arXiv subjects

José Miguel Hernández-Lobato

Publications and source records attributed to José Miguel Hernández-Lobato.

At least 55 records · Page 3Linked to original sources

arXiv2025

No Trick, No Treat: Pursuits and Challenges Towards Simulation-free Training of Neural Samplers

We consider the sampling problem, where the aim is to draw samples from a distribution whose density is known only up to a normalization constant. Recent breakthroughs in generative modeling to approximate a high-dimensional data distribution have sparked significant interest in developing neural network-based methods for this challenging problem. However, neural samplers typically incur heavy computational overhead due to simulating trajectories during training. This motivates the pursuit of simulation-free training procedures of neural samplers. In this work, we propose an elegant modification to previous methods, which allows simulation-free training with the help of a time-dependent normalizing flow. However, it ultimately suffers from severe mode collapse. On closer inspection, we find that nearly all successful neural samplers rely on Langevin preconditioning to avoid mode collapsing. We systematically analyze several popular methods with various objective functions and demonstrate that, in the absence of Langevin preconditioning, most of them fail to adequately cover even a simple target. Finally, we draw attention to a strong baseline by combining the state-of-the-art MCMC method, Parallel Tempering (PT), with an additional generative model to shed light on future explorations of neural samplers.

cs.LG↗

arXiv2025

Training Neural Samplers with Reverse Diffusive KL Divergence

Training generative models to sample from unnormalized density functions is an important and challenging task in machine learning. Traditional training methods often rely on the reverse Kullback-Leibler (KL) divergence due to its tractability. However, the mode-seeking behavior of reverse KL hinders effective approximation of multi-modal target distributions. To address this, we propose to minimize the reverse KL along diffusion trajectories of both model and target densities. We refer to this objective as the reverse diffusive KL divergence, which allows the model to capture multiple modes. Leveraging this objective, we train neural samplers that can efficiently generate samples from the target distribution in one step. We demonstrate that our method enhances sampling performance across various Boltzmann distributions, including both synthetic multi-modal densities and n-body particle systems.

cs.LG↗

arXiv2025

Nonparametric Heterogeneous Long-term Causal Effect Estimation via Data Combination

Long-term causal inference has drawn increasing attention in many scientific domains. Existing methods mainly focus on estimating average long-term causal effects by combining long-term observational data and short-term experimental data. However, it is still understudied how to robustly and effectively estimate heterogeneous long-term causal effects, significantly limiting practical applications. In this paper, we propose several two-stage style nonparametric estimators for heterogeneous long-term causal effect estimation, including propensity-based, regression-based, and multiple robust estimators. We conduct a comprehensive theoretical analysis of their asymptotic properties under mild assumptions, with the ultimate goal of building a better understanding of the conditions under which some estimators can be expected to perform better. Extensive experiments across several semi-synthetic and real-world datasets validate the theoretical results and demonstrate the effectiveness of the proposed estimators.

cs.LG↗

arXiv2025

Improving Linear System Solvers for Hyperparameter Optimisation in Iterative Gaussian Processes

Scaling hyperparameter optimisation to very large datasets remains an open problem in the Gaussian process community. This paper focuses on iterative methods, which use linear system solvers, like conjugate gradients, alternating projections or stochastic gradient descent, to construct an estimate of the marginal likelihood gradient. We discuss three key improvements which are applicable across solvers: (i) a pathwise gradient estimator, which reduces the required number of solver iterations and amortises the computational cost of making predictions, (ii) warm starting linear system solvers with the solution from the previous step, which leads to faster solver convergence at the cost of negligible bias, (iii) early stopping linear system solvers after a limited computational budget, which synergises with warm starting, allowing solver progress to accumulate over multiple marginal likelihood steps. These techniques provide speed-ups of up to $72\times$ when solving to tolerance, and decrease the average residual norm by up to $7\times$ when stopping early.

cs.LG↗

arXiv2024

A Generative Model of Symmetry Transformations

Correctly capturing the symmetry transformations of data can lead to efficient models with strong generalization capabilities, though methods incorporating symmetries often require prior knowledge. While recent advancements have been made in learning those symmetries directly from the dataset, most of this work has focused on the discriminative setting. In this paper, we take inspiration from group theoretic ideas to construct a generative model that explicitly aims to capture the data's approximate symmetries. This results in a model that, given a prespecified but broad set of possible symmetries, learns to what extent, if at all, those symmetries are actually present. Our model can be seen as a generative process for data augmentation. We provide a simple algorithm for learning our generative model and empirically demonstrate its ability to capture symmetries under affine and color transformations, in an interpretable way. Combining our symmetry model with standard generative models results in higher marginal test-log-likelihoods and improved data efficiency.

cs.LG↗

arXiv2024

Generative Model for Synthesizing Ionizable Lipids: A Monte Carlo Tree Search Approach

Ionizable lipids are essential in developing lipid nanoparticles (LNPs) for effective messenger RNA (mRNA) delivery. While traditional methods for designing new ionizable lipids are typically time-consuming, deep generative models have emerged as a powerful solution, significantly accelerating the molecular discovery process. However, a practical challenge arises as the molecular structures generated can often be difficult or infeasible to synthesize. This project explores Monte Carlo tree search (MCTS)-based generative models for synthesizable ionizable lipids. Leveraging a synthetically accessible lipid building block dataset and two specialized predictors to guide the search through chemical space, we introduce a policy network guided MCTS generative model capable of producing new ionizable lipids with available synthesis pathways.

cs.LG↗

arXiv2024

A Deep Generative Model for the Design of Synthesizable Ionizable Lipids

Lipid nanoparticles (LNPs) are vital in modern biomedicine, enabling the effective delivery of mRNA for vaccines and therapies by protecting it from rapid degradation. Among the components of LNPs, ionizable lipids play a key role in RNA protection and facilitate its delivery into the cytoplasm. However, designing ionizable lipids is complex. Deep generative models can accelerate this process and explore a larger candidate space compared to traditional methods. Due to the structural differences between lipids and small molecules, existing generative models used for small molecule generation are unsuitable for lipid generation. To address this, we developed a deep generative model specifically tailored for the discovery of ionizable lipids. Our model generates novel ionizable lipid structures and provides synthesis paths using synthetically accessible building blocks, addressing synthesizability. This advancement holds promise for streamlining the development of lipid-based delivery systems, potentially accelerating the deployment of new therapeutic agents, including mRNA vaccines and gene therapies.

cs.LG↗

arXiv2024

Accelerating Relative Entropy Coding with Space Partitioning

Relative entropy coding (REC) algorithms encode a random sample following a target distribution $Q$, using a coding distribution $P$ shared between the sender and receiver. Sadly, general REC algorithms suffer from prohibitive encoding times, at least on the order of $2^{D_{\text{KL}}[Q||P]}$, and faster algorithms are limited to very specific settings. This work addresses this issue by introducing a REC scheme utilizing space partitioning to reduce runtime in practical scenarios. We provide theoretical analyses of our method and demonstrate its effectiveness with both toy examples and practical applications. Notably, our method successfully handles REC tasks with $D_{\text{KL}}[Q||P]$ about three times greater than what previous methods can manage, and reduces the bitrate by approximately 5-15% in VAE-based lossless compression on MNIST and INR-based lossy compression on CIFAR-10, compared to previous methods, significantly improving the practicality of REC for neural compression.

cs.IT↗

arXiv2024

On conditional diffusion models for PDE simulations

Modelling partial differential equations (PDEs) is of crucial importance in science and engineering, and it includes tasks ranging from forecasting to inverse problems, such as data assimilation. However, most previous numerical and machine learning approaches that target forecasting cannot be applied out-of-the-box for data assimilation. Recently, diffusion models have emerged as a powerful tool for conditional generation, being able to flexibly incorporate observations without retraining. In this work, we perform a comparative study of score-based diffusion models for forecasting and assimilation of sparse observations. In particular, we focus on diffusion models that are either trained in a conditional manner, or conditioned after unconditional training. We address the shortcomings of existing models by proposing 1) an autoregressive sampling approach that significantly improves performance in forecasting, 2) a new training strategy for conditional score-based models that achieves stable performance over a range of history lengths, and 3) a hybrid model which employs flexible pre-training conditioning on initial conditions and flexible post-training conditioning to handle data assimilation. We empirically show that these modifications are crucial for successfully tackling the combination of forecasting and data assimilation, a task commonly encountered in real-world scenarios.

cs.LG↗

arXiv2024

Getting Free Bits Back from Rotational Symmetries in LLMs

Current methods for compressing neural network weights, such as decomposition, pruning, quantization, and channel simulation, often overlook the inherent symmetries within these networks and thus waste bits on encoding redundant information. In this paper, we propose a format based on bits-back coding for storing rotationally symmetric Transformer weights more efficiently than the usual array layout at the same floating-point precision. We evaluate our method on Large Language Models (LLMs) pruned by SliceGPT (Ashkboos et al., 2024) and achieve a 3-5% reduction in total bit usage for free across different model sizes and architectures without impacting model performance within a certain numerical precision.

cs.IT↗

arXiv2024

Efficient and Unbiased Sampling of Boltzmann Distributions via Consistency Models

Diffusion models have shown promising potential for advancing Boltzmann Generators. However, two critical challenges persist: (1) inherent errors in samples due to model imperfections, and (2) the requirement of hundreds of functional evaluations (NFEs) to achieve high-quality samples. While existing solutions like importance sampling and distillation address these issues separately, they are often incompatible, as most distillation models lack the necessary density information for importance sampling. This paper introduces a novel sampling method that effectively combines Consistency Models (CMs) with importance sampling. We evaluate our approach on both synthetic energy functions and equivariant n-body particle systems. Our method produces unbiased samples using only 6-25 NFEs while achieving a comparable Effective Sample Size (ESS) to Denoising Diffusion Probabilistic Models (DDPMs) that require approximately 100 NFEs.

cs.LG↗

arXiv2024

Improving Antibody Design with Force-Guided Sampling in Diffusion Models

Antibodies, crucial for immune defense, primarily rely on complementarity-determining regions (CDRs) to bind and neutralize antigens, such as viruses. The design of these CDRs determines the antibody's affinity and specificity towards its target. Generative models, particularly denoising diffusion probabilistic models (DDPMs), have shown potential to advance the structure-based design of CDR regions. However, only a limited dataset of bound antibody-antigen structures is available, and generalization to out-of-distribution interfaces remains a challenge. Physics based force-fields, which approximate atomic interactions, offer a coarse but universal source of information to better mold designs to target interfaces. Integrating this foundational information into diffusion models is, therefore, highly desirable. Here, we propose a novel approach to enhance the sampling process of diffusion models by integrating force field energy-based feedback. Our model, DiffForce, employs forces to guide the diffusion sampling process, effectively blending the two distributions. Through extensive experiments, we demonstrate that our method guides the model to sample CDRs with lower energy, enhancing both the structure and sequence of the generated antibodies.

q-bio.QM↗

arXiv2024

Leveraging Task Structures for Improved Identifiability in Neural Network Representations

This work extends the theory of identifiability in supervised learning by considering the consequences of having access to a distribution of tasks. In such cases, we show that linear identifiability is achievable in the general multi-task regression setting. Furthermore, we show that the existence of a task distribution which defines a conditional prior over latent factors reduces the equivalence class for identifiability to permutations and scaling of the true latent factors, a stronger and more useful result than linear identifiability. Crucially, when we further assume a causal structure over these tasks, our approach enables simple maximum marginal likelihood optimization, and suggests potential downstream applications to causal representation learning. Empirically, we find that this straightforward optimization procedure enables our model to outperform more general unsupervised models in recovering canonical representations for both synthetic data and real-world molecular data.

stat.ML↗

arXiv2024

Position: Bayesian Deep Learning is Needed in the Age of Large-Scale AI

In the current landscape of deep learning research, there is a predominant emphasis on achieving high predictive accuracy in supervised tasks involving large image and language datasets. However, a broader perspective reveals a multitude of overlooked metrics, tasks, and data types, such as uncertainty, active and continual learning, and scientific data, that demand attention. Bayesian deep learning (BDL) constitutes a promising avenue, offering advantages across these diverse settings. This paper posits that BDL can elevate the capabilities of deep learning. It revisits the strengths of BDL, acknowledges existing challenges, and highlights some exciting research avenues aimed at addressing these obstacles. Looking ahead, the discussion focuses on possible ways to combine large-scale foundation models with BDL to unlock their full potential.

cs.LG↗

arXiv2024

Diagnosing and fixing common problems in Bayesian optimization for molecule design

Bayesian optimization (BO) is a principled approach to molecular design tasks. In this paper we explain three pitfalls of BO which can cause poor empirical performance: an incorrect prior width, over-smoothing, and inadequate acquisition function maximization. We show that with these issues addressed, even a basic BO setup is able to achieve the highest overall performance on the PMO benchmark for molecule design (Gao et al 2022). These results suggest that BO may benefit from more attention in the machine learning for molecules community.

cs.LG↗

arXiv2024

Studying K-FAC Heuristics by Viewing Adam through a Second-Order Lens

Research into optimisation for deep learning is characterised by a tension between the computational efficiency of first-order, gradient-based methods (such as SGD and Adam) and the theoretical efficiency of second-order, curvature-based methods (such as quasi-Newton methods and K-FAC). Noting that second-order methods often only function effectively with the addition of stabilising heuristics (such as Levenberg-Marquardt damping), we ask how much these (as opposed to the second-order curvature model) contribute to second-order algorithms' performance. We thus study AdamQLR: an optimiser combining damping and learning rate selection techniques from K-FAC (Martens & Grosse, 2015) with the update directions proposed by Adam, inspired by considering Adam through a second-order lens. We evaluate AdamQLR on a range of regression and classification tasks at various scales and hyperparameter tuning methodologies, concluding K-FAC's adaptive heuristics are of variable standalone general effectiveness, and finding an untuned AdamQLR setting can achieve comparable performance vs runtime to tuned benchmarks.

cs.LG↗

arXiv2024

Diffusive Gibbs Sampling

The inadequate mixing of conventional Markov Chain Monte Carlo (MCMC) methods for multi-modal distributions presents a significant challenge in practical applications such as Bayesian inference and molecular dynamics. Addressing this, we propose Diffusive Gibbs Sampling (DiGS), an innovative family of sampling methods designed for effective sampling from distributions characterized by distant and disconnected modes. DiGS integrates recent developments in diffusion models, leveraging Gaussian convolution to create an auxiliary noisy distribution that bridges isolated modes in the original space and applying Gibbs sampling to alternately draw samples from both spaces. A novel Metropolis-within-Gibbs scheme is proposed to enhance mixing in the denoising sampling step. DiGS exhibits a better mixing property for sampling multi-modal distributions than state-of-the-art methods such as parallel tempering, attaining substantially improved performance across various tasks, including mixtures of Gaussians, Bayesian neural networks and molecular dynamics.

stat.ML↗

arXiv2024

Warm Start Marginal Likelihood Optimisation for Iterative Gaussian Processes

Gaussian processes are a versatile probabilistic machine learning model whose effectiveness often depends on good hyperparameters, which are typically learned by maximising the marginal likelihood. In this work, we consider iterative methods, which use iterative linear system solvers to approximate marginal likelihood gradients up to a specified numerical precision, allowing a trade-off between compute time and accuracy of a solution. We introduce a three-level hierarchy of marginal likelihood optimisation for iterative Gaussian processes, and identify that the computational costs are dominated by solving sequential batches of large positive-definite systems of linear equations. We then propose to amortise computations by reusing solutions of linear system solvers as initialisations in the next step, providing a $\textit{warm start}$. Finally, we discuss the necessary conditions and quantify the consequences of warm starts and demonstrate their effectiveness on regression tasks, where warm starts achieve the same results as the conventional procedure while providing up to a $16 \times$ average speed-up among datasets.

cs.LG↗