Evidence map›Paper›PMID 41497647›Full record

ArticlebioRxiv : the preprint server for biology2025

Application of Large Language Models for Annotating Genes into Reactome Pathways.

Guanming Wu, Lisa Matthews, Nathan Boyer, Marija Milacic, Deidre Beavers, Nancy T Li, Bruce May, Karen Rothfels, Veronica Shamovsky, Ralf Stephan and 4 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Guanming WuDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, United States.ORCID 0000-0001-8196-1177
Lisa MatthewsNYU Grossman School of Medicine, New York University, New York, NY 10016, United States.
Nathan BoyerDivision of Informatics, Clinical Epidemiology and Translational Data Science, Department of Medicine, Oregon Health and Science University, Portland, OR 97239, United States.
Marija MilacicOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Deidre BeaversDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, United States.
Nancy T LiOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Bruce MayOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Karen RothfelsOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Veronica ShamovskyNYU Grossman School of Medicine, New York University, New York, NY 10016, United States.
Ralf StephanOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.ORCID 0000-0002-4650-631X
Marc GillespieCollege of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, United States.
Henning HermjakobEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
Peter D'EustachioNYU Grossman School of Medicine, New York University, New York, NY 10016, United States.
Lincoln SteinOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Funding

Reactome: An Open Knowledgebase of Human Pathways.U24HG012198 · NHGRI · ONTARIO INSTITUTE FOR CANCER RESEARCH · PI Marc E Gillespie, LINCOLN D. STEIN · 2022 to 2026
$7.0M
Reactome and the Gene Ontology: Digital pathway convergence for core data resourcesU24HG011851 · NHGRI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DEUSTACHIO, PETER G, MUNGALL, CHRISTOPHER J · 2021 to 2025
$3.6M
Reactome IDG portal: Pathway-based analysis and visualization of understudied human proteinsU01CA239069 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DEUSTACHIO, PETER G, STEIN, LINCOLN D. · 2019 to 2021
$1.3M
NCI NIH HHS U01 CA239069NHGRI NIH HHS U24 HG011851NHGRI NIH HHS U24 HG012198
6 · The paper itself

Abstract

Reactome is the most comprehensive, open source, open access biological pathway knowledgebase, widely used in the research community. To ensure the highest quality of its content, human pathway data in Reactome is manually curated. However, manual curation is labor-intensive, time-consuming, and increasingly difficult to keep up with the ever-growing biomedical literature. Large language model (LLM)-driven artificial intelligence (AI) technologies are transforming many fields, including bioinformatics resource development. Applying LLM/AI technologies in Reactome may offer a powerful way to scale curation and consolidate pathway-related data into a single resource. This manuscript describes the first stage of our attempt to adopt LLM/AI technologies for Reactome manual curation. We developed an LLM workflow that can assist curators in adding new genes to existing pathways and refining the functional annotations of existing ones. The workflow predicts pathways in which genes are likely to function, identifies PubMed-indexed literature that may support these predictions, generates text summaries describing potential molecular mechanisms, and extracts functional relationships among biological entities from full-text PDF papers. To validate the workflow output, we used a computational approach based on semantic similarity between LLM workflow-generated summaries and Reactome manual annotations. The results show significant enrichment of high-similarity matches. Manual evaluation of 19 genes indicated that more than half of the outputs are useful for supporting curation. Based on these results, we developed an enhanced workflow that incorporates protein-protein interaction data, facilitating Reactome's reaction-based annotation. In summary, our initial adoption of LLM/AI technologies produced encouraging results and provides a practical framework for integrating AI-assisted methods into Reactome's curation pipeline. The strategies described here may be broadly applicable to community knowledgebases in general.

Identifiers

PMID41497647
PMCPMC12767520

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.