Andrew C. Miller

Antoine Wehenkel, Laura Manduchi, Jens Behrmann et al. · apple-ml

Over the past decades, hemodynamics simulators have steadily evolved and have become tools of choice for studying cardiovascular systems in-silico. While such tools are routinely used to simulate whole-body hemodynamics from physiological parameters, solving the corresponding inverse problem of mapping waveforms back to plausible physiological parameters remains both promising and challenging. Motivated by advances in simulation-based inference (SBI), we cast this inverse problem as statistical inference. In contrast to alternative approaches, SBI provides \textit{posterior distributions} for the parameters of interest, providing a \textit{multi-dimensional} representation of uncertainty for \textit{individual} measurements. We showcase this ability by performing an in-silico uncertainty analysis of five biomarkers of clinical interest comparing several measurement modalities. Beyond the corroboration of known facts, such as the feasibility of estimating heart rate, our study highlights the potential of estimating new biomarkers from standard-of-care measurements. SBI reveals practically relevant findings that cannot be captured by standard sensitivity analyses, such as the existence of sub-populations for which parameter estimation exhibits distinct uncertainty regimes. Finally, we study the gap between in-vivo and in-silico with the MIMIC-III waveform database and critically discuss how cardiovascular simulations can inform real-world data analysis.

Luhuan Wu, Andrew Miller, Lauren Anderson et al.

We examine the general problem of inter-domain Gaussian Processes (GPs): problems where the GP realization and the noisy observations of that realization lie on different domains. When the mapping between those domains is linear, such as integration or differentiation, inference is still closed form. However, many of the scaling and approximation techniques that our community has developed do not apply to this setting. In this work, we introduce the hierarchical inducing point GP (HIP-GP), a scalable inter-domain GP inference method that enables us to improve the approximation accuracy by increasing the number of inducing points to the millions. HIP-GP, which relies on inducing points with grid structure and a stationary kernel assumption, is suitable for low-dimensional problems. In developing HIP-GP, we introduce (1) a fast whitening strategy, and (2) a novel preconditioner for conjugate gradients which can be helpful in general GP settings. Our code is available at https: //github.com/cunningham-lab/hipgp.

Salar Abbaspourazad, Oussama Elachqar, Andrew C. Miller et al.

Tracking biosignals is crucial for monitoring wellness and preempting the development of severe medical conditions. Today, wearable devices can conveniently record various biosignals, creating the opportunity to monitor health status without disruption to one's daily routine. Despite widespread use of wearable devices and existing digital biomarkers, the absence of curated data with annotated medical labels hinders the development of new biomarkers to measure common health conditions. In fact, medical datasets are usually small in comparison to other domains, which is an obstacle for developing neural network models for biosignals. To address this challenge, we have employed self-supervised learning using the unlabeled sensor data collected under informed consent from the large longitudinal Apple Heart and Movement Study (AHMS) to train foundation models for two common biosignals: photoplethysmography (PPG) and electrocardiogram (ECG) recorded on Apple Watch. We curated PPG and ECG datasets from AHMS that include data from ~141K participants spanning ~3 years. Our self-supervised learning framework includes participant level positive pair selection, stochastic augmentation module and a regularized contrastive loss optimized with momentum training, and generalizes well to both PPG and ECG modalities. We show that the pre-trained foundation models readily encode information regarding participants' demographics and health conditions. To the best of our knowledge, this is the first study that builds foundation models using large-scale PPG and ECG data collected via wearable consumer devices $\unicode{x2013}$ prior works have commonly used smaller-size datasets collected in clinical and experimental settings. We believe PPG and ECG foundation models can enhance future wearable devices by reducing the reliance on labeled data and hold the potential to help the users improve their health.

Jens Behrmann, Maria R. Cervera, Antoine Wehenkel et al.

Smart wearables enable continuous tracking of established biomarkers such as heart rate, heart rate variability, and blood oxygen saturation via photoplethysmography (PPG). Beyond these metrics, PPG waveforms contain richer physiological information, as recent deep learning (DL) studies demonstrate. However, DL models often rely on features with unclear physiological meaning, creating a tension between predictive power, clinical interpretability, and sensor design. We address this gap by introducing PPGen, a biophysical model that relates PPG signals to interpretable physiological and optical parameters. Building on PPGen, we propose hybrid amortized inference (HAI), enabling fast, robust, and scalable estimation of relevant physiological parameters from PPG signals while correcting for model misspecification. In extensive in-silico experiments, we show that HAI can accurately infer physiological parameters under diverse noise and sensor conditions. Our results illustrate a path toward PPG models that retain the fidelity needed for DL-based features while supporting clinical interpretation and informed hardware design.

Andrew C. Miller, Leon A. Gatys, Joseph Futoma et al.

Machine learning models $-$ now commonly developed to screen, diagnose, or predict health conditions $-$ are evaluated with a variety of performance metrics. An important first step in assessing the practical utility of a model is to evaluate its average performance over an entire population of interest. In many settings, it is also critical that the model makes good predictions within predefined subpopulations. For instance, showing that a model is fair or equitable requires evaluating the model's performance in different demographic subgroups. However, subpopulation performance metrics are typically computed using only data from that subgroup, resulting in higher variance estimates for smaller groups. We devise a procedure to measure subpopulation performance that can be more sample-efficient than the typical subsample estimates. We propose using an evaluation model $-$ a model that describes the conditional distribution of the predictive model score $-$ to form model-based metric (MBM) estimates. Our procedure incorporates model checking and validation, and we propose a computationally efficient approximation of the traditional nonparametric bootstrap to form confidence intervals. We evaluate MBMs on two main tasks: a semi-synthetic setting where ground truth metrics are available and a real-world hospital readmission prediction task. We find that MBMs consistently produce more accurate and lower variance estimates of model performance for small subpopulations.

Jeffrey Chan, Andrew C. Miller, Emily B. Fox

Modern wearable devices are embedded with a range of noninvasive biomarker sensors that hold promise for improving detection and treatment of disease. One such sensor is the single-lead electrocardiogram (ECG) which measures electrical signals in the heart. The benefits of the sheer volume of ECG measurements with rich longitudinal structure made possible by wearables come at the price of potentially noisier measurements compared to clinical ECGs, e.g., due to movement. In this work, we develop a statistical model to simulate a structured noise process in ECGs derived from a wearable sensor, design a beat-to-beat representation that is conducive for analyzing variation, and devise a factor analysis-based method to denoise the ECG. We study synthetic data generated using a realistic ECG simulator and a structured noise model. At varying levels of signal-to-noise, we quantitatively measure an upper bound on performance and compare estimates from linear and non-linear models. Finally, we apply our method to a set of ECGs collected by wearables in a mobile health study.

Andrew C. Miller, Nicholas J. Foti, Emily Fox

We develop a new model of insulin-glucose dynamics for forecasting blood glucose in type 1 diabetics. We augment an existing biomedical model by introducing time-varying dynamics driven by a machine learning sequence model. Our model maintains a physiologically plausible inductive bias and clinically interpretable parameters -- e.g., insulin sensitivity -- while inheriting the flexibility of modern pattern recognition algorithms. Critical to modeling success are the flexible, but structured representations of subject variability with a sequence model. In contrast, less constrained models like the LSTM fail to provide reliable or physiologically plausible forecasts. We conduct an extensive empirical study. We show that allowing biomedical model dynamics to vary in time improves forecasting at long time horizons, up to six hours, and produces forecasts consistent with the physiological effects of insulin and carbohydrates.

Andrew C. Miller, Ziad Obermeyer, Sendhil Mullainathan

Databases of electronic health records (EHRs) are increasingly used to inform clinical decisions. Machine learning methods can find patterns in EHRs that are predictive of future adverse outcomes. However, statistical models may be built upon patterns of health-seeking behavior that vary across patient subpopulations, leading to poor predictive performance when training on one patient population and predicting on another. This note proposes two tests to better measure and understand model generalization. We use these tests to compare models derived from two data sources: (i) historical medical records, and (ii) electrocardiogram (EKG) waveforms. In a predictive task, we show that EKG-based models can be more stable than EHR-based models across different patient populations.

Andrew C. Miller, Ziad Obermeyer, David M. Blei et al.

An electrocardiogram (EKG) is a common, non-invasive test that measures the electrical activity of a patient's heart. EKGs contain useful diagnostic information about patient health that may be absent from other electronic health record (EHR) data. As multi-dimensional waveforms, they could be modeled using generic machine learning tools, such as a linear factor model or a variational autoencoder. We take a different approach:~we specify a model that directly represents the underlying electrophysiology of the heart and the EKG measurement process. We apply our model to two datasets, including a sample of emergency department EKG reports with missing data. We show that our model can more accurately reconstruct missing data (measured by test reconstruction error) than a standard baseline when there is significant missing data. More broadly, this physiological representation of heart function may be useful in a variety of settings, including prediction, causal analysis, and discovery.

Jeffrey Regier, Andrew C. Miller, David Schlegel et al.

We present a new, fully generative model for constructing astronomical catalogs from optical telescope image sets. Each pixel intensity is treated as a random variable with parameters that depend on the latent properties of stars and galaxies. These latent properties are themselves modeled as random. We compare two procedures for posterior inference. One procedure is based on Markov chain Monte Carlo (MCMC) while the other is based on variational inference (VI). The MCMC procedure excels at quantifying uncertainty, while the VI procedure is 1000 times faster. On a supercomputer, the VI procedure efficiently uses 665,000 CPU cores to construct an astronomical catalog from 50 terabytes of images in 14.6 minutes, demonstrating the scaling characteristics necessary to construct catalogs for upcoming astronomical surveys.

Yoon Kim, Sam Wiseman, Andrew C. Miller et al.

Amortized variational inference (AVI) replaces instance-specific local inference with a global inference network. While AVI has enabled efficient training of deep generative models such as variational autoencoders (VAE), recent empirical work suggests that inference networks can produce suboptimal variational parameters. We propose a hybrid approach, to use AVI to initialize the variational parameters and run stochastic variational inference (SVI) to refine them. Crucially, the local SVI procedure is itself differentiable, so the inference network and generative model can be trained end-to-end with gradient-based optimization. This semi-amortized approach enables the use of rich generative models without experiencing the posterior-collapse phenomenon common in training VAEs for problems like text generation. Experiments show this approach outperforms strong autoregressive and variational baselines on standard text and image datasets.

Andrew C. Miller, Nicholas J. Foti, Alexander D'Amour et al.

Optimization with noisy gradients has become ubiquitous in statistics and machine learning. Reparameterization gradients, or gradient estimates computed via the "reparameterization trick," represent a class of noisy gradients often used in Monte Carlo variational inference (MCVI). However, when these gradient estimators are too noisy, the optimization procedure can be slow or fail to converge. One way to reduce noise is to use more samples for the gradient estimate, but this can be computationally expensive. Instead, we view the noisy gradient as a random variable, and form an inexpensive approximation of the generating procedure for the gradient sample. This approximation has high correlation with the noisy gradient by construction, making it a useful control variate for variance reduction. We demonstrate our approach on non-conjugate multi-level hierarchical models and a Bayesian neural net where we observed gradient variance reductions of multiple orders of magnitude (20-2,000x).

Andrew C. Miller, Nicholas Foti, Ryan P. Adams

We propose a black-box variational inference method to approximate intractable distributions with an increasingly rich approximating class. Our method, termed variational boosting, iteratively refines an existing variational approximation by solving a sequence of optimization problems, allowing the practitioner to trade computation time for accuracy. We show how to expand the variational approximating class by incorporating additional covariance structure and by introducing new components to form a mixture. We apply variational boosting to synthetic and real statistical models, and show that resulting posterior inferences compare favorably to existing posterior approximation algorithms in both accuracy and efficiency.

Scott W. Linderman, Andrew C. Miller, Ryan P. Adams et al.

Many natural systems, such as neurons firing in the brain or basketball teams traversing a court, give rise to time series data with complex, nonlinear dynamics. We can gain insight into these systems by decomposing the data into segments that are each explained by simpler dynamic units. Building on switching linear dynamical systems (SLDS), we present a new model class that not only discovers these dynamical units, but also explains how their switching behavior depends on observations or continuous latent states. These "recurrent" switching linear dynamical systems provide further insight by discovering the conditions under which each unit is deployed, something that traditional SLDS models fail to do. We leverage recent algorithmic advances in approximate inference to make Bayesian inference in these models easy, fast, and scalable.

Jeffrey Regier, Andrew Miller, Jon McAuliffe et al.

We present a new, fully generative model of optical telescope image sets, along with a variational procedure for inference. Each pixel intensity is treated as a Poisson random variable, with a rate parameter dependent on latent properties of stars and galaxies. Key latent properties are themselves random, with scientific prior distributions constructed from large ancillary data sets. We check our approach on synthetic images. We also run it on images from a major sky survey, where it exceeds the performance of the current state-of-the-art method for locating celestial bodies and measuring their colors.

Andrew Miller, Luke Bornn, Ryan Adams et al.

We develop a machine learning approach to represent and analyze the underlying spatial structure that governs shot selection among professional basketball players in the NBA. Typically, NBA players are discussed and compared in an heuristic, imprecise manner that relies on unmeasured intuitions about player behavior. This makes it difficult to draw comparisons between players and make accurate player specific predictions. Modeling shot attempt data as a point process, we create a low dimensional representation of offensive player types in the NBA. Using non-negative matrix factorization (NMF), an unsupervised dimensionality reduction technique, we show that a low-rank spatial decomposition summarizes the shooting habits of NBA players. The spatial representations discovered by the algorithm correspond to intuitive descriptions of NBA player types, and can be used to model other spatial effects, such as shooting accuracy.