PREFER: An Ontology for the PREcision FERmentation Community

Biomedical ontology normalization maps free-text expressions to standardized concepts, enabling consistent integration and analysis of biomedical data. This task remains challenging because lexical variation and subtle distinctions among hierarchically related concepts can obscure concept boundaries. We present OntologyAligner, a three-stage framework that combines ontology-aligned retrieval, large language model candidate reranking, and selective hierarchy-guided refinement. We also construct PhenoNormBench, a unified benchmark comprising 13,390 samples from seven Human Phenotype Ontology datasets. OntologyAligner achieved state-of-the-art performance on HPO normalization, with 88.78% Macro Top-1 Accuracy and 86.75% Micro Top-1 Accuracy, exceeding the strongest baseline by 4.85 and 5.07 percentage points, respectively. Ablation analyses showed complementary contributions from all three stages, and sensitivity analyses demonstrated stability across candidate-set sizes and model backbones. Applications to MONDO, MEDIC, and NCBITaxon further established portability to other ontologies. OntologyAligner offers a generalizable framework for accurate mapping of biomedical text to structured ontology concepts. PhenoNormBench and the code are publicly available at https://github.com/zhelishisongjie/OntologyAligner.

Designing microbial strains that produce high-value chemicals at commercially viable titers remains a central challenge in metabolic engineering. Existing computational approaches either rely on stoichiometric constraint-based models that cannot learn from experimental data, or apply tabular machine learning to hand-crafted features that discard the relational structure of biological knowledge. We present Canopy, a heterogeneous graph foundation model that integrates ten public and proprietary data sources into a unified knowledge graph (KG) of 6.9M nodes across 13 types and 34 edge types, covering genes, proteins, metabolites, reactions, pathways, strains, and fermentation experiments. Node features are encoded through domain-specific foundation models (ESM-2 for protein sequences, MoLFormer for chemical SMILES, and PubMedBERT for biomedical text), yielding a multi-modal representation within a single graph. We pretrain a Heterogeneous Graph Transformer (HGT) augmented with SignNet positional encodings, Jumping Knowledge aggregation, and virtual nodes using four self-supervised objectives (link prediction, masked node modelling, distance prediction, and contrastive experiment clustering), balanced via learned homoscedastic uncertainty weighting. On the downstream task of fermentation titer prediction, frozen Canopy embeddings achieve $R^{2} = 0.41$ with a lightweight probe, outperforming tabular baselines (best $R^{2} = 0.24$) and homogeneous GNN variants.

We present Open Ontologies, an open-source ontology engineering system implemented in Rust that integrates LLM-driven construction with formal OWL reasoning and ontology alignment via the Model Context Protocol. Our primary finding is that stable 1-to-1 matching is the dominant factor in ontology alignment quality: on the OAEI Anatomy track, it achieves F1 = 0.832 (P = 0.963, R = 0.733), competitive with state-of-the-art systems and exceeding all in precision. Ablation across five weight configurations shows that signal weights are irrelevant when stable matching is applied (F1 varies by less than 0.004), while removing stable matching drops F1 to 0.728. On the Conference track, the same method achieves F1 = 0.438. On tool-augmented ontology interaction, we find a surprising result: an LLM reading a raw OWL file (F1 = 0.323) performs worse than the same LLM with no file at all (F1 = 0.431), while structured MCP tool access achieves F1 = 0.717. This demonstrates that tool structure provides a qualitatively different mode of access that the LLM cannot replicate by reading raw syntax. The system ships as a single binary under the MIT licence.