arXiv subjects

Jose Miguel Hernandez-Lobato

Publications and source records attributed to Jose Miguel Hernandez-Lobato.

14 recordsLinked to original sources

arXiv2026

A Machine Learning Benchmarking Framework for Lipid Nanoparticle Transfection Efficiency Prediction

The discovery of new ionizable lipids for efficient lipid nanoparticle (LNP)-mediated RNA delivery remains a major bottleneck in RNA therapeutics development. Recent advances demonstrate the potential of machine learning (ML) models to predict transfection efficiency directly from lipid structure, enabling high-throughput virtual screening and accelerating lead identification. However, as new models for LNP transfection prediction continue to emerge, the lack of rigorous and standardized benchmarking poses a significant risk and may undermine confidence in their reliability for discovery. Here, we present a robust ML benchmarking framework for evaluating transfection prediction models based on ionizable lipid structures. This framework systematically benchmarks diverse molecular representations paired with a broad range of ML architectures spanning traditional models, feedforward neural networks, and state-of-the-art graph-based methods. In addition, the presented framework supports assessment of model generalization and evaluates prediction reliability beyond standard regression metrics. Using a curated dataset of 1,100 unique ionizable lipid structures derived from the HeLa transfection dataset originally reported by Xu et al., we show that within this framework, models leveraging explicit molecular substructure encoding consistently achieve the highest predictive accuracy and should serve as essential baselines for the development of new, more sophisticated models. In contrast, some current graph-based models, including AGILE, Chemprop, and KPGT, tend to show comparatively lower accuracy. The presented framework provides a standardized, transparent, and comprehensive benchmarking resource that enables meaningful comparison of emerging architectures and establishes strong baselines for future development of predictive models in lipid-based RNA delivery.

q-bio.QM↗

arXiv2026

Few-Step Boltzmann Generators via Scalable Likelihood Flow Maps

Recent progress in flow-based generative modeling has led to models that output high-quality samples while using only a small number of function evaluations. However, at present, there is a lack of similar advances in estimating the model likelihood. In particular, most existing methods either rely on restrictive architectures that enable exact calculations, or use stochastic approximations such as Hutchinson's trace estimator that introduce substantial variance. In this work, we introduce SCAlable LikeLihood distillation of flOw maPs (SCALLOP). SCALLOP builds on the recently proposed F2D2, a likelihood flow map model that can generate samples and their densities in a small number of function evaluations. While F2D2 uses Hutchinson's estimator during training, we introduce an alternative and more scalable likelihood distillation objective that is Hutchinson-free and admits a vectorized formulation. Empirically, we demonstrate the effectiveness of SCALLOP as a Boltzmann generator in molecular science, and further validate its benefit on image datasets. SCALLOP significantly reduces both training variance and training time while consistently improving performance compared to F2D2, and is competitive with the state-of-the-art while achieving up to 10x inference speedup over the fastest baseline.

cs.LG↗

arXiv2026

Training-Free Vector Quantization via Gaussian VAEs

Vector-quantized variational autoencoders (VQ-VAEs) are discrete autoencoders that compress images into discrete tokens. However, they are difficult to train due to discretization. In this paper, we propose a simple yet effective technique dubbed Gaussian Quant (GQ), which first trains a Gaussian VAE under certain constraints and then converts it into a VQ-VAE without additional training. For conversion, GQ generates random Gaussian noise as a codebook and finds the closest noise vector to the posterior mean. Theoretically, we prove that when the logarithm of the codebook size exceeds the bits-back coding rate of the Gaussian VAE, a small quantization error is guaranteed. Practically, we propose a heuristic to train Gaussian VAEs for effective conversion, named the target divergence constraint (TDC). Empirically, we show that GQ outperforms previous VQ-VAEs, such as VQGAN, FSQ, LFQ, and BSQ, on both UNet and ViT architectures. Furthermore, TDC also improves previous Gaussian VAE discretization methods, such as TokenBridge. The source code is provided in https://github.com/tongdaxu/VQ-VAE-from-Gaussian-VAE.

cs.LG↗

arXiv2026

Making Reconstruction FID Predictive of Diffusion Generation FID

It is well known that the reconstruction FID (rFID) of a VAE is poorly correlated with the generation FID (gFID) of a latent diffusion model. We propose interpolated FID (iFID), a simple variant of rFID that exhibits a strong correlation with gFID. Specifically, for each dataset element, we retrieve its nearest neighbor in latent space, interpolate between their latent representations, decode the interpolated latent, and compute the FID between the decoded samples and the original dataset. We provide an intuitive explanation for why iFID correlates well with gFID, and why reconstruction metrics can be negatively correlated with gFID, by connecting iFID to recent results on diffusion generalization and hallucination. Theoretically, we show that iFID evaluates decoded interpolations aligned with the ridge set around which diffusion samples concentrate, thereby measuring a quantity closely related to diffusion sample quality. Empirically, iFID is the first metric shown to strongly correlate with diffusion gFID across diverse VAEs, achieving Pearson and Spearman correlations of approximately $0.85$. The project page is available at https://tongdaxu.github.io/pages/ifid.html.

cs.CV↗

arXiv2026

A Gaussian Process View on Observation Noise and Initialization in Wide Neural Networks

Performing gradient descent in a wide neural network is equivalent to computing the posterior mean of a Gaussian Process with the Neural Tangent Kernel (NTK-GP), for a specific prior mean and with zero observation noise. However, existing formulations have two limitations: (i) the NTK-GP assumes noiseless targets, leading to misspecification on noisy data; (ii) the equivalence does not extend to arbitrary prior means, which are essential for well-specified models. To address (i), we introduce a regularizer into the training objective, showing its correspondence to incorporating observation noise in the NTK-GP. To address (ii), we propose a \textit{shifted network} that enables arbitrary prior means and allows obtaining the posterior mean with gradient descent on a single network, without ensembling or kernel inversion. We validate our results with experiments across datasets and architectures, showing that this approach removes key obstacles to the practical use of NTK-GP equivalence in applied Gaussian process modeling.

cs.LG↗

arXiv2026

Weighted Conditional Flow Matching

Conditional flow matching (CFM) has emerged as a powerful framework for training continuous normalizing flows due to its computational efficiency and effectiveness. However, standard CFM often produces paths that deviate significantly from straight-line interpolations between prior and target distributions, making generation slower and less accurate due to the need for fine discretization at inference. Recent methods enhance CFM performance by inducing shorter and straighter trajectories but typically rely on computationally expensive mini-batch optimal transport (OT). Drawing insights from entropic optimal transport (EOT), we propose Weighted Conditional Flow Matching (W-CFM), a novel approach that modifies the classical CFM loss by weighting each training pair $(x, y)$ with a Gibbs kernel. We show that this weighting recovers the entropic OT coupling up to some bias in the marginals, and we provide the conditions under which the marginals remain nearly unchanged. Moreover, we establish an equivalence between W-CFM and the minibatch OT method in the large-batch limit, showing how our method overcomes computational and performance bottlenecks linked to batch size. Empirically, we test our method on unconditional generation on various synthetic and real datasets, confirming that W-CFM achieves comparable or superior sample quality, fidelity, and diversity to other alternative baselines while maintaining the computational efficiency of vanilla CFM.

cs.LG↗

arXiv2025

Mitigating Forgetting in Low Rank Adaptation

Parameter-efficient fine-tuning methods, such as Low-Rank Adaptation (LoRA), enable fast specialization of large pre-trained models to different downstream applications. However, this process often leads to catastrophic forgetting of the model's prior domain knowledge. We address this issue with LaLoRA, a weight-space regularization technique that applies a Laplace approximation to Low-Rank Adaptation. Our approach estimates the model's confidence in each parameter and constrains updates in high-curvature directions, preserving prior knowledge while enabling efficient target-domain learning. By applying the Laplace approximation only to the LoRA weights, the method remains lightweight. We evaluate LaLoRA by fine-tuning a Llama model for mathematical reasoning and demonstrate an improved learning-forgetting trade-off, which can be directly controlled via the method's regularization strength. We further explore different loss landscape curvature approximations for estimating parameter confidence, analyze the effect of the data used for the Laplace approximation, and study robustness across hyperparameters.

cs.LG↗

arXiv2025

Uncertainty Modeling in Graph Neural Networks via Stochastic Differential Equations

We propose a novel Stochastic Differential Equation (SDE) framework to address the problem of learning uncertainty-aware representations for graph-structured data. While Graph Neural Ordinary Differential Equations (GNODEs) have shown promise in learning node representations, they lack the ability to quantify uncertainty. To address this, we introduce Latent Graph Neural Stochastic Differential Equations (LGNSDE), which enhance GNODE by embedding randomness through a Bayesian prior-posterior mechanism for epistemic uncertainty and Brownian motion for aleatoric uncertainty. By leveraging the existence and uniqueness of solutions to graph-based SDEs, we prove that the variance of the latent space bounds the variance of model outputs, thereby providing theoretically sensible guarantees for the uncertainty estimates. Furthermore, we show mathematically that LGNSDEs are robust to small perturbations in the input, maintaining stability over time. Empirical results across several benchmarks demonstrate that our framework is competitive in out-of-distribution detection, robustness to noise, and active learning, underscoring the ability of LGNSDEs to quantify uncertainty reliably. Code is available at \href{https://github.com/Richard-Bergna/GraphNeuralSDE}{\texttt{github.com/Richard-Bergna/GraphNeuralSDE}}.

cs.LG↗

arXiv2025

Post-Hoc Uncertainty Quantification in Pre-Trained Neural Networks via Activation-Level Gaussian Processes

Uncertainty quantification in neural networks through methods such as Dropout, Bayesian neural networks and Laplace approximations is either prone to underfitting or computationally demanding, rendering these approaches impractical for large-scale datasets. In this work, we address these shortcomings by shifting the focus from uncertainty in the weight space to uncertainty at the activation level, via Gaussian processes. More specifically, we introduce the Gaussian Process Activation function (GAPA) to capture neuron-level uncertainties. Our approach operates in a post-hoc manner, preserving the original mean predictions of the pre-trained neural network and thereby avoiding the underfitting issues commonly encountered in previous methods. We propose two methods. The first, GAPA-Free, employs empirical kernel learning from the training data for the hyperparameters and is highly efficient during training. The second, GAPA-Variational, learns the hyperparameters via gradient descent on the kernels, thus affording greater flexibility. Empirical results demonstrate that GAPA-Variational outperforms the Laplace approximation on most datasets in at least one of the uncertainty quantification metrics.

stat.ML↗

arXiv2024

Feature Attribution with Necessity and Sufficiency via Dual-stage Perturbation Test for Causal Explanation

We investigate the problem of explainability for machine learning models, focusing on Feature Attribution Methods (FAMs) that evaluate feature importance through perturbation tests. Despite their utility, FAMs struggle to distinguish the contributions of different features, when their prediction changes are similar after perturbation. To enhance FAMs' discriminative power, we introduce Feature Attribution with Necessity and Sufficiency (FANS), which find a neighborhood of the input such that perturbing samples within this neighborhood have a high Probability of being Necessity and Sufficiency (PNS) cause for the change in predictions, and use this PNS as the importance of the feature. Specifically, FANS compute this PNS via a heuristic strategy for estimating the neighborhood and a perturbation test involving two stages (factual and interventional) for counterfactual reasoning. To generate counterfactual samples, we use a resampling-based approach on the observed samples to approximate the required conditional distribution. We demonstrate that FANS outperforms existing attribution methods on six benchmarks. Please refer to the source code via \url{https://github.com/DMIRLAB-Group/FANS}.

cs.LG↗

arXiv2023

Graph Neural Stochastic Differential Equations

We present a novel model Graph Neural Stochastic Differential Equations (Graph Neural SDEs). This technique enhances the Graph Neural Ordinary Differential Equations (Graph Neural ODEs) by embedding randomness into data representation using Brownian motion. This inclusion allows for the assessment of prediction uncertainty, a crucial aspect frequently missed in current models. In our framework, we spotlight the \textit{Latent Graph Neural SDE} variant, demonstrating its effectiveness. Through empirical studies, we find that Latent Graph Neural SDEs surpass conventional models like Graph Convolutional Networks and Graph Neural ODEs, especially in confidence prediction, making them superior in handling out-of-distribution detection across both static and spatio-temporal contexts.

cs.LG↗

arXiv2021

Results and Insights from Diagnostic Questions: The NeurIPS 2020 Education Challenge

This competition concerns educational diagnostic questions, which are pedagogically effective, multiple-choice questions (MCQs) whose distractors embody misconceptions. With a large and ever-increasing number of such questions, it becomes overwhelming for teachers to know which questions are the best ones to use for their students. We thus seek to answer the following question: how can we use data on hundreds of millions of answers to MCQs to drive automatic personalized learning in large-scale learning scenarios where manual personalization is infeasible? Success in using MCQ data at scale helps build more intelligent, personalized learning platforms that ultimately improve the quality of education en masse. To this end, we introduce a new, large-scale, real-world dataset and formulate 4 data mining tasks on MCQs that mimic real learning scenarios and target various aspects of the above question in a competition setting at NeurIPS 2020. We report on our NeurIPS competition in which nearly 400 teams submitted approximately 4000 submissions, with encouragingly diverse and effective approaches to each of our tasks.

cs.CY↗

arXiv2021

Educational Question Mining At Scale: Prediction, Analysis and Personalization

Online education platforms enable teachers to share a large number of educational resources such as questions to form exercises and quizzes for students. With large volumes of available questions, it is important to have an automated way to quantify their properties and intelligently select them for students, enabling effective and personalized learning experiences. In this work, we propose a framework for mining insights from educational questions at scale. We utilize the state-of-the-art Bayesian deep learning method, in particular partial variational auto-encoders (p-VAE), to analyze real students' answers to a large collection of questions. Based on p-VAE, we propose two novel metrics that quantify question quality and difficulty, respectively, and a personalized strategy to adaptively select questions for students. We apply our proposed framework to a real-world dataset with tens of thousands of questions and tens of millions of answers from an online education platform. Our framework not only demonstrates promising results in terms of statistical metrics but also obtains highly consistent results with domain experts' evaluation.

cs.CY↗

arXiv2015

Stochastic Expectation Propagation

Expectation propagation (EP) is a deterministic approximation algorithm that is often used to perform approximate Bayesian parameter learning. EP approximates the full intractable posterior distribution through a set of local approximations that are iteratively refined for each datapoint. EP can offer analytic and computational advantages over other approximations, such as Variational Inference (VI), and is the method of choice for a number of models. The local nature of EP appears to make it an ideal candidate for performing Bayesian learning on large models in large-scale dataset settings. However, EP has a crucial limitation in this context: the number of approximating factors needs to increase with the number of data-points, N, which often entails a prohibitively large memory overhead. This paper presents an extension to EP, called stochastic expectation propagation (SEP), that maintains a global posterior approximation (like VI) but updates it in a local way (like EP). Experiments on a number of canonical learning problems using synthetic and real-world datasets indicate that SEP performs almost as well as full EP, but reduces the memory consumption by a factor of $N$. SEP is therefore ideally suited to performing approximate Bayesian learning in the large model, large dataset setting.

stat.ML↗