RADF: Reference-Anchored Dynamic Flow for Observed-Perturbation Spatial Completion

Spatial perturbation profiling reveals how genetic interventions alter transcription across tissue locations, but destructive assays leave many perturbation-by-location response populations unmeasured. We study observed-perturbation spatial completion: given a reported response population for one intervention and a query coordinate scaffold, estimate the held-out response population. Predictions are unpaired and evaluated as populations; we do not claim prediction for unseen interventions or cell-to-location matching. RADF is fitted separately for each observed intervention. It first constructs a population-valued anchor using equal reference contribution and then applies a bounded coordinate-conditioned residual flow. On matched Perturb-map tasks, RADF reduces macro E-distance, an unordered-population distance, from 138.05 to 40.60 relative to CONCERT (70.6%) and from 62.98 for scGen to 40.60. Validation-gated residual refinement improves E-distance over the learned anchor by only 0.24% overall, indicating that reference anchoring provides the main gain while the flow supplies conservative refinement. Code will be made publicly available upon acceptance.