# Large Language Models for Zero-shot Inference of Causal Structures in Biology

arXiv: https://arxiv.org/abs/2503.04347 · HTML: https://mlsanity.com/paper/2503.04347/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 13 of its 32 references that are in the map.
- First posted on arXiv 6 Mar 2025.

## Builds on (most cited first, 13 of 13)

- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [GPT-4o System Card](https://mlsanity.com/paper/2410.21276/) (2024)
- [Gemma 2: Improving Open Language Models at a Practical Size](https://mlsanity.com/paper/2408.00118/) (2024)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Causal Reasoning and Large Language Models: Opening a New Frontier for Causality](https://mlsanity.com/paper/2305.00050/) (2023)
- [Causal Structure Learning](https://mlsanity.com/paper/1706.09141/) (2017)
- [MoCa: Measuring Human-Language Model Alignment on Causal and Moral Judgment Tasks](https://mlsanity.com/paper/2310.19677/) (2023)
- [PerturBench: Benchmarking Machine Learning Models for Cellular Perturbation Analysis](https://mlsanity.com/paper/2408.10609/) (2024)
- [PubTator 3.0: an AI-powered Literature Resource for Unlocking Biomedical Knowledge](https://mlsanity.com/paper/2401.11048/) (2024)
- [CausalBench: A Large-scale Benchmark for Network Inference from Single-cell Perturbation Data](https://mlsanity.com/paper/2210.17283/) (2022)
- [CRAB: Assessing the Strength of Causal Relationships Between Real-world Events](https://mlsanity.com/paper/2311.04284/) (2023)
- [Automating Exploratory Proteomics Research via Language Models](https://mlsanity.com/paper/2411.03743/) (2024)
- [Simulation-based Benchmarking for Causal Structure Learning in Gene Perturbation Experiments](https://mlsanity.com/paper/2407.06015/) (2024)

## Built on by (most cited first, 2 of 2)

- [LLM Cannot Discover Causality, and Should Be Restricted to Non-Decisional Support in Causal Discovery](https://mlsanity.com/paper/2506.00844/) (2025)
- [DMCD: Semantic-Statistical Framework for Causal Discovery](https://mlsanity.com/paper/2602.20333/) (2026)

## Abstract (arXiv)

Genes, proteins and other biological entities influence one another via causal molecular networks. Causal relationships in such networks are mediated by complex and diverse mechanisms, through latent variables, and are often specific to cellular context. It remains challenging to characterise such networks in practice. Here, we present a novel framework to evaluate large language models (LLMs) for zero-shot inference of causal relationships in biology. In particular, we systematically evaluate causal claims obtained from an LLM using real-world interventional data. This is done over one hundred variables and thousands of causal hypotheses. Furthermore, we consider several prompting and retrieval-augmentation strategies, including large, and potentially conflicting, collections of scientific articles. Our results show that with tailored augmentation and prompting, even relatively small LLMs can capture meaningful aspects of causal structure in biological systems. This supports the notion that LLMs could act as orchestration tools in biological discovery, by helping to distil current knowledge in ways amenable to downstream analysis. Our approach to assessing LLMs with respect to experimental data is relevant for a broad range of problems at the intersection of causal learning, LLMs and scientific discovery.