In-silico biological discovery with large perturbation models

Data generated in perturbation experiments link perturbations to the changes they elicit and therefore contain information relevant to numerous biological discovery tasks -- from understanding the relationships between biological entities to developing therapeutics. However, these data encompass diverse perturbations and readouts, and the complex dependence of experimental outcomes on their biological context makes it challenging to integrate insights across experiments. Here, we present the Large Perturbation Model (LPM), a deep-learning model that integrates multiple, heterogeneous perturbation experiments by representing perturbation, readout, and context as disentangled dimensions. LPM outperforms existing methods across multiple biological discovery tasks, including in predicting post-perturbation transcriptomes of unseen experiments, identifying shared molecular mechanisms of action between chemical and genetic perturbations, and facilitating the inference of gene-gene interaction networks.

Diffusion Models for Video Prediction and Infilling

To predict and anticipate future outcomes or reason about missing information in a sequence is a key ability for agents to be able to make intelligent decisions. This requires strong temporally coherent generative capabilities. Diffusion models have shown huge success in several generative tasks lately, but have not been extensively explored in the video domain. We present Random-Mask Video Diffusion (RaMViD), which extends image diffusion models to videos using 3D convolutions, and introduces a new conditioning technique during training. By varying the mask we condition on, the model is able to perform video prediction, infilling and upsampling. Since we do not use concatenation to condition on a mask, as done in most conditionally trained diffusion models, we are able to decrease the memory footprint. We evaluated the model on two benchmark datasets for video prediction and one for video generation on which we achieved competitive results. On Kinetics-600 we achieved state-of-the-art for video prediction.