We introduce a comprehensive framework for modeling single cell transcriptomic responses to perturbations, aimed at standardizing benchmarking in this rapidly evolving field. Our approach includes a modular and user-friendly model development and evaluation platform, a collection of diverse perturbational datasets, and a set of metrics designed to fairly compare models and dissect their performance. Through extensive evaluation of both published and baseline models across diverse datasets, we highlight the limitations of widely used models, such as mode collapse. We also demonstrate the importance of rank metrics which complement traditional model fit measures, such as RMSE, for validating model effectiveness. Notably, our results show that while no single model architecture clearly outperforms others, simpler architectures are generally competitive and scale well with larger datasets. Overall, this benchmarking exercise sets new standards for model evaluation, supports robust model development, and furthers the use of these models to simulate genetic and chemical screens for therapeutic discovery.

Sampling physical systems with rough energy landscapes is hindered by rare events and metastable trapping. While Boltzmann generators already offer a solution, their reliance on the reverse Kullback--Leibler divergence frequently induces catastrophic mode collapse, missing specific modes in multi-modal distributions. Here, we introduce the Jeffreys Flow, a robust generative framework that mitigates this failure by distilling empirical sampling data from Parallel Tempering trajectories using the symmetric Jeffreys divergence. This formulation effectively balances local target-seeking precision with global modes coverage. We show that minimizing Jeffreys divergence suppresses mode collapse and structurally corrects inherent inaccuracies via distillation of the empirical reference data. We demonstrate the framework's scalability and accuracy on highly non-convex multidimensional benchmarks, including the systematic correction of stochastic gradient biases in Replica Exchange Stochastic Gradient Langevin Dynamics and the massive acceleration of exact importance sampling in Path Integral Monte Carlo for quantum thermal states.

Generative adversarial networks (GANs) are a technique for learning generative models of complex data distributions from samples. Despite remarkable advances in generating realistic images, a major shortcoming of GANs is the fact that they tend to produce samples with little diversity, even when trained on diverse datasets. This phenomenon, known as mode collapse, has been the focus of much recent work. We study a principled approach to handling mode collapse, which we call packing. The main idea is to modify the discriminator to make decisions based on multiple samples from the same class, either real or artificially generated. We draw analysis tools from binary hypothesis testing---in particular the seminal result of Blackwell---to prove a fundamental connection between packing and mode collapse. We show that packing naturally penalizes generators with mode collapse, thereby favoring generator distributions with less mode collapse during the training process. Numerical experiments on benchmark datasets suggest that packing provides significant improvements.

Neural Information Processing Systems http://nips.cc/

Their performance is well measured by the cross-entropy (CE) of the model distribution relative to the data distribution.

Neural Information Processing Systems http://nips.cc/

Exten-sive experiments show the effectiveness of this measure to rank different GANmodels and capture the typical GAN failure scenarios, including mode collapse andnon-convergentbehaviours.

Neural Information Processing Systems http://nips.cc/