scMultiSim: simulation of single cell multi-omics and spatial data guided by gene regulatory networks and cell-cell interactions.

Simulated single-cell data is essential for designing and evaluating computational methods in the absence of experimental ground truth. Existing simulators typically focus on modeling one or two specific biological factors or mechanisms that affect the output data, which limits their capacity to simulate the complexity and multi-modality in real data. Here, we present scMultiSim, an in silico simulator that generates multi-modal single-cell data, including gene expression, chromatin accessibility, RNA velocity, and spatial cell locations while accounting for the relationships between modalities. scMultiSim jointly models various biological factors that affect the output data, including cell identity, within-cell gene regulatory networks (GRNs), cell-cell interactions (CCIs), and chromatin accessibility, hile also incorporating technical noises. Moreover, it allows users to adjust each factor's effect easily. We validated scMultiSim's simulated biological effects and demonstrated its applications by benchmarking a wide range of computational tasks, including multi-modal and multi-batch data integration, RNA velocity estimation, GRN inference and CCI inference using spatially resolved gene expression data, many of them were not benchmarked before due to the lack of proper tools. Compared to existing simulators, scMultiSim can benchmark a much broader range of existing computational problems and even new potential tasks.