# TSAssistant: A Human-in-the-Loop Agentic Framework for Automated Target Safety Assessment

arXiv: https://arxiv.org/abs/2604.23938 · HTML: https://mlsanity.com/paper/2604.23938/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 32 of its 78 references that are in the map.
- First posted on arXiv 27 Apr 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 32)

- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [Judging LLM-as-a-Judge with MT-Bench and Chatbot Arena](https://mlsanity.com/paper/2306.05685/) (2023)
- [BERTScore: Evaluating Text Generation with BERT](https://mlsanity.com/paper/1904.09675/) (2019)
- [Reflexion: Language Agents with Verbal Reinforcement Learning](https://mlsanity.com/paper/2303.11366/) (2023)
- [Generative Agents: Interactive Simulacra of Human Behavior](https://mlsanity.com/paper/2304.03442/) (2023)
- [Tree of Thoughts: Deliberate Problem Solving with Large Language Models](https://mlsanity.com/paper/2305.10601/) (2023)
- [G-Eval: NLG Evaluation using GPT-4 with Better Human Alignment](https://mlsanity.com/paper/2303.16634/) (2023)
- [AutoGen: Enabling Next-Gen LLM Applications via Multi-Agent Conversation](https://mlsanity.com/paper/2308.08155/) (2023)
- [MetaGPT: Meta Programming for A Multi-Agent Collaborative Framework](https://mlsanity.com/paper/2308.00352/) (2023)
- [FActScore: Fine-grained Atomic Evaluation of Factual Precision in Long Form Text Generation](https://mlsanity.com/paper/2305.14251/) (2023)
- [The AI Scientist: Towards Fully Automated Open-Ended Scientific Discovery](https://mlsanity.com/paper/2408.06292/) (2024)
- [Semantic Uncertainty: Linguistic Invariances for Uncertainty Estimation in Natural Language Generation](https://mlsanity.com/paper/2302.09664/) (2023)
- [SelfCheckGPT: Zero-Resource Black-Box Hallucination Detection for Generative Large Language Models](https://mlsanity.com/paper/2303.08896/) (2023)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Accelerating scientific discovery with Co-Scientist](https://mlsanity.com/paper/2502.18864/) (2025)
- [ReConcile: Round-Table Conference Improves Reasoning via Consensus among Diverse LLMs](https://mlsanity.com/paper/2309.13007/) (2023)
- [Generating with Confidence: Uncertainty Quantification for Black-box Large Language Models](https://mlsanity.com/paper/2305.19187/) (2023)
- [MDAgents: An Adaptive Collaboration of LLMs for Medical Decision-Making](https://mlsanity.com/paper/2404.15155/) (2024)
- [Long-form factuality in large language models](https://mlsanity.com/paper/2403.18802/) (2024)
- [Towards a Science of Scaling Agent Systems](https://mlsanity.com/paper/2512.08296/) (2025)
- [PromptChainer: Chaining Large Language Model Prompts through Visual Programming](https://mlsanity.com/paper/2203.06566/) (2022)
- [The Ethics of Advanced AI Assistants](https://mlsanity.com/paper/2404.16244/) (2024)
- [MAM: Modular Multi-Agent Framework for Multi-Modal Medical Diagnosis via Role-Specialized Collaboration](https://mlsanity.com/paper/2506.19835/) (2025)
- [MedAgentBoard: Benchmarking Multi-Agent Collaboration with Conventional Methods for Diverse Medical Tasks](https://mlsanity.com/paper/2505.12371/) (2025)
- [ToolUniverse: An open platform for democratizing AI scientists](https://mlsanity.com/paper/2509.23426/) (2025)
- [ColaCare: Enhancing Electronic Health Record Modeling through Large Language Model-Driven Multi-Agent Collaboration](https://mlsanity.com/paper/2410.02551/) (2024)
- [EMERGE: Enhancing Multimodal Electronic Health Records Predictive Modeling with Retrieval-Augmented Generation](https://mlsanity.com/paper/2406.00036/) (2024)
- [LLMs Corrupt Your Documents When You Delegate](https://mlsanity.com/paper/2604.15597/) (2026)

## Abstract (arXiv)

Target Safety Assessment (TSA) requires systematic integration of genetic, transcriptomic, target homology, pharmacological, and clinical data to evaluate potential safety liabilities of therapeutic targets. This process is labor-intensive and expert-dependent, posing challenges in scalability and reproducibility. We present TSAssistant, a human-in-the-loop multi-agent framework that decomposes TSA report generation into a workflow of specialized subagents: Research Subagents that each ground and cite a single TSA domain, and Synthesis Subagents that integrate findings across domains. Subagents retrieve and synthesize evidence from curated biomedical sources through standardized tool interfaces and produce individually citable, evidence-grounded sections, with behavior shaped by a hierarchical instruction architecture that separates coordination logic from domain expertise and user intent. To complement these soft constraints, programmatic execution hooks and persistent memory stores enforce hard constraints across the workflow, while an interactive refinement loop allows experts to review and revise individual sections with full conversational context preserved across iterations. Rather than a single holistic comparison, we decompose report quality into reproducibility, evidential grounding, task-level accuracy, and controllability under expert oversight, finding high reproducibility and grounding, substantial agreement with the human reference, and net-positive expert-driven refinement.