CFM-GP: Unified Conditional Flow Matching to Learn Gene Perturbation Across Cell Types
This provides a scalable solution for functional genomics, addressing the costly and time-consuming data collection in single-cell technologies, though it is incremental as it builds on existing flow matching methods.
The paper tackled the problem of predicting gene perturbation effects across diverse cell types by developing CFM-GP, a unified model that outperformed state-of-the-art baselines in R-squared and Spearman correlation across five datasets, including SARS-CoV-2 infection and IFN-beta stimulation.
Understanding gene perturbation effects across diverse cellular contexts is a central challenge in functional genomics, with important implications for therapeutic discovery and precision medicine. Single-cell technologies enable high-resolution measurement of transcriptional responses, but collecting such data is costly and time-consuming, especially when repeated for each cell type. Existing computational methods often require separate models per cell type, limiting scalability and generalization. We present CFM-GP, a method for cell type-agnostic gene perturbation prediction. CFM-GP learns a continuous, time-dependent transformation between unperturbed and perturbed gene expression distributions, conditioned on cell type, allowing a single model to predict across all cell types. Unlike prior approaches that use discrete modeling, CFM-GP employs a flow matching objective to capture perturbation dynamics in a scalable manner. We evaluate on five datasets: SARS-CoV-2 infection, IFN-beta stimulated PBMCs, glioblastoma treated with Panobinostat, lupus under IFN-beta stimulation, and Statefate progenitor fate mapping. CFM-GP consistently outperforms state-of-the-art baselines in R-squared and Spearman correlation, and pathway enrichment analysis confirms recovery of key biological pathways. These results demonstrate the robustness and biological fidelity of CFM-GP as a scalable solution for cross-cell type gene perturbation prediction.