PerturbDiff: Functional Diffusion for Single-Cell Perturbation Modeling

Building Virtual Cells that can accurately simulate cellular responses to perturbations is a long-standing goal in systems biology. A fundamental challenge is that high-throughput single-cell sequencing is destructive: the same cell cannot be observed both before and after a perturbation. Thus, perturbation prediction requires mapping unpaired control and perturbed populations. Existing models address this by learning maps between distributions, but typically assume a single fixed response distribution when conditioned on observed cellular context (e.g., cell type) and the perturbation type. In reality, responses vary systematically due to unobservable latent factors such as microenvironmental fluctuations and complex batch effects, forming a manifold of possible distributions for the same observed conditions. To account for this variability, we introduce PerturbDiff, which shifts modeling from individual cells to entire distributions. By embedding distributions as points in a Hilbert space, we define a diffusion-based generative process operating directly over probability distributions. This allows PerturbDiff to capture population-level response shifts across hidden factors. Benchmarks on established datasets show that PerturbDiff achieves state-of-the-art performance in single-cell response prediction and generalizes substantially better to unseen perturbations. See our project page (https://katarinayuan.github.io/PerturbDiff-ProjectPage/), where code and data will be made publicly available (https://github.com/DeepGraphLearning/PerturbDiff).

Mind the GAP: Improving Robustness to Subpopulation Shifts with Group-Aware Priors

Machine learning models often perform poorly under subpopulation shifts in the data distribution. Developing methods that allow machine learning models to better generalize to such shifts is crucial for safe deployment in real-world settings. In this paper, we develop a family of group-aware prior (GAP) distributions over neural network parameters that explicitly favor models that generalize well under subpopulation shifts. We design a simple group-aware prior that only requires access to a small set of data with group information and demonstrate that training with this prior yields state-of-the-art performance -- even when only retraining the final layer of a previously trained non-robust model. Group aware-priors are conceptually simple, complementary to existing approaches, such as attribute pseudo labeling and data reweighting, and open up promising new avenues for harnessing Bayesian inference to enable robustness to subpopulation shifts.

Manipulating Sparse Double Descent

This paper investigates the double descent phenomenon in two-layer neural networks, focusing on the role of L1 regularization and representation dimensions. It explores an alternative double descent phenomenon, named sparse double descent. The study emphasizes the complex relationship between model complexity, sparsity, and generalization, and suggests further research into more diverse models and datasets. The findings contribute to a deeper understanding of neural network training and optimization.

On the Robustness of Neural Collapse and the Neural Collapse of Robustness

Neural Collapse refers to the curious phenomenon in the end of training of a neural network, where feature vectors and classification weights converge to a very simple geometrical arrangement (a simplex). While it has been observed empirically in various cases and has been theoretically motivated, its connection with crucial properties of neural networks, like their generalization and robustness, remains unclear. In this work, we study the stability properties of these simplices. We find that the simplex structure disappears under small adversarial attacks, and that perturbed examples "leap" between simplex vertices. We further analyze the geometry of networks that are optimized to be robust against adversarial perturbations of the input, and find that Neural Collapse is a pervasive phenomenon in these cases as well, with clean and perturbed representations forming aligned simplices, and giving rise to a robust simple nearest-neighbor classifier. By studying the propagation of the amount of collapse inside the network, we identify novel properties of both robust and non-robust machine learning models, and show that earlier, unlike later layers maintain reliable simplices on perturbed data.