EM) algorithm for the topic model is essentially the same as the classic multiplicative updates for NMF (the only difference being that the operations are performed in a different order). Our methods are implemented in the R package fastTopics.

stat.ML↗

arXiv2026

Empirical Bayes Shrinkage of Functional Effects, with Application to Analysis of Dynamic eQTLs

We introduce functional adaptive shrinkage (FASH), an empirical Bayes method for joint analysis of observation units in which each unit estimates an effect function at several values of a continuous condition variable. The ideas in this paper are motivated by dynamic expression quantitative trait locus (eQTL) studies, which aim to characterize how genetic effects on gene expression vary with time or another continuous condition. FASH integrates a broad family of Gaussian processes defined through linear differential operators into an empirical Bayes shrinkage framework, enabling adaptive smoothing and borrowing of information across units. This provides improved estimation of effect functions and principled hypothesis testing, allowing straightforward computation of significance measures such as local false discovery and false sign rates. To encourage conservative inferences, we propose a simple prior- adjustment method that has theoretical guarantees and can be more broadly used with other empirical Bayes methods. We illustrate the benefits of FASH by reanalyzing dynamic eQTL data on cardiomyocyte differentiation from induced pluripotent stem cells. FASH identified novel dynamic eQTLs, revealed diverse temporal effect patterns, and provided improved power compared with the original analysis. More broadly, FASH offers a flexible statistical framework for joint analysis of functional data, with applications extending beyond genomics. To facilitate use of FASH in dynamic eQTL studies and other settings, we provide an accompanying R package at https: //github.com/stephenslab/fashr.

stat.ME↗

arXiv2026

A New Family of Poisson Non-negative Matrix Factorization Methods Using the Shifted Log Link

Poisson non-negative matrix factorization (NMF) is a widely used method to find interpretable "parts-based" decompositions of count data. While many variants of Poisson NMF exist, existing methods assume that the "parts" in the decomposition combine additively. This assumption may be natural in some settings, but not in others. Here we introduce Poisson NMF with the shifted-log link function to relax this assumption. The shifted-log link function has a single tuning parameter, and as this parameter varies the model changes from assuming that parts combine additively (i.e., standard Poisson NMF) to assuming that parts combine more multiplicatively. We provide an algorithm to fit this model by maximum likelihood, and also an approximation that substantially reduces computation time for large, sparse datasets (computations scale with the number of non-zero entries in the data matrix). We illustrate these new methods on a variety of real datasets. Our examples show how the choice of link function in Poisson NMF can substantively impact the results, and how in some settings the use of a shifted-log link function may improve interpretability compared with the standard, additive link.

cs.LG↗

arXiv2025

Covariate-moderated Empirical Bayes Matrix Factorization

Matrix factorization is a fundamental method in statistics and machine learning for inferring and summarizing structure in multivariate data. Modern data sets often come with "side information" of various forms (images, text, graphs) that can be leveraged to improve estimation of the underlying structure. However, existing methods that leverage side information are limited in the types of data they can incorporate, and they assume specific parametric models. Here, we introduce a novel method for this problem, covariate-moderated empirical Bayes matrix factorization (cEBMF). cEBMF is a modular framework that accepts any type of side information that is processable by a probabilistic model or a neural network. The cEBMF framework can accommodate different assumptions and constraints on the factors through the use of different priors, and it adapts these priors to the data. We demonstrate the benefits of cEBMF in simulations and in analyses of spatial transcriptomics and collaborative filtering data. A PyTorch-based implementation of cEBMF with flexible priors is available at https://github.com/william-denault/cebmf_torch.

stat.ME↗

arXiv2025

Bayesian variable selection in a Cox proportional hazards model with the "Sum of Single Effects" prior

Motivated by genetic fine-mapping applications, we introduce a new approach to Bayesian variable selection regression (BVSR) for time-to-event (TTE) outcomes. This new approach is designed to deal with the specific challenges that arise in genetic fine-mapping, including: the presence of very strong correlations among the covariates, often exceeding 0.99; very large data sets containing potentially thousands of covariates and hundreds of thousands of samples. We accomplish this by extending the "Sum of Single Effects" (SuSiE) method to the Cox proportional hazards (CoxPH) model. We demonstrate the benefits of the new method, "CoxPH-SuSiE", over existing BVSR methods for TTE outcomes in simulated fine-mapping data sets. We also illustrate CoxPH-SuSiE on real data by fine-mapping asthma loci using data from UK Biobank. This fine-mapping identified 14 asthma risk SNPs in 8 asthma risk loci, among which 6 had strong evidence for being causal (posterior inclusion probability greater than 50%). Two of the 6 putatively causal variants are known to be pathogenic, and others lie within a genomic sequence that is known to regulate the expression of GATA3.

stat.ME↗

arXiv2024

Gradient-based optimization for variational empirical Bayes multiple regression

Variational empirical Bayes (VEB) methods provide a practically attractive approach to fitting large, sparse, multiple regression models. These methods usually use coordinate ascent to optimize the variational objective function, an approach known as coordinate ascent variational inference (CAVI). Here we propose alternative optimization approaches based on gradient-based (quasi-Newton) methods, which we call gradient-based variational inference (GradVI). GradVI exploits a recent result from Kim et. al. [arXiv:2208.10910] which writes the VEB regression objective function as a penalized regression. Unfortunately the penalty function is not available in closed form, and we present and compare two approaches to dealing with this problem. In simple situations where CAVI performs well, we show that GradVI produces similar predictive performance, and GradVI converges in fewer iterations when the predictors are highly correlated. Furthermore, unlike CAVI, the key computations in GradVI are simple matrix-vector products, and so GradVI is much faster than CAVI in settings where the design matrix admits fast matrix-vector products (e.g., as we show here, trendfiltering applications) and lends itself to parallelized implementations in ways that CAVI does not. GradVI is also very flexible, and could exploit automatic differentiation to easily implement different prior families. Our methods are implemented in an open-source Python software, GradVI (available from https://github.com/stephenslab/gradvi ).

stat.ME↗

arXiv2024

Improved methods for empirical Bayes multivariate multiple testing and effect size estimation

Estimating the sharing of genetic effects across different conditions is important to many statistical analyses of genomic data. The patterns of sharing arising from these data are often highly heterogeneous. To flexibly model these heterogeneous sharing patterns, Urbut et al. (2019) proposed the multivariate adaptive shrinkage (MASH) method to jointly analyze genetic effects across multiple conditions. However, multivariate analyses using MASH (as well as other multivariate analyses) require good estimates of the sharing patterns, and estimating these patterns efficiently and accurately remains challenging. Here we describe new empirical Bayes methods that provide improvements in speed and accuracy over existing methods. The two key ideas are: (1) adaptive regularization to improve accuracy in settings with many conditions; (2) improving the speed of the model fitting algorithms by exploiting analytical results on covariance estimation. In simulations, we show that the new methods provide better model fits, better out-of-sample performance, and improved power and accuracy in detecting the true underlying signals. In an analysis of eQTLs in 49 human tissues, our new analysis pipeline achieves better model fits and better out-of-sample performance than the existing MASH analysis pipeline. We have implemented the new methods, which we call ``Ultimate Deconvolution'', in an R package, udr, available on GitHub.

stat.ME↗

arXiv2024

A flexible empirical Bayes approach to multiple linear regression and connections with penalized regression

We introduce a new empirical Bayes approach for large-scale multiple linear regression. Our approach combines two key ideas: (i) the use of flexible "adaptive shrinkage" priors, which approximate the nonparametric family of scale mixture of normal distributions by a finite mixture of normal distributions; and (ii) the use of variational approximations to efficiently estimate prior hyperparameters and compute approximate posteriors. Combining these two ideas results in fast and flexible methods, with computational speed comparable to fast penalized regression methods such as the Lasso, and with competitive prediction accuracy across a wide range of scenarios. Further, we provide new results that establish conceptual connections between our empirical Bayes methods and penalized methods. Specifically, we show that the posterior mean from our method solves a penalized regression problem, with the form of the penalty function being learned from the data by directly solving an optimization problem (rather than being tuned by cross-validation). Our methods are implemented in an R package, mr.ash.alpha, available from https://github.com/stephenslab/mr.ash.alpha.

stat.ME↗

arXiv2024

A flexible model for correlated count data, with application to multi-condition differential expression analyses of single-cell RNA sequencing data

Detecting differences in gene expression is an important part of single-cell RNA sequencing experiments, and many statistical methods have been developed for this aim. Most differential expression analyses focus on comparing expression between two groups (e.g., treatment vs. control). But there is increasing interest in multi-condition differential expression analyses in which expression is measured in many conditions, and the aim is to accurately detect and estimate expression differences in all conditions. We show that directly modeling single-cell RNA-seq counts in all conditions simultaneously, while also inferring how expression differences are shared across conditions, leads to greatly improved performance for detecting and estimating expression differences compared to existing methods. We illustrate the potential of this new approach by analyzing data from a single-cell experiment studying the effects of cytokine stimulation on gene expression. We call our new method "Poisson multivariate adaptive shrinkage", and it is implemented in an R package available online at https://github.com/stephenslab/poisson.mash.alpha.

stat.ME↗

arXiv2024

ebnm: An R Package for Solving the Empirical Bayes Normal Means Problem Using a Variety of Prior Families

The empirical Bayes normal means (EBNM) model is important to many areas of statistics, including (but not limited to) multiple testing, wavelet denoising, and gene expression analysis. There are several existing software packages that can fit EBNM models under different prior assumptions and using different algorithms; however, the differences across interfaces complicate direct comparisons. Further, a number of important prior assumptions do not yet have implementations. Motivated by these issues, we developed the R package ebnm, which provides a unified interface for efficiently fitting EBNM models using a variety of prior assumptions, including nonparametric approaches. In some cases, we incorporated existing implementations into ebnm; in others, we implemented new fitting procedures with a focus on speed and numerical stability. We illustrate the use of ebnm in a detailed analysis of baseball statistics. By providing a unified and easily extensible interface, the ebnm package can facilitate development of new methods in statistics, genetics, and other areas; as an example, we briefly discuss the R package flashier, which harnesses methods in ebnm to provide a flexible and robust approach to matrix factorization.

stat.CO↗

arXiv2020

A fast algorithm for maximum likelihood estimation of mixture proportions using sequential quadratic programming

Maximum likelihood estimation of mixture proportions has a long history, and continues to play an important role in modern statistics, including in development of nonparametric empirical Bayes methods. Maximum likelihood of mixture proportions has traditionally been solved using the expectation maximization (EM) algorithm, but recent work by Koenker & Mizera shows that modern convex optimization techniques -- in particular, interior point methods -- are substantially faster and more accurate than EM. Here, we develop a new solution based on sequential quadratic programming (SQP). It is substantially faster than the interior point method, and just as accurate. Our approach combines several ideas: first, it solves a reformulation of the original problem; second, it uses an SQP approach to make the best use of the expensive gradient and Hessian computations; third, the SQP iterations are implemented using an active set method to exploit the sparse nature of the quadratic subproblems; fourth, it uses accurate low-rank approximations for more efficient gradient and Hessian computations. We illustrate the benefits of our approach in experiments on synthetic data sets as well as a large genetic association data set. In large data sets (n = 1,000,000 observations, m = 1,000 mixture components), our implementation achieves at least 100-fold reduction in runtime compared with a state-of-the-art interior point solver. Our methods are implemented in Julia, and in an R package available on CRAN (see https://CRAN.R-project.org/package=mixsqp).

stat.CO↗

arXiv2020

Flexible signal denoising via flexible empirical Bayes shrinkage

Signal denoising---also known as non-parametric regression---is often performed through shrinkage estimation in a transformed (e.g., wavelet) domain; shrinkage in the transformed domain corresponds to smoothing in the original domain. A key question in such applications is how much to shrink, or, equivalently, how much to smooth. Empirical Bayes shrinkage methods provide an attractive solution to this problem; they use the data to estimate a distribution of underlying "effects", hence automatically select an appropriate amount of shrinkage. However, most existing implementations of Empirical Bayes shrinkage are less flexible than they could be--both in their assumptions on the underlying distribution of effects, and in their ability to handle heterskedasticity---which limits their signal denoising applications. Here we address this by taking a particularly flexible, stable and computationally convenient Empirical Bayes shrinkage method, and we apply it to several signal denoising problems. These applications include smoothing of Poisson data and heteroskedastic Gaussian data. We show through empirical comparisons that the results are competitive with other methods, including both simple thresholding rules and purpose-built Empirical Bayes procedures. Our methods are implemented in the R package smashr, "SMoothing by Adaptive SHrinkage in R," available at https://www.github.com/stephenslab/smashr

stat.ME↗

arXiv2017

varbvs: Fast Variable Selection for Large-scale Regression

We introduce varbvs, a suite of functions written in R and MATLAB for regression analysis of large-scale data sets using Bayesian variable selection methods. We have developed numerical optimization algorithms based on variational approximation methods that make it feasible to apply Bayesian variable selection to very large data sets. With a focus on examples from genome-wide association studies, we demonstrate that varbvs scales well to data sets with hundreds of thousands of variables and thousands of samples, and has features that facilitate rapid data analyses. Moreover, varbvs allows for extensive model customization, which can be used to incorporate external information into the analysis. We expect that the combination of an easy-to-use interface and robust, scalable algorithms for posterior computation will encourage broader use of Bayesian variable selection in areas of applied statistics and computational biology. The most recent R and MATLAB source code is available for download at Github (https://github.com/pcarbo/varbvs), and the R package can be installed from CRAN (https://cran.r-project.org/package=varbvs).

stat.CO↗

arXiv2012

Polygenic Modeling with Bayesian Sparse Linear Mixed Models

Both linear mixed models (LMMs) and sparse regression models are widely used in genetics applications, including, recently, polygenic modeling in genome-wide association studies. These two approaches make very different assumptions, so are expected to perform well in different situations. However, in practice, for a given data set one typically does not know which assumptions will be more accurate. Motivated by this, we consider a hybrid of the two, which we refer to as a "Bayesian sparse linear mixed model" (BSLMM) that includes both these models as special cases. We address several key computational and statistical issues that arise when applying BSLMM, including appropriate prior specification for the hyper-parameters, and a novel Markov chain Monte Carlo algorithm for posterior inference. We apply BSLMM and compare it with other methods for two polygenic modeling applications: estimating the proportion of variance in phenotypes explained (PVE) by available genotypes, and phenotype (or breeding value) prediction. For PVE estimation, we demonstrate that BSLMM combines the advantages of both standard LMMs and sparse regression modeling. For phenotype prediction it considerably outperforms either of the other two methods, as well as several other large-scale regression methods previously suggested for this problem. Software implementing our method is freely available from http://stephenslab.uchicago.edu/software.html

q-bio.QM↗

arXiv2012

Integrated analysis of variants and pathways in genome-wide association studies using polygenic models of disease

Many common diseases are highly polygenic, modulated by a large number genetic factors with small effects on susceptibility to disease. These small effects are difficult to map reliably in genetic association studies. To address this problem, researchers have developed methods that aggregate information over sets of related genes, such as biological pathways, to identify gene sets that are enriched for genetic variants associated with disease. However, these methods fail to answer a key question: which genes and genetic variants are associated with disease risk? We develop a method based on sparse multiple regression that simultaneously identifies enriched pathways, and prioritizes the variants within these pathways, to locate additional variants associated with disease susceptibility. A central feature of our approach is an estimate of the strength of enrichment, which yields a coherent way to prioritize variants in enriched pathways. We illustrate the benefits of our approach in a genome-wide association study of Crohn's disease with ~440,000 genetic variants genotyped for ~4700 study subjects. We obtain strong support for enrichment of IL-12, IL-23 and other cytokine signaling pathways. Furthermore, prioritizing variants in these enriched pathways yields support for additional disease-association variants, all of which have been independently reported in other case-control studies for Crohn's disease.

q-bio.QM↗

arXiv2012

Nonparametric Bayesian Logic

The Bayesian Logic (BLOG) language was recently developed for defining first-order probability models over worlds with unknown numbers of objects. It handles important problems in AI, including data association and population estimation. This paper extends BLOG by adopting generative processes over function spaces - known as nonparametrics in the Bayesian literature. We introduce syntax for reasoning about arbitrary collections of objects, and their properties, in an intuitive manner. By exploiting exchangeability, distributions over unknown objects and their attributes are cast as Dirichlet processes, which resolve difficulties in model selection and inference caused by varying numbers of objects. We demonstrate these concepts with application to citation matching.

cs.AI↗