Thought Graph: Generating Thought Process for Biological Reasoning

We present the Thought Graph as a novel framework to support complex reasoning and use gene set analysis as an example to uncover semantic relationships between biological processes. Our framework stands out for its ability to provide a deeper understanding of gene sets, significantly surpassing GSEA by 40.28% and LLM baselines by 5.38% based on cosine similarity to human annotations. Our analysis further provides insights into future directions of biological processes naming, and implications for bioinformatics and precision medicine.

Evaluation of large language models for discovery of gene set function

Gene set analysis is a mainstay of functional genomics, but it relies on manually curated databases of gene functions that are incomplete and unaware of biological context. Here we evaluate the ability of OpenAI's GPT-4, a Large Language Model (LLM), to develop hypotheses about common gene functions from its embedded biomedical knowledge. We created a GPT-4 pipeline to label gene sets with names that summarize their consensus functions, substantiated by analysis text and citations. Benchmarking against named gene sets in the Gene Ontology, GPT-4 generated very similar names in 50% of cases, while in most remaining cases it recovered the name of a more general concept. In gene sets discovered in 'omics data, GPT-4 names were more informative than gene set enrichment, with supporting statements and citations that largely verified in human review. The ability to rapidly synthesize common gene functions positions LLMs as valuable functional genomics assistants.