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Bianca Dumitrascu

Publications and source records attributed to Bianca Dumitrascu.

13 recordsLinked to original sources

Variational Learning of Disentangled Representations

Disentangled representations separate factors that are shared across conditions from those that are condition-specific. Such separation is needed for generalization to new domains, treatments, patients, or species. A dominant line of work pursues this goal through variational formulations. While these approaches achieve partial disentanglement, they often exhibit three common limitations: they either do not remove all condition-specific information from the condition-specific representation, allow the condition-specific representation to become uninformative, or impose independence assumptions that do not reflect the underlying generative process. In this work, we introduce DisCoVR, a variational framework that addresses these limitations. Its objective is aligned with the probabilistic structure of the data-generating process, and includes an adversarial term that prevents condition-specific information from being encoded in the condition-specific representation.DisCoVR reconstructs the data from both shared and condition-specific representations, ensuring that each remains informative, and uses a structured prior that further reinforces the informativeness of both representations. We show that across synthetic, image, and single-cell RNA-sequencing datasets, DisCoVR achieves stronger disentanglement compared to previous approaches.

cs.LG

Goal-Oriented Influence-Maximizing Data Acquisition for Learning and Optimization

Active data acquisition is central to many learning and optimization tasks in deep neural networks, yet remains challenging because most approaches rely on predictive uncertainty estimates that are difficult to obtain reliably. To this end, we propose Goal-Oriented Influence- Maximizing Data Acquisition (GOIMDA), an active acquisition algorithm that avoids explicit posterior inference while remaining uncertainty-aware through inverse curvature. GOIMDA selects inputs by maximizing their expected influence on a user-specified goal functional, such as test loss, predictive entropy, or the value of an optimizer-recommended design. Leveraging first-order influence functions, we derive a tractable acquisition rule that combines the goal gradient, training-loss curvature, and candidate sensitivity to model parameters. We show theoretically that, for generalized linear models, GOIMDA approximates predictive-entropy minimization up to a correction term accounting for goal alignment and prediction bias, thereby, yielding uncertainty-aware behavior without maintaining a Bayesian posterior. Empirically, across learning tasks (including image and text classification) and optimization tasks (including noisy global optimization benchmarks and neural-network hyperparameter tuning), GOIMDA consistently reaches target performance with substantially fewer labeled samples or function evaluations than uncertainty-based active learning and Gaussian-process Bayesian optimization baselines.

stat.ML

Sequential Gaussian Processes for Online Learning of Nonstationary Functions

Many machine learning problems can be framed in the context of estimating functions, and often these are time-dependent functions that are estimated in real-time as observations arrive. Gaussian processes (GPs) are an attractive choice for modeling real-valued nonlinear functions due to their flexibility and uncertainty quantification. However, the typical GP regression model suffers from several drawbacks: 1) Conventional GP inference scales $O(N^{3})$ with respect to the number of observations; 2) Updating a GP model sequentially is not trivial; and 3) Covariance kernels typically enforce stationarity constraints on the function, while GPs with non-stationary covariance kernels are often intractable to use in practice. To overcome these issues, we propose a sequential Monte Carlo algorithm to fit infinite mixtures of GPs that capture non-stationary behavior while allowing for online, distributed inference. Our approach empirically improves performance over state-of-the-art methods for online GP estimation in the presence of non-stationarity in time-series data. To demonstrate the utility of our proposed online Gaussian process mixture-of-experts approach in applied settings, we show that we can sucessfully implement an optimization algorithm using online Gaussian process bandits.

stat.ML

Dimensionless machine learning: Imposing exact units equivariance

Units equivariance (or units covariance) is the exact symmetry that follows from the requirement that relationships among measured quantities of physics relevance must obey self-consistent dimensional scalings. Here, we express this symmetry in terms of a (non-compact) group action, and we employ dimensional analysis and ideas from equivariant machine learning to provide a methodology for exactly units-equivariant machine learning: For any given learning task, we first construct a dimensionless version of its inputs using classic results from dimensional analysis, and then perform inference in the dimensionless space. Our approach can be used to impose units equivariance across a broad range of machine learning methods which are equivariant to rotations and other groups. We discuss the in-sample and out-of-sample prediction accuracy gains one can obtain in contexts like symbolic regression and emulation, where symmetry is important. We illustrate our approach with simple numerical examples involving dynamical systems in physics and ecology.

stat.ML

MarkerMap: nonlinear marker selection for single-cell studies

Single-cell RNA-seq data allow the quantification of cell type differences across a growing set of biological contexts. However, pinpointing a small subset of genomic features explaining this variability can be ill-defined and computationally intractable. Here we introduce MarkerMap, a generative model for selecting minimal gene sets which are maximally informative of cell type origin and enable whole transcriptome reconstruction. MarkerMap provides a scalable framework for both supervised marker selection, aimed at identifying specific cell type populations, and unsupervised marker selection, aimed at gene expression imputation and reconstruction. We benchmark MarkerMap's competitive performance against previously published approaches on real single cell gene expression data sets. MarkerMap is available as a pip installable package, as a community resource aimed at developing explainable machine learning techniques for enhancing interpretability in single-cell studies.

stat.ML

Approximate Latent Force Model Inference

Physically-inspired latent force models offer an interpretable alternative to purely data driven tools for inference in dynamical systems. They carry the structure of differential equations and the flexibility of Gaussian processes, yielding interpretable parameters and dynamics-imposed latent functions. However, the existing inference techniques associated with these models rely on the exact computation of posterior kernel terms which are seldom available in analytical form. Most applications relevant to practitioners, such as Hill equations or diffusion equations, are hence intractable. In this paper, we overcome these computational problems by proposing a variational solution to a general class of non-linear and parabolic partial differential equation latent force models. Further, we show that a neural operator approach can scale our model to thousands of instances, enabling fast, distributed computation. We demonstrate the efficacy and flexibility of our framework by achieving competitive performance on several tasks where the kernels are of varying degrees of tractability.

cs.LG

Deep learning for bioimage analysis

Deep learning has transformed the way large and complex image datasets can be processed, reshaping what is possible in bioimage analysis. As the complexity and size of bioimage data continues to grow, this new analysis paradigm is becoming increasingly ubiquitous. In this Review, we begin by introducing the concepts needed for beginners to understand deep learning. We then review how deep learning has impacted bioimage analysis and explore the open-source resources available to integrate it into a research project. Finally, we discuss the future of deep learning applied to cell and developmental biology. We analyse how state-of-the-art methodologies have the potential to transform our understanding of biological systems through new image-based analysis and modelling that integrate multimodal inputs in space and time.

q-bio.QM

Nonparametric Bayesian multi-armed bandits for single cell experiment design

The problem of maximizing cell type discovery under budget constraints is a fundamental challenge for the collection and analysis of single-cell RNA-sequencing (scRNA-seq) data. In this paper, we introduce a simple, computationally efficient, and scalable Bayesian nonparametric sequential approach to optimize the budget allocation when designing a large scale experiment for the collection of scRNA-seq data for the purpose of, but not limited to, creating cell atlases. Our approach relies on the following tools: i) a hierarchical Pitman-Yor prior that recapitulates biological assumptions regarding cellular differentiation, and ii) a Thompson sampling multi-armed bandit strategy that balances exploitation and exploration to prioritize experiments across a sequence of trials. Posterior inference is performed by using a sequential Monte Carlo approach, which allows us to fully exploit the sequential nature of our species sampling problem. We empirically show that our approach outperforms state-of-the-art methods and achieves near-Oracle performance on simulated and scRNA-seq data alike. HPY-TS code is available at https://github.com/fedfer/HPYsinglecell.

stat.AP

Patient-Specific Effects of Medication Using Latent Force Models with Gaussian Processes

Multi-output Gaussian processes (GPs) are a flexible Bayesian nonparametric framework that has proven useful in jointly modeling the physiological states of patients in medical time series data. However, capturing the short-term effects of drugs and therapeutic interventions on patient physiological state remains challenging. We propose a novel approach that models the effect of interventions as a hybrid Gaussian process composed of a GP capturing patient physiology convolved with a latent force model capturing effects of treatments on specific physiological features. This convolution of a multi-output GP with a GP including a causal time-marked kernel leads to a well-characterized model of the patients' physiological state responding to interventions. We show that our model leads to analytically tractable cross-covariance functions, allowing scalable inference. Our hierarchical model includes estimates of patient-specific effects but allows sharing of support across patients. Our approach achieves competitive predictive performance on challenging hospital data, where we recover patient-specific response to the administration of three common drugs: one antihypertensive drug and two anticoagulants.

stat.ML

Sparse Multi-Output Gaussian Processes for Medical Time Series Prediction

In the scenario of real-time monitoring of hospital patients, high-quality inference of patients' health status using all information available from clinical covariates and lab tests is essential to enable successful medical interventions and improve patient outcomes. Developing a computational framework that can learn from observational large-scale electronic health records (EHRs) and make accurate real-time predictions is a critical step. In this work, we develop and explore a Bayesian nonparametric model based on Gaussian process (GP) regression for hospital patient monitoring. We propose MedGP, a statistical framework that incorporates 24 clinical and lab covariates and supports a rich reference data set from which relationships between observed covariates may be inferred and exploited for high-quality inference of patient state over time. To do this, we develop a highly structured sparse GP kernel to enable tractable computation over tens of thousands of time points while estimating correlations among clinical covariates, patients, and periodicity in patient observations. MedGP has a number of benefits over current methods, including (i) not requiring an alignment of the time series data, (ii) quantifying confidence regions in the predictions, (iii) exploiting a vast and rich database of patients, and (iv) inferring interpretable relationships among clinical covariates. We evaluate and compare results from MedGP on the task of online prediction for three patient subgroups from two medical data sets across 8,043 patients. We found MedGP improves online prediction over baseline methods for nearly all covariates across different disease subgroups and studies. The publicly available code is at https://github.com/bee-hive/MedGP.

stat.ML

PG-TS: Improved Thompson Sampling for Logistic Contextual Bandits

We address the problem of regret minimization in logistic contextual bandits, where a learner decides among sequential actions or arms given their respective contexts to maximize binary rewards. Using a fast inference procedure with Polya-Gamma distributed augmentation variables, we propose an improved version of Thompson Sampling, a Bayesian formulation of contextual bandits with near-optimal performance. Our approach, Polya-Gamma augmented Thompson Sampling (PG-TS), achieves state-of-the-art performance on simulated and real data. PG-TS explores the action space efficiently and exploits high-reward arms, quickly converging to solutions of low regret. Its explicit estimation of the posterior distribution of the context feature covariance leads to substantial empirical gains over approximate approaches. PG-TS is the first approach to demonstrate the benefits of Polya-Gamma augmentation in bandits and to propose an efficient Gibbs sampler for approximating the analytically unsolvable integral of logistic contextual bandits.

stat.ML

BIISQ: Bayesian nonparametric discovery of Isoforms and Individual Specific Quantification

Most human protein-coding genes can be transcribed into multiple possible distinct mRNA isoforms. These alternative splicing patterns encourage molecular diversity and dysregulation of isoform expression plays an important role in disease etiology. However, isoforms are difficult to characterize from short-read RNA-seq data because they share identical subsequences and exist in tissue- and sample-specific frequencies. Here, we develop BIISQ, a Bayesian nonparametric model to discover Isoforms and Individual Specific Quantification from RNA-seq data. BIISQ does not require known isoform reference sequences but instead estimates isoform composition directly with an isoform catalog shared across samples. We develop a stochastic variational inference approach for efficient and robust posterior inference and demonstrate superior precision and recall for short read RNA-seq simulations and simulated short read data from PacBio long read sequencing when compared to state-of-the-art isoform reconstruction methods. BIISQ achieves the most significant gains for longer (in terms of exons) isoforms and isoforms that are lowly expressed (over 500% more transcripts correctly inferred at low coverage in simulations). Finally, we estimate isoforms in the GEUVADIS RNA-seq data, identify genetic variants that regulate transcript ratios, and demonstrate variant enrichment in functional elements related to mRNA splicing regulation.

q-bio.QM

A Bayesian test to identify variance effects

Identifying genetic variants that regulate quantitative traits, or QTLs, is the primary focus of the field of statistical genetics. Most current methods are limited to identifying mean effects, or associations between genotype and the mean value of a quantitative trait. It is possible, however, that a genetic variant may affect the variance of the quantitative trait in lieu of, or in addition to, affecting the trait mean. Here, we develop a general methodological approach to identifying covariates with variance effects on a quantitative trait using a Bayesian heteroskedastic linear regression model. We show that our Bayesian test for heteroskedasticity (BTH) outperforms classical tests for differences in variation across a large range of simulations drawn from scenarios common to the analysis of quantitative traits. We apply BTH to methylation QTL study data and expression QTL study data to identify variance QTLs. When compared with three tests for heteroskedasticity used in genomics, we illustrate the benefits of using our approach, including avoiding overfitting by incorporating uncertainty and flexibly identifying heteroskedastic effects.

q-bio.QM