RT Journal Article SR Electronic T1 MultiCPA: Multimodal Compositional Perturbation Autoencoder JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.07.08.499049 DO 10.1101/2022.07.08.499049 A1 Inecik, Kemal A1 Uhlmann, Andreas A1 Lotfollahi, Mohammad A1 Theis, Fabian YR 2022 UL http://biorxiv.org/content/early/2022/07/10/2022.07.08.499049.abstract AB Single-cell multimodal profiling provides a high-resolution view of cellular information. Recently, multimodal profiling approaches have been coupled with CRISPR technologies to perform pooled screens of single or combinatorial perturbations. This opens the possibility of exploring the massive space of combinatorial perturbations and their regulatory effects computationally from the extrapolation of a few experimentally feasible combinations. Here, we propose MultiCPA, an end-to-end generative architecture to predict multimodal perturbation response at single cell level. Two mixing strategies to integrate multiple modalities are introduced and compared with existing methods. MultiCPA was also shown to accurately predict unseen combinatorial perturbation responses for multiple modalities. The code to reproduce the results is available on GitHub, theislab/multicpa.Competing Interest StatementF.J.T. consults for Immunai Inc., Singularity Bio B.V., CytoReason Ltd, and Omniscope Ltd, and has ownership interest in Dermagnostix GmbH and Cellarity.