Controllable Sequence Editing for Biological and Clinical Trajectories

Abstract: Conditional generation models for longitudinal sequences can generate new or modified trajectories given a conditioning input. While effective at generating entire sequences, these models typically lack control over the timing and scope of the edits. Most existing approaches either operate on univariate sequences or assume that the condition affects all variables and time steps. However, many scientific and clinical applications require more precise interventions, where a condition takes effect only after a specific time and influences only a subset of variables. We introduce CLEF, a controllable sequence editing model for conditional generation of immediate and delayed effects in multivariate longitudinal sequences. CLEF learns temporal concepts that encode how and when a condition alters future sequence evolution. These concepts allow CLEF to apply targeted edits to the affected time steps and variables while preserving the rest of the sequence. We evaluate CLEF on 6 datasets spanning cellular reprogramming and patient health trajectories, comparing against 9 state-of-the-art baselines. CLEF improves immediate sequence editing accuracy by up to 36.01% (MAE). Unlike prior models, CLEF enables one-step conditional generation at arbitrary future times, outperforming them in delayed sequence editing by up to 65.71% (MAE). We test CLEF under counterfactual inference assumptions and show up to 63.19% (MAE) improvement on zero-shot conditional generation of counterfactual trajectories. In a case study of patients with type 1 diabetes mellitus, CLEF identifies clinical interventions that generate realistic counterfactual trajectories shifted toward healthier outcomes.