PerturBench: Benchmarking Machine Learning Models for Cellular Perturbation Analysis
Yan Wu, Esther Wershof, Sebastian Schmon, Marcel Nassar, Błażej Osiński, Ridvan Eksi, Zichao Yan, Rory Stark, Kun Zhang, Thore Graepel
We introduce a comprehensive framework for perturbation response modeling in single cells, 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 nuances. 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 advances the potential of these models to use high-throughput genetic and chemical screens for disease target discovery.