Mats Jirstrand

Anders Sjöberg, Jakob Lindqvist, Magnus Önnheim et al.

Diffusion models can be parameterized in terms of either a score or an energy function. The energy parameterization is attractive as it enables sampling procedures such as Markov Chain Monte Carlo (MCMC) that incorporates a Metropolis-Hastings (MH) correction step based on energy differences between proposed samples. Such corrections can significantly improve sampling quality, particularly in the context of model composition, where pre-trained models are combined to generate samples from novel distributions. Score-based diffusion models, on the other hand, are more widely adopted and come with a rich ecosystem of pre-trained models. However, they do not, in general, define an underlying energy function, making MH-based sampling inapplicable. In this work, we address this limitation by retaining the score parameterization and introducing a novel MH-like acceptance rule based on line integration of the score function. This allows the reuse of existing diffusion models while still combining the reverse process with various MCMC techniques, viewed as an instance of annealed MCMC. Through experiments on synthetic and real-world data, we show that our MH-like samplers offer comparable improvements to those obtained with energy-based models, without requiring explicit energy parameterization.

Anders Sjöberg, Nils Olsson, Marcus Baaz et al.

Longitudinal tumor measurements, dropout information, and genetic covariates provide complementary information about treatment response, but integrating these data sources within a single population modeling framework remains challenging. We extend the empirical Bayes variational autoencoder (EB-VAE) framework to joint longitudinal and time-to-event modeling and evaluate it on tumor growth data. The framework represents inter-individual variability using latent individual effects regularized by a covariate-conditioned empirical Bayes prior, while a decoder maps these latent effects to tumor-volume trajectories. To account for informative dropout, the decoder was augmented with a hazard model, yielding joint predictions of tumor growth and time to dropout. We further compared fully neural and hybrid semi-mechanistic decoder formulations and incorporated genomic covariates through a genetics-conditioned prior adaptation. The hybrid decoder recovered treatment-effect parameters broadly consistent with previously reported nonlinear mixed-effects estimates, while achieving prior predictive performance comparable to the neural decoder. The joint model reproduced both tumor-volume distributions and dropout patterns in held-out individuals, and genetic conditioning improved individual-level prior predictions in both cutaneous melanoma and breast cancer experiments. Stability selection identified several biologically plausible genetic indicators, including alterations in BRAF, NRAS, NF1, and MDM2. These results demonstrate that EB-VAE provides a flexible probabilistic framework for combining neural dynamics, mechanistic structure, time-to-event modeling, and high-dimensional covariates in pharmacometric applications.

Gregor Ulm, Simon Smith, Adrian Nilsson et al.

Clustering is an essential data mining tool for analyzing and grouping similar objects. In big data applications, however, many clustering algorithms are infeasible due to their high memory requirements and/or unfavorable runtime complexity. In contrast, Contraction Clustering (RASTER) is a single-pass algorithm for identifying density-based clusters with linear time complexity. Due to its favorable runtime and the fact that its memory requirements are constant, this algorithm is highly suitable for big data applications where the amount of data to be processed is huge. It consists of two steps: (1) a contraction step which projects objects onto tiles and (2) an agglomeration step which groups tiles into clusters. This algorithm is extremely fast in both sequential and parallel execution. Our quantitative evaluation shows that a sequential implementation of RASTER performs significantly better than various standard clustering algorithms. Furthermore, the parallel speedup is significant: on a contemporary workstation, an implementation in Rust processes a batch of 500 million points with 1 million clusters in less than 50 seconds on one core. With 8 cores, the algorithm is about four times faster.