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Akihiko Nishimura

Publications and source records attributed to Akihiko Nishimura.

At least 19 recordsLinked to original sources
arXiv2026

Spectral Collapsed Gibbs Sampler for Bayesian Sparse Regression

Sparse regression based on global-local shrinkage priors are increasingly used for Bayesian modeling of modern high-dimensional data, but scaling up the Gibbs sampler for posterior inference remains a challenge. While much effort has gone into speeding up the high-dimensional coefficient update step, insufficient attention has been given to the potential poor mixing of the global scale parameter $τ$ and of the overall sampler. One proposed remedy has been to marginalize out the coefficients when updating $τ$. Here we show that, while this collapsed update was previously thought to require a Metropolis step, we can in fact sample directly and efficiently from the collapsed density. This is made possible by careful linear algebraic manipulations and a strategic per-Gibbs-scan spectral decomposition, allowing subsequent evaluations of the collapsed density across hundreds of values of $τ$ at negligible cost. We combine this computational trick with adaptive numerical integration and inverse transform sampling to construct a direct sampler. This eliminates the need to tune Metropolis proposals and yields faster convergence and improved mixing. We demonstrate our method on two big data applications, fitting logistic regression under the horseshoe prior to datasets with design matrices of size 120,000 x 1,379 and 1,980 x 17,848.

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arXiv2026

Constructing Genetic Risk Scores: Robust Bayesian Approach through Projected Summary Statistics and Flexible Shrinkage

Polygenic risk scores (PRS) developed from genome-wide association studies (GWAS) can be used for risk stratification by quantifying the genetic contribution to disease, and many clinical applications have been proposed. Bayesian methods are popular for building PRS because of their natural ability to regularize models and incorporate external information. In this article, we present new theoretical results, methods, and extensive numerical studies to advance Bayesian methods for PRS applications. We identify a potential risk, under a common Bayesian PRS framework, of posterior impropriety when integrating the required GWAS summary statistics and linkage disequilibrium (LD) data from distinct sources. As a principled remedy, we propose a projection of the summary statistics that ensures compatibility between the two sources and in turn a proper behavior of the posterior. We further introduce a new PRS method, with accompanying software, under the less-explored Bayesian bridge prior to more flexibly model varying sparsity levels in effect-size distributions. We extensively benchmark it against alternative Bayesian methods using synthetic and real datasets, quantifying the impact of prior specification and LD estimation strategy. Our proposed PRS-Bridge, equipped with the projection technique and flexible prior, demonstrates the most consistent and generally superior performance across a variety of scenarios.

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arXiv2026

MCMC using $\textit{bouncy}$ Hamiltonian dynamics: A unifying framework for Hamiltonian Monte Carlo and piecewise deterministic Markov process samplers

Piecewise-deterministic Markov process (PDMP) samplers constitute a state-of-the-art Markov chain Monte Carlo paradigm in Bayesian computation, with examples including the zig-zag and bouncy particle sampler (bps). Recent work on the zig-zag has indicated its connection to Hamiltonian Monte Carlo (HMC), a version of the Metropolis algorithm that exploits Hamiltonian dynamics. Here we establish that, in fact, the connection between the two paradigms extends far beyond the specific instance. The key lies in (1) the fact that any time-reversible deterministic dynamics provides a valid Metropolis proposal and (2) how PDMPs' characteristic velocity changes constitute an alternative to the usual acceptance-rejection. We turn this observation into a rigorous framework for constructing rejection-free Metropolis proposals based on bouncy Hamiltonian dynamics which simultaneously possess Hamiltonian-like properties and generate discontinuous trajectories similar in appearance to PDMPs. When combined with periodic refreshment of the inertia, the dynamics converge strongly to PDMP equivalents in the limit of increasingly frequent refreshment. We demonstrate the practical implications of this new framework with a sampler based on a bouncy Hamiltonian dynamics closely related to the bps. The resulting sampler exhibits competitive performance on challenging real-data posteriors involving tens of thousands of parameters. As the sampler of choice in modern probabilistic programming languages, HMC plays a critical role in applied Bayesian modeling; by generalizing the paradigm and elucidating its connection to the leading competitor, our framework opens up opportunities for cross-pollination and innovation to further scale Bayesian inference.

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arXiv2026

Smoothing Out Sticking Points: Sampling from Discrete-Continuous Mixtures with Dynamical Monte Carlo by Mapping Discrete Mass into a Latent Universe

Combining a continuous "slab" density with discrete "spike" mass at zero, spike-and-slab priors provide important tools for inducing sparsity and carrying out variable selection in Bayesian models. However, the presence of discrete mass makes posterior inference challenging. "Sticky" extensions to piecewise-deterministic Markov process samplers have shown promising performance, where sampling from the spike is achieved by the process sticking there for an exponentially distributed duration. As it turns out, the sampler remains valid when the exponential sticking time is replaced with its expectation. We justify this by mapping the spike to a continuous density over a latent universe, allowing the sampler to be reinterpreted as traversing this universe while being stuck in the original space. This perspective opens up an array of possibilities to carry out posterior computation under spike-and-slab type priors. Notably, it enables us to construct sticky samplers using other dynamics-based paradigms such as Hamiltonian Monte Carlo; in fact, original sticky process can be established as a partial position-momentum refreshment limit of our Hamiltonian sticky sampler. Our theoretical and empirical findings suggest these alternatives to be at least as efficient as the original sticky approach.

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arXiv2025

Bayesian shape-constrained regression for quantifying Alzheimer's disease biomarker progression

Several biomarkers are hypothesized to indicate early stages of Alzheimer's disease, well before the cognitive symptoms manifest. Their precise relations to the disease progression, however, is poorly understood. This lack of understanding limits our ability to diagnose the disease and intervene effectively at early stages. To provide better understanding of the relation between the disease and biomarker progressions, we propose a novel modeling approach to quantify the biomarkers' trajectories as functions of age. Building on monotone regression splines, we introduce two additional shape constraints to incorporate structures informed by the current medical literature. First, we impose the regression curves to satisfy a vanishing derivative condition, reflecting the observation that changes in biomarkers generally plateau at early and late stages of the disease. Second, we enforce the regression curves to have a unique inflection point, which enhances interpretability of the estimated disease progression and facilitates assessment of temporal ordering among the biomarkers. We fit our shape-constrained regression model under Bayesian framework to take advantage of its ability to account for the heterogeneity in disease progression among individuals. When applied to the BIOCARD data, the model is able to capture asymmetry in the biomarkers' progressions while maintaining interpretability, yielding estimates of the curves with temporal ordering consistent with the existing scientific hypotheses.

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arXiv2024

Zigzag path connects two Monte Carlo samplers: Hamiltonian counterpart to a piecewise deterministic Markov process

Zigzag and other piecewise deterministic Markov process samplers have attracted significant interest for their non-reversibility and other appealing properties for Bayesian posterior computation. Hamiltonian Monte Carlo is another state-of-the-art sampler, exploiting fictitious momentum to guide Markov chains through complex target distributions. We establish an important connection between the zigzag sampler and a variant of Hamiltonian Monte Carlo based on Laplace-distributed momentum. The position and velocity component of the corresponding Hamiltonian dynamics travels along a zigzag path paralleling the Markovian zigzag process; however, the dynamics is non-Markovian in this position-velocity space as the momentum component encodes non-immediate pasts. This information is partially lost during a momentum refreshment step, in which we preserve its direction but re-sample magnitude. In the limit of increasingly frequent momentum refreshments, we prove that Hamiltonian zigzag converges strongly to its Markovian counterpart. This theoretical insight suggests that, when retaining full momentum information, Hamiltonian zigzag can better explore target distributions with highly correlated parameters by suppressing the diffusive behavior of Markovian zigzag. We corroborate this intuition by comparing performance of the two zigzag cousins on high-dimensional truncated multivariate Gaussians, including a 11,235-dimensional target arising from a Bayesian phylogenetic multivariate probit modeling of HIV virus data.

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arXiv2023

Commentary on Guyll et al. (2023): Misuse of Statistical Method Results in Highly Biased Interpretation of Forensic Evidence

Since the National Academy of Sciences released their report outlining paths for improving reliability, standards, and policies in the forensic sciences NAS (2009), there has been heightened interest in evaluating and improving the scientific validity within forensic science disciplines. Guyll et al. (2023) seek to evaluate the validity of forensic cartridge-case comparisons. However, they make a serious statistical error that leads to highly inflated claims about the probability that a cartridge case from a crime scene was fired from a reference gun, typically a gun found in the possession of a defendant. It is urgent to address this error since these claims, which are generally biased against defendants, are being presented by the prosecution in an ongoing homicide case where the defendant faces the possibility of a lengthy prison sentence (DC Superior Court, 2023).

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arXiv2023

Bayesian Safety Surveillance with Adaptive Bias Correction

Post-market safety surveillance is an integral part of mass vaccination programs. Typically relying on sequential analysis of real-world health data as they accrue, safety surveillance is challenged by the difficulty of sequential multiple testing and by biases induced by residual confounding. The current standard approach based on the maximized sequential probability ratio test (MaxSPRT) fails to satisfactorily address these practical challenges and it remains a rigid framework that requires pre-specification of the surveillance schedule. We develop an alternative Bayesian surveillance procedure that addresses both challenges using a more flexible framework. We adopt a joint statistical modeling approach to sequentially estimate the effect of vaccine exposure on the adverse event of interest and correct for estimation bias by simultaneously analyzing a large set of negative control outcomes through a Bayesian hierarchical model. We then compute a posterior probability of the alternative hypothesis via Markov chain Monte Carlo sampling and use it for sequential detection of safety signals. Through an empirical evaluation using six US observational healthcare databases covering more than 360 million patients, we benchmark the proposed procedure against MaxSPRT on testing errors and estimation accuracy, under two epidemiological designs, the historical comparator and the self-controlled case series. We demonstrate that our procedure substantially reduces Type 1 error rates, maintains high statistical power, delivers fast signal detection, and provides considerably more accurate estimation. As an effort to promote open science, we present all empirical results in an R ShinyApp and provide full implementation of our method in the R package EvidenceSynthesis.

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arXiv2022

hdtg: An R package for high-dimensional truncated normal simulation

Simulating from the multivariate truncated normal distribution (MTN) is required in various statistical applications yet remains challenging in high dimensions. Currently available algorithms and their implementations often fail when the number of parameters exceeds a few hundred. To provide a general computational tool to efficiently sample from high-dimensional MTNs, we introduce the hdtg package that implements two state-of-the-art simulation algorithms: harmonic Hamiltonian Monte Carlo (harmonic-HMC) and zigzag Hamiltonian Monte Carlo (Zigzag-HMC). Both algorithms exploit analytical solutions of the Hamiltonian dynamics under a quadratic potential energy with hard boundary constraints, leading to rejection-free methods. We compare their efficiencies against another state-of-the-art algorithm for MTN simulation, the minimax tilting accept-reject sampler (MET). The run-time of these three approaches heavily depends on the underlying multivariate normal correlation structure. Zigzag-HMC and harmonic-HMC both achieve 100 effective samples within 3,600 seconds across all tests with dimension ranging from 100 to 1,600, while MET has difficulty in several high-dimensional examples. We provide guidance on how to choose an appropriate method for a given situation and illustrate the usage of hdtg.

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arXiv2022

Accelerating Bayesian inference of dependency between complex biological traits

Inferring dependencies between complex biological traits while accounting for evolutionary relationships between specimens is of great scientific interest yet remains infeasible when trait and specimen counts grow large. The state-of-the-art approach uses a phylogenetic multivariate probit model to accommodate binary and continuous traits via a latent variable framework, and utilizes an efficient bouncy particle sampler (BPS) to tackle the computational bottleneck -- integrating many latent variables from a high-dimensional truncated normal distribution. This approach breaks down as the number of specimens grows and fails to reliably characterize conditional dependencies between traits. Here, we propose an inference pipeline for phylogenetic probit models that greatly outperforms BPS. The novelty lies in 1) a combination of the recent Zigzag Hamiltonian Monte Carlo (Zigzag-HMC) with linear-time gradient evaluations and 2) a joint sampling scheme for highly correlated latent variables and correlation matrix elements. In an application exploring HIV-1 evolution from 535 viruses, the inference requires joint sampling from an 11,235-dimensional truncated normal and a 24-dimensional covariance matrix. Our method yields a 5-fold speedup compared to BPS and makes it possible to learn partial correlations between candidate viral mutations and virulence. Computational speedup now enables us to tackle even larger problems: we study the evolution of influenza H1N1 glycosylations on around 900 viruses. For broader applicability, we extend the phylogenetic probit model to incorporate categorical traits, and demonstrate its use to study Aquilegia flower and pollinator co-evolution.

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arXiv2022

Adjusting for both sequential testing and systematic error in safety surveillance using observational data: Empirical calibration and MaxSPRT

Post-approval safety surveillance of medical products using observational healthcare data can help identify safety issues beyond those found in pre-approval trials. When testing sequentially as data accrue, maximum sequential probability ratio testing (MaxSPRT) is a common approach to maintaining nominal type 1 error. However, the true type 1 error may still deviate from the specified one because of systematic error due to the observational nature of the analysis. This systematic error may persist even after controlling for known confounders. Here we propose to address this issue by combing MaxSPRT with empirical calibration. In empirical calibration, we assume uncertainty about the systematic error in our analysis, the source of uncertainty commonly overlooked in practice. We infer a probability distribution of systematic error by relying on a large set of negative controls: exposure-outcome where no causal effect is believed to exist. Integrating this distribution into our test statistics has previously been shown to restore type 1 error to nominal. Here we show how we can calibrate the critical value central to MaxSPRT. We evaluate this novel approach using simulations and real electronic health records, using H1N1 vaccinations during the 2009-2010 season as an example. Results show that combining empirical calibration with MaxSPRT restores nominal type 1 error. In our real-world example, adjusting for systematic error using empirical calibration has a larger impact than, and hence is just as essential as, adjusting for sequential testing using MaxSPRT. We recommend performing both, using the method described here.

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arXiv2022

Computational Statistics and Data Science in the Twenty-first Century

Data science has arrived, and computational statistics is its engine. As the scale and complexity of scientific and industrial data grow, the discipline of computational statistics assumes an increasingly central role among the statistical sciences. An explosion in the range of real-world applications means the development of more and more specialized computational methods, but five Core Challenges remain. We provide a high-level introduction to computational statistics by focusing on its central challenges, present recent model-specific advances and preach the ever-increasing role of non-sequential computational paradigms such as multi-core, many-core and quantum computing. Data science is bringing major changes to computational statistics, and these changes will shape the trajectory of the discipline in the 21st century.

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arXiv2022

Learning and Predicting from Dynamic Models for COVID-19 Patient Monitoring

COVID-19 has challenged health systems to learn how to learn. This paper describes the context, methods and challenges for learning to improve COVID-19 care at one academic health center. Challenges to learning include: (1) choosing a right clinical target; (2) designing methods for accurate predictions by borrowing strength from prior patients' experiences; (3) communicating the methodology to clinicians so they understand and trust it; (4) communicating the predictions to the patient at the moment of clinical decision; and (5) continuously evaluating and revising the methods so they adapt to changing patients and clinical demands. To illustrate these challenges, this paper contrasts two statistical modeling approaches - prospective longitudinal models in common use and retrospective analogues complementary in the COVID-19 context - for predicting future biomarker trajectories and major clinical events. The methods are applied to and validated on a cohort of 1,678 patients who were hospitalized with COVID-19 during the early months of the pandemic. We emphasize graphical tools to promote physician learning and inform clinical decision making.

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arXiv2022

Prior-preconditioned conjugate gradient method for accelerated Gibbs sampling in "large $n$ & large $p$" Bayesian sparse regression

In a modern observational study based on healthcare databases, the number of observations and of predictors typically range in the order of $10^5$ ~ $10^6$ and of $10^4$ ~ $10^5$. Despite the large sample size, data rarely provide sufficient information to reliably estimate such a large number of parameters. Sparse regression techniques provide potential solutions, one notable approach being the Bayesian methods based on shrinkage priors. In the "large n & large p" setting, however, posterior computation encounters a major bottleneck at repeated sampling from a high-dimensional Gaussian distribution, whose precision matrix $Φ$ is expensive to compute and factorize. In this article, we present a novel algorithm to speed up this bottleneck based on the following observation: we can cheaply generate a random vector $b$ such that the solution to the linear system $Φβ= b$ has the desired Gaussian distribution. We can then solve the linear system by the conjugate gradient (CG) algorithm through matrix-vector multiplications by $Φ$; this involves no explicit factorization or calculation of $Φ$ itself. Rapid convergence of CG in this context is guaranteed by the theory of prior-preconditioning we develop. We apply our algorithm to a clinically relevant large-scale observational study with n = 72,489 patients and p = 22,175 clinical covariates, designed to assess the relative risk of adverse events from two alternative blood anti-coagulants. Our algorithm demonstrates an order of magnitude speed-up in posterior inference, in our case cutting the computation time from two weeks to less than a day.

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arXiv2021

Shrinkage with shrunken shoulders: Gibbs sampling shrinkage model posteriors with guaranteed convergence rates

Use of continuous shrinkage priors -- with a "spike" near zero and heavy-tails towards infinity -- is an increasingly popular approach to induce sparsity in parameter estimates. When the parameters are only weakly identified by the likelihood, however, the posterior may end up with tails as heavy as the prior, jeopardizing robustness of inference. A natural solution is to "shrink the shoulders" of a shrinkage prior by lightening up its tails beyond a reasonable parameter range, yielding a regularized version of the prior. We develop a regularization approach which, unlike previous proposals, preserves computationally attractive structures of original shrinkage priors. We study theoretical properties of the Gibbs sampler on resulting posterior distributions, with emphasis on convergence rates of the P{ó}lya-Gamma Gibbs sampler for sparse logistic regression. Our analysis shows that the proposed regularization leads to geometric ergodicity under a broad range of global-local shrinkage priors. Essentially, the only requirement is for the prior $π_{\rm local}$ on the local scale $λ$ to satisfy $π_{\rm local}(0) < \infty$. If $π_{\rm local}(\cdot)$ further satisfies $\lim_{λ\to 0} π_{\rm local}(λ) / λ^a < \infty$ for $a > 0$, as in the case of Bayesian bridge priors, we show the sampler to be uniformly ergodic.

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arXiv2021

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($α_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $α_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

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arXiv2021

Shrinkage-based random local clocks with scalable inference

Local clock models propose that the rate of molecular evolution is constant within phylogenetic sub-trees. Current local clock inference procedures scale poorly to large taxa problems, impose model misspecification, or require a priori knowledge of the existence and location of clocks. To overcome these challenges, we present an autocorrelated, Bayesian model of heritable clock rate evolution that leverages heavy-tailed priors with mean zero to shrink increments of change between branch-specific clocks. We further develop an efficient Hamiltonian Monte Carlo sampler that exploits closed form gradient computations to scale our model to large trees. Inference under our shrinkage-clock exhibits an over 3-fold speed increase compared to the popular random local clock when estimating branch-specific clock rates on a simulated dataset. We further show our shrinkage-clock recovers known local clocks within a rodent and mammalian phylogeny. Finally, in a problem that once appeared computationally impractical, we investigate the heritable clock structure of various surface glycoproteins of influenza A virus in the absence of prior knowledge about clock placement.

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arXiv2020

Large-scale inference of correlation among mixed-type biological traits with phylogenetic multivariate probit models

Inferring concerted changes among biological traits along an evolutionary history remains an important yet challenging problem. Besides adjusting for spurious correlation induced from the shared history, the task also requires sufficient flexibility and computational efficiency to incorporate multiple continuous and discrete traits as data size increases. To accomplish this, we jointly model mixed-type traits by assuming latent parameters for binary outcome dimensions at the tips of an unknown tree informed by molecular sequences. This gives rise to a phylogenetic multivariate probit model. With large sample sizes, posterior computation under this model is problematic, as it requires repeated sampling from a high-dimensional truncated normal distribution. Current best practices employ multiple-try rejection sampling that suffers from slow-mixing and a computational cost that scales quadratically in sample size. We develop a new inference approach that exploits 1) the bouncy particle sampler (BPS) based on piecewise deterministic Markov processes to simultaneously sample all truncated normal dimensions, and 2) novel dynamic programming that reduces the cost of likelihood and gradient evaluations for BPS to linear in sample size. In an application with 535 HIV viruses and 24 traits that necessitates sampling from a 12,840-dimensional truncated normal, our method makes it possible to estimate the across-trait correlation and detect factors that affect the pathogen's capacity to cause disease. This inference framework is also applicable to a broader class of covariance structures beyond comparative biology.

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