Louis-Félix Nothias

Matthieu Féraud, Dina Boukhajou, Fabien Gandon et al.

Untargeted metabolomics generates large volumes of tandem mass spectrometry (MS/MS) data and computational annotations that can reveal molecular mechanisms across organisms and environments. Public reuse has improved through harmonized repository metadata and access infrastructures such as Pan-ReDU, and through metabolomics knowledge graphs such as ENPKG and METRIN-KG. Yet the analytical layer remains fragmented: spectra, features, workflow outputs, annotations, confidence evidence, and contextual metadata are still scattered across repositories and tabular artifacts. We present MetaboKG, an analysis-centric knowledge graph framework for engineering reusable metabolomics knowledge from public repositories, metadata, and GNPS molecular network results. MetaboKG contributes a transformation workflow that preserves links between repository exports, analytical files, spectra, features, and annotation results; a semantic model grounded in PROV-O and SIO and aligned with the Mass Spectrometry ontology (MS), ChEBI, NCBITaxon, ENVO, and NCIT to represent provenance, analytical evidence, metadata attributes, and controlled vocabulary terms; and a Universal Annotation Identifier strategy extending the Universal Spectrum Identifier (USI) with workflow-specific components for late binding, incremental ingestion, and post hoc linkage across analyses. We demonstrate MetaboKG at the public-repository scale on 680 GNPS molecular networking results and evaluate it through competency questions covering biochemical enrichment, environmental specificity, and cross instrument analytical variation. Results show that graph-based integration supports traceable annotation reuse and reproducible SPARQL exploration of biochemical relationships that remain fragmented across repository-native resources.

Madina Bekbergenova, Lucas Pradi, Benjamin Navet et al.

Mass spectrometry metabolomics generates vast amounts of data requiring advanced methods for interpretation. Knowledge graphs address these challenges by structuring mass spectrometry data, metabolite information, and their relationships into a connected network (Gaudry et al. 2024). However, effective use of a knowledge graph demands an in-depth understanding of its ontology and its query language syntax. To overcome this, we designed MetaboT, an AI system utilizing large language models (LLMs) to translate user questions into SPARQL semantic query language for operating on knowledge graphs (Steve Harris 2013). We demonstrate its effectiveness using the Experimental Natural Products Knowledge Graph (ENPKG), a large-scale public knowledge graph for plant natural products (Gaudry et al. 2024).MetaboT employs specialized AI agents for handling user queries and interacting with the knowledge graph by breaking down complex tasks into discrete components, each managed by a specialised agent (Fig. 1a). The multi-agent system is constructed using the LangChain and LangGraph libraries, which facilitate the integration of LLMs with external tools and information sources (LangChain, n.d.). The query generation process follows a structured workflow. First, the Entry Agent determines if the question is new or a follow-up to previous interactions. New questions are forwarded to the Validator Agent, which verifies if the question is related to the knowledge graph. Then, the valid question is sent to the Supervisor Agent, which identifies if the question requires chemical conversions or standardized identifiers. In this case it delegates the question to the Knowledge Graph Agent, which can use tools to extract necessary details, such as URIs or taxonomies of chemical names, from the user query. Finally, an agent responsible for crafting the SPARQL queries equipped with the ontology of the knowledge graph uses the provided identifiers to generate the query. Then, the system executes the generated query against the metabolomics knowledge graph and returns structured results to the user (Fig. 1b). To assess the performance of MetaboT we have curated 50 metabolomics-related questions and their expected answers. In addition to submitting these questions to MetaboT, we evaluated a baseline by submitting them to a standard LLM (GPT-4o) with a prompt that incorporated the knowledge graph ontology but did not provide specific entity IDs. This baseline achieved only 8.16% accuracy, compared to MetaboT's 83.67%, underscoring the necessity of our multi-agent system for accurately retrieving entities and generating correct SPARQL queries. MetaboT demonstrates promising performance as a conversational question-answering assistant, enabling researchers to retrieve structured metabolomics data through natural language queries. By automating the generation and execution of SPARQL queries, it removes technical barriers that have traditionally hindered access to knowledge graphs. Importantly, MetaboT leverages the capabilities of LLMs while maintaining experimentally grounded query generation, ensuring that outputs remain aligned with domain-specific standards and data structures. This approach facilitates data-driven discoveries by bridging the gap between complex semantic technologies and user-friendly interaction. MetaboT is accessible at [https://metabot.holobiomicslab.eu/], and its source code is available at [https://github.com/HolobiomicsLab/MetaboT].

Yousouf Taghzouti, Franck Michel, Tao Jiang et al.

The SPARQL query language is the standard method to access knowledge graphs (KGs). However, formulating SPARQL queries is a significant challenge for non-expert users, and remains time-consuming for the experienced ones. Best practices recommend to document KGs with competency questions and example queries to contextualise the knowledge they contain and illustrate their potential applications. In practice, however, this is either not the case or the examples are provided in limited numbers. Large Language Models (LLMs) are being used in conversational agents and are proving to be an attractive solution with a wide range of applications, from simple question-answering about common knowledge to generating code in a targeted programming language. However, training and testing these models to produce high quality SPARQL queries from natural language questions requires substantial datasets of question-query pairs. In this paper, we present Q${}^2$Forge that addresses the challenge of generating new competency questions for a KG and corresponding SPARQL queries. It iteratively validates those queries with human feedback and LLM as a judge. Q${}^2$Forge is open source, generic, extensible and modular, meaning that the different modules of the application (CQ generation, query generation and query refinement) can be used separately, as an integrated pipeline, or replaced by alternative services. The result is a complete pipeline from competency question formulation to query evaluation, supporting the creation of reference query sets for any target KG.