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Jun 12

Towards generalizable single-cell perturbation modeling via the Conditional Monge Gap

Learning the response of single-cells to various treatments offers great potential to enable targeted therapies. In this context, neural optimal transport (OT) has emerged as a principled methodological framework because it inherently accommodates the challenges of unpaired data induced by cell destruction during data acquisition. However, most existing OT approaches are incapable of conditioning on different treatment contexts (e.g., time, drug treatment, drug dosage, or cell type) and we still lack methods that unanimously show promising generalization performance to unseen treatments. Here, we propose the Conditional Monge Gap which learns OT maps conditionally on arbitrary covariates. We demonstrate its value in predicting single-cell perturbation responses conditional to one or multiple drugs, a drug dosage, or combinations thereof. We find that our conditional models achieve results comparable and sometimes even superior to the condition-specific state-of-the-art on scRNA-seq as well as multiplexed protein imaging data. Notably, by aggregating data across conditions we perform cross-task learning which unlocks remarkable generalization abilities to unseen drugs or drug dosages, widely outperforming other conditional models in capturing heterogeneity (i.e., higher moments) in the perturbed population. Finally, by scaling to hundreds of conditions and testing on unseen drugs, we narrow the gap between structure-based and effect-based drug representations, suggesting a promising path to the successful prediction of perturbation effects for unseen treatments.

  • 4 authors
·
Apr 11, 2025

TeamBench: Evaluating Agent Coordination under Enforced Role Separation

Agent systems often decompose a task across multiple roles, but these roles are typically specified by prompts rather than enforced by access controls. Without enforcement, a team pass rate can mask whether agents actually coordinated or whether one role effectively did another role's work. We present TeamBench, a benchmark with 851 task templates and 931 seeded instances for evaluating agent coordination under operating system-enforced role separation. TeamBench separates specification access, workspace editing, and final certification across Planner, Executor, and Verifier roles, so that no role can read the full requirements, modify the workspace, and certify the final answer. Prompt-only and sandbox-enforced teams reach statistically indistinguishable pass rates, but prompt-only runs produce 3.6 times more cases where the verifier attempts to edit the executor's code. Verifiers approve 49% of submissions that fail the deterministic grader, and removing the verifier improves mean partial score in the ablation. Team value is also conditional. Teams benefit when single agents struggle, but hurt when single agents already perform well. A 40-session human study under the same role separation shows that our benchmark exposes interaction patterns that pass rate misses. Solo participants work through the task directly, human participants paired with agents often collapse into quick approval, and human teams spend more effort coordinating missing information across roles.

  • 12 authors
·
May 7