# GRASP: Graph Reasoning Agents for Systems Pharmacology with Human-in-the-Loop

arXiv: https://arxiv.org/abs/2512.05502 · HTML: https://mlsanity.com/paper/2512.05502/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 11 of its 27 references that are in the map.
- First posted on arXiv 5 Dec 2025.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)
- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 11 of 11)

- [Multi-Agent Collaboration Mechanisms: A Survey of LLMs](https://mlsanity.com/paper/2501.06322/) (2025)
- [MedRAG: Enhancing Retrieval-augmented Generation with Knowledge Graph-Elicited Reasoning for Healthcare Copilot](https://mlsanity.com/paper/2502.04413/) (2025)
- [DrugAgent: Automating AI-aided Drug Discovery Programming through LLM Multi-Agent Collaboration](https://mlsanity.com/paper/2411.15692/) (2024)
- [MMedAgent-RL: Optimizing Multi-Agent Collaboration for Multimodal Medical Reasoning](https://mlsanity.com/paper/2506.00555/) (2025)
- [CodeJudge-Eval: Can Large Language Models be Good Judges in Code Understanding?](https://mlsanity.com/paper/2408.10718/) (2024)
- [Human-in-the-loop or AI-in-the-loop? Automate or Collaborate?](https://mlsanity.com/paper/2412.14232/) (2024)
- [KGARevion: An AI Agent for Knowledge-Intensive Biomedical QA](https://mlsanity.com/paper/2410.04660/) (2024)
- [GCoT: Chain-of-Thought Prompt Learning for Graphs](https://mlsanity.com/paper/2502.08092/) (2025)
- [K-Paths: Reasoning over Graph Paths for Drug Repurposing and Drug Interaction Prediction](https://mlsanity.com/paper/2502.13344/) (2025)
- [Collaborative Intelligence in Sequential Experiments: A Human-in-the-Loop Framework for Drug Discovery](https://mlsanity.com/paper/2405.03942/) (2024)
- [MAGIC: Multi-Agent Argumentation and Grammar Integrated Critiquer](https://mlsanity.com/paper/2506.13037/) (2025)

## Abstract (arXiv)

Quantitative Systems Pharmacology (QSP) modeling is essential for drug development but it requires significant time investment that limits the throughput of domain experts. We present GRASP -- a multi-agent, graph-reasoning framework with a human-in-the-loop conversational interface -- that encodes QSP models as typed biological knowledge graphs and compiles them to executable MATLAB/SimBiology code while preserving units, mass balance, and physiological constraints. A two-phase workflow -- textscUnderstanding (graph reconstruction of legacy code) and textscAction (constraint-checked, language-driven modification) -- is orchestrated by a state machine with iterative validation. GRASP performs breadth-first parameter-alignment around new entities to surface dependent quantities and propose biologically plausible defaults, and it runs automatic execution/diagnostics until convergence. In head-to-head evaluations using LLM-as-judge, GRASP outperforms SME-guided CoT and ToT baselines across biological plausibility, mathematical correctness, structural fidelity, and code quality ((≈)9--10/10 vs. 5--7/10). BFS alignment achieves F1 = 0.95 for dependency discovery, units, and range. These results demonstrate that graph-structured, agentic workflows can make QSP model development both accessible and rigorous, enabling domain experts to specify mechanisms in natural language without sacrificing biomedical fidelity.