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PerturbDiff: Functional Diffusion for Single-Cell Perturbation Modeling

arXiv:2602.19685v1 Announce Type: cross Abstract: 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).

Simulating the Real World: A Unified Survey of Multimodal Generative Models

17 February 2026 at 13:00
arXiv:2503.04641v3 Announce Type: replace-cross Abstract: Understanding and replicating the real world is a critical challenge in Artificial General Intelligence (AGI) research. To achieve this, many existing approaches, such as world models, aim to capture the fundamental principles governing the physical world, enabling more accurate simulations and meaningful interactions. However, current methods often treat different modalities, including 2D (images), videos, 3D, and 4D representations, as independent domains, overlooking their interdependencies. Additionally, these methods typically focus on isolated dimensions of reality without systematically integrating their connections. In this survey, we present a unified survey for multimodal generative models that investigate the progression of data dimensionality in real-world simulation. Specifically, this survey starts from 2D generation (appearance), then moves to video (appearance+dynamics) and 3D generation (appearance+geometry), and finally culminates in 4D generation that integrate all dimensions. To the best of our knowledge, this is the first attempt to systematically unify the study of 2D, video, 3D and 4D generation within a single framework. To guide future research, we provide a comprehensive review of datasets, evaluation metrics and future directions, and fostering insights for newcomers. This survey serves as a bridge to advance the study of multimodal generative models and real-world simulation within a unified framework.
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