Medical Ontology

Published medical case reports serve as a crucial medical information carrier, documenting discoveries in rare diseases, diagnostic methods, and innovative treatments. Despite the wealth of clinical knowledge in millions of case reports in the public medicine literature database (PubMed), accessing relevant information efficiently is hindered by the limitations of traditional keyword-based retrieval tools on unstructured and diverse case reports. To address the above issues, we introduce a comprehensive multimodal information system for case reports integrating structured clinical summaries of patients including medical images and biomedical named entities from 52949 open-access case reports published from 2000 to 2021. The multimodal essential information is organized in a well-structured medical ontology. Also, a powerful interface for searching and browsing case reports is designed to assist junior clinicians in retrieving cases effectively and improving the identification and diagnosis of rare diseases.

Biomedical knowledge graphs combine ontology-derived hierarchies with transversal associations among heterogeneous entities such as phenotypes, diseases, genes, proteins, and patients. This hybrid structure raises the question of whether hyperbolic embeddings, which naturally capture tree-like organization, remain useful beyond purely hierarchical graphs. We present a preliminary study of hyperbolic graph representation learning for Mendelian-disease differential diagnosis on a patient-integrated biomedical graph. Experiments on isolated ontology subgraphs show that hyperbolic models achieve strong performance in substantially lower dimensions than Euclidean baselines. We then evaluate the models on a link-prediction task that ranks candidate diseases for each patient. Results suggest that hyperbolic embeddings can exploit biomedical hierarchical structure while supporting diagnostic reasoning over heterogeneous patient-level graphs.

Large language models (LLMs) can generate biomedical hypotheses, but it remains unclear whether they truly reason from scientific evidence or simply produce convincing-sounding ideas. To study this, we combine three major biological databases: the Kyoto Encyclopedia of Genes and Genomes (KEGG), Rhea, and UniProt, into a unified biochemical knowledge graph and construct a benchmark of 550 paths connecting enzyme sources to rare disease endpoints, yielding 13,200 hypotheses from six LLMs under four conditions varying the biological information each model receives: source enzyme only, full biological path, or source and disease endpoint only. Hypotheses are scored using an expert-derived five-criterion rubric on a 1-5 scale per criterion. We find that models given both the source and disease endpoint often produce the highest-scoring hypotheses, showing that LLMs can generate compelling ideas from minimal information. However, these hypotheses are less grounded in the evidence. In contrast, models given the full biological path generate hypotheses more consistent with known mechanistic relationships. We call this evidence-disciplined reasoning. To confirm this effect, we shuffled intermediate path steps while keeping endpoints fixed. Evidence grounding dropped significantly (delta = -0.793, p < 0.001), confirming models genuinely used path structure during reasoning. Our findings show that knowledge graphs support hypothesis generation in two ways: they identify biological endpoint pairs absent from the literature, and their mechanistic paths guide how LLMs reason between them.

Background. Large language models are increasingly used to help write biomedical text but may fabricate references to nonexistent work. How often large language models do so is not well characterized. Methods. We prompted 26 language models from eight developers (2023 to 2026) to supply a missing reference for each of 69 biomedical passages across ten domains. References were classified as verifiable (real paper with a resolving identifier), partial matches (real paper without a resolving identifier), fabricated (no matching indexed paper), or declined (the model refused to supply a reference). A reference was considered correct in every evaluated bibliographic field only when it was verifiable and its journal, year, and listed authors matched those of the cited paper. Results. Fabrication ranged from 10.2% (Claude Opus 4.8, which declined 52.1% of prompts) to 98.4% (Ministral 3B, which produced no verifiable reference). Claude Opus 4.6 and Claude Sonnet 4.5 produced similar proportions of verifiable references (77.6% and 76.6%) but named authors correctly in 78.7% and 28.7% of author-evaluable verifiable references, respectively, and were correct in every evaluated field in 54.6% and 19.9% of responses. GPT-5.5 was correct in every field in 48.1%. Across all models, 55.4% of responses were fabricated and 14.9% were correct in every field. Among the five tested models first released in 2026, the corresponding proportions were 35.3% and 31.8%, respectively. Conclusions. Fabrication remained common, and no model was correct in every evaluated bibliographic field in more than 54.6% of responses. Models that identify real papers may still misstate their metadata, so references produced with model assistance require verification before use.

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.

We introduce OntologyBench, a tiered biomedical retrieval benchmark comprising 471,854 training and 125,744 evaluation query-document relevance pairs across concept grounding, relational retrieval, and compositional phenotype-based retrieval. Although these tasks can be tractable using ontology-aware reference methods, across task tiers, embedding performance is generally lower on relational and compositional tasks than on concept-grounding tasks. Fine-tuning on ontology-derived supervision improves performance on several relational and compositional tasks, whereas the evaluated reranking and LLM-based candidate-scoring methods provide little or no end-to-end improvement. Errors frequently reflect diseases matching only subsets of the phenotype evidence. These findings indicate that the evaluated embedding and reranking configurations do not reliably recover the compatibility encoded by the selected ontology relations and phenotype combinations and motivate retrieval systems that better integrate learned representations with structured biomedical knowledge.

Background. Large language models (LLMs) are being adopted in biomedical research at a rapid and accelerating pace, yet commercial services that host many widely used models operate under deprecation schedules that can complicate scientific reproducibility. Methods. We searched PubMed for original research articles from 2022 through March 2026 that applied a specific LLM to a biomedical task. An extraction agent identified model names from 61,077 article abstracts with human reviewers validating a subset for extraction accuracy. Extracted model names were normalized to canonical model identifiers. Lifecycle data (release date, retirement date, status) were compiled for the 50 most frequently used models. Results. We identified 8,931 paper-model mentions spanning 5,242 unique publications after restricting the analysis to the 50 most frequently used models. Among these mentions, 77.7% cited a commercial closed-weight model. Overall, 42% involved a model that was already retired by the time of official publication or is scheduled to retire within two years of publication. The median interval from publication to model retirement was 538 days. Conclusion. Many biomedical publications using LLMs are on a trajectory toward computational non-reproducibility after publication. Model deprecation should be treated as a core reporting and preservation issue for biomedical research.

Many biomedical challenges can be posed as tensor completion problems where the observed entries of a multidimensional array (a tensor) are used to impute the missing values. In such settings, incorporating side information about the modes of the tensor, such as gene-gene similarity, can significantly enhance the solutions of the completion problem. Most existing tensor completion methods can only incorporate side information in the form of matrices. In this study, we introduce a novel framework to incorporate side information in the form of tensors. Our new approach, called Coupled Tensor-Tensor Completion (CTTC), leverages the hidden connections among multimodal tensors to improve tensor completion performance. In addition to practical utility, CTTC has theoretical foundations in distance metric learning and group theory. We derive an alternating algorithm to solve the CTTC optimization problem and establish its convergence to a stationary point. Finally, we show that CTTC outperforms state-of-the-art tensor completion methods at predicting drug effects. Results: Compared with other tensor completion methods, including HaLRTC, CTRC, Cell, and NTDDR, CTTC demonstrates superior run-time and RSE tensor completion accuracy on two benchmark datasets, DTD and LINCS.

Vision-Language Pretrained Models (VLPMs) offer a scalable path to open-vocabulary chest radiology understanding, yet two aspects remain underexplored: how structured clinical semantics extracted from medical reports can reduce in-batch noise during contrastive learning, and how cross-modal fusion can be designed to produce more faithful spatial grounding without added complexity. We introduce AlphaRAD, addressing these opportunities through two contributions. First, we construct a large-scale structured medical concept space from medical reports parsed by a Large Language Model for training, thereby mitigating in-batch learning noise and removing heuristic pair matching in contrastive learning, and thus naturally positioning AlphaRAD as a medical concept discriminator trained via $α$-Corrected Binary Cross-Entropy. Second, we propose FLaS (Factorized Latent Supervision), an extremely simple yet effective cross-modal feature fusion module that factorizes VLPM representations into independent subspaces, using dedicated alignment supervision to enhance the expressiveness of spatial grounding without introducing additional model parameters. Through extensive empirical validation, AlphaRAD shows strong zero-shot generalization across diverse chest radiology tasks. Notably, it establishes state-of-the-art average performance across 16 classification benchmarks, while achieving individual state-of-the-art results via distinct gains on 7 grounding/phrase grounding and 3 segmentation datasets.

Scientific domain entity linking (EL) differs from general domain EL because mentions and entity names often lack lexical overlap. Another challenge is that specialized terminology is used in the scientific domain, which is rarely encountered in models pretrained on general domains. Therefore, models trained on general domains transfer poorly to scientific domains. To address this, in-domain fine-tuning is the natural remedy. However, many scientific domains lack expert-annotated data, motivating the need for a zero-human-annotation approach. Existing zero-shot methods heavily rely on LLMs to generate aliases across entire mention corpora, which incurs substantial computational cost, and those methods provide no mechanism to filter out noise from LLMs. To address these challenges, we propose Sci-ZSEL, a framework that selectively generates entity aliases with an LLM to control computational cost, and applies an ontology-aware filter to remove aliases that semantically drift toward ontology neighbors. Then, filtered aliases are used to construct pseudo-labeled mention-entity pairs for fine-tuning. To enable evaluation of EL under low lexical overlap, we also release a new animal science EL benchmark linked to three livestock trait ontologies, where mentions and entities exhibit substantially lower lexical overlap than in existing benchmarks. Across five benchmarks, Sci-ZSEL outperforms the non-fine-tuned baseline, is most useful on nonoverlapping mentions, and combining it with curated synonyms gives the best performance in most settings.

BioMedRAG introduced retrieval-augmented generation with a learned chunk scorer for biomedical information extraction. However, it relies on fixed-size chunking which can fragment semantic evidence. We propose a configurable semantic chunking framework that addresses this limitation by combining entity-preserving windows, trigger-centered chunking, proposition-first extraction, tiered trigger prioritization, and hierarchical relation resolution. The framework integrates with BioMedRAG by replacing only the chunk construction stage while preserving the embedding model, learned chunk scorer, generator, and evaluation protocol. We evaluate the framework on biomedical relation extraction benchmarks (GM-CIHT, DDI, ChemProt) and adverse event classification (ADE). On GM-CIHT, the full hybrid configuration achieves 82.6% F1, improving over the fixed-size baseline (74.2% F1) by 8.4 points under our experimental setup. Cross-dataset analysis shows that semantic chunking improves extraction datasets with explicit relation cues, such as GM-CIHT and DDI, while fixed chunking remains competitive or stronger for dense biochemical extraction and binary classification settings such as ChemProt and ADE. By externalizing chunking logic into configuration files, the framework provides an interpretable and adaptable alternative to rigid fixed-size chunking for biomedical RAG pipelines.

Artificial intelligence (AI) and natural language processing (NLP) are increasingly used to extract, integrate, and interpret biomedical knowledge relevant to cancer genomics, yet their translation into routine clinical oncology has been comparatively slow. The central challenge is not computational capability alone, but trustworthy integration into clinical workflows. This review examines how NLP and AI support the cancer genomics pipeline, from literature mining and automated variant interpretation to clinical trial matching, knowledge graph construction, and multimodal data integration. We identify four interrelated translational failure domains: evidence inconsistency, explainability and uncertainty, data governance and reproducibility, and interoperability. Rather than considering these challenges in isolation, we take a systems-level view, focusing on their interaction across the translational pathway. We propose a conceptual framework and roadmap for addressing these domains through rigorous validation, uncertainty-aware methods, interoperable infrastructures, regulatory alignment, and human oversight across the AI lifecycle. Progress toward routine clinical use will depend less on further improving model capability than on systematically addressing these interacting failure domains from development through deployment and post-deployment monitoring.

Path-finding over knowledge graphs has become an effective way to ground LLM reasoning on multi-hop questions. However, biomedical QA introduces two distinct challenges that general-domain methods are not designed for: (i) queries do not expose intermediate reasoning and can be answered through multiple valid pathways, and (ii) biomedical knowledge graphs are densely connected, so path-finding methods easily take wrong turns. To address these challenges, we propose AdaPath, a path-finding framework that retrieves query-adaptive meta-paths from Path-Bank, which captures both query semantics and biomedical knowledge graph structure. AdaPath provides the missing cues in biomedical queries while effectively pruning dense knowledge graph neighborhoods during multi-hop reasoning. We further release BioStrat-QA, a biomedical KGQA benchmark that stratifies multi-hop queries by how much intermediate reasoning they expose. Across biomedical KGQA benchmarks, AdaPath consistently outperforms baselines, sustaining meaningful path-finding even when multi-hop queries expose less surface information. The source code is available at https://github.com/Jun-Hyeong-Kim/AdaPath.

Biomedical artificial intelligence (AI) systems increasingly extract, organize, and reuse scientific claims from literature, clinical trials, and regulatory documents. But automatic extraction alone does not make a claim reliable evidence: a claim becomes useful only when it can be traced to its source, linked to the quantitative details that support it, and read within its biomedical context and uncertainty. This matters as large language models (LLMs) and increasingly autonomous systems drive evidence synthesis, knowledge graph (KG) construction, and decision support. Many text-mining and LLM pipelines remain relation-centric: they capture entities and relations such as Drug--TREATS--Disease, but drop the dose, effect size, population, comparator, uncertainty, and conditions under which a claim holds. Such relations can look actionable yet remain hard to verify, compare, or reuse. In this perspective, we argue for a shift toward quantitative evidence mining---extracting values, units, measured entities and properties, context, uncertainty, provenance, and plausibility as structured evidence units that populate evidence-aware KGs and can be checked for source grounding, unit consistency, completeness, and biological plausibility. We outline a framework for plausibility-aware AI that treats extracted claims not as final answers but as auditable evidence objects, making clear what was measured, how much it changed, in which setting, with what uncertainty, and from which source. The central risk is not only incorrect extraction, but claims that look like evidence while lacking the structure needed to trust them.

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing \emph{when} and \emph{after which events} risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. Evaluated on 57,078 MIMIC-IV admissions against GRU-D, STraTS, and KarmaLego, INTERVenE-Enc reaches a support-weighted AUPRC$_w$ of 0.672, improving by 0.041 over the strongest neural baseline with non-overlapping 95% bootstrap CIs, while also taking the best AUROC$_w$ (0.901) and length-of-stay MAE (44.4,h). INTERVenE-Ar (AUROC$_w$ $0.854$, AUPRC$_w$ $0.587$ under the same evaluation contract - a strictly harder generative readout) provides a complementary token-level risk trajectory. An input-representation ablation confirms the lift transfers across structured discretizations, positioning KBTA-based intervals as the interpretable substrate that makes per-token attributions resolve to meaningful clinical concepts within the deployed model.

Biomedical Named Entity Recognition (NER) is fundamental to healthcare AI applications, including clinical decision support and medical information extraction. While corpora with Unified Medical Language System (UMLS) annotations, such as MedMentions, have driven progress in English biomedical NER, no comparable resource exists for Vietnamese. This paper presents En-ViMedNER, the first English-Vietnamese parallel biomedical NER corpus annotated with UMLS semantic types, which are language-neutral codes providing a shared cross-lingual label space and ensuring direct comparability with existing UMLS-based resources. The corpus contains 4,392 PubMed abstract pairs, 44,892 English-Vietnamese sentence pairs, and 202,949 aligned entity-mention pairs across 21 semantic types adapted from the MedMentions ST21pv dataset. To balance quality and scalability, we have constructed the corpus through automatic translation, expert post-editing, LLM-assisted label projection, and human verification and adjudication. We characterize En-ViMedNER as a large-scale silver-standard corpus with a human-audited and consensus-corrected mini-test subset. We evaluate En-ViMedNER in two settings: (i) Vietnamese-input/Vietnamese-output biomedical NER and (ii) English-input/Vietnamese-output cross-lingual NER. For Vietnamese NER, we benchmark Vietnamese-supervised encoder models, English-supervised multilingual encoder models, and prompt-based LLMs. The best model achieves an F1 score of 52.70 on the test set and 53.78 on the mini-test set. For cross-lingual NER, we benchmark encoder-decoder models and prompt-based LLMs. The best model achieves an F1 score of 45.44 on the mini-test set. We publicly release our corpus, corpus construction pipeline, and baseline models to facilitate future Vietnamese biomedical NLP research.

Over the past several years, LLM-powered chatbots and agents have become widely used as a tool for academic writing. LLM-assisted writing can be valuable by removing language barriers but at the same time causes concerns about misconduct and fraud. To inform policy decisions, it is necessary to monitor the prevalence of LLM-altered texts in scholarly publications. Despite some recent progress in this direction, no existing method can produce reliable estimates. Here we suggest and validate a new unbiased approach to estimate LLM usage in a corpus of texts based on changing word frequencies. We apply our method to the full texts of open-access biomedical papers from Pubmed Central, and show that by the end of 2025, 89% of papers show excess of LLM-associated vocabulary. We also find that LLMs are twice as likely to be used when writing a paragraph in the Discussion section (68%) compared to a paragraph in the Methods section (32%), but even inside the Methods section, the overall prevalence of LLM usage is over 50%. We believe that our estimates are crucial to shape future guidelines and policies.

Biomedical knowledge graphs (KGs) accelerate drug discovery, but standard pipelines assume query molecules already exist as graph entities, leaving unregistered molecules disconnected. We address this cold-start challenge, termed the out-of-graph molecule problem, by introducing MolBioKG. This two-layer system grounds unseen molecules in biomedical evidence via multi-resolution structural anchoring. It connects an index of 2.74 million molecules (represented by scaffolds, fragments, functional groups, and fingerprints) to a 9.6-million-edge KG. Given only a SMILES string, MolBioKG retrieves structurally related graph entities and traverses their biomedical neighborhoods without task-specific training. It features two inference mechanisms: static multi-anchor retrieval using Reciprocal Rank Fusion, and Adapt-KG, a tool-using LLM policy for adaptive traversal. Evaluated across in-graph link recovery, complex multi-hop reasoning, and out-of-graph generalization, MolBioKG outperforms strong baselines. Notably, it raises Hits@10 from 0.585 to 0.876 in multi-hop reasoning and out-of-graph target recall from 0.145 to 0.269, all while ensuring predictions retain traceable structural anchors and source-attributed KG evidence.

Metabolomics knowledge is distributed across heterogeneous resources and remains difficult to translate into predictive representations. We developed MetaboLLM, a metabolomics-specialized large language model adapted through continual pretraining, supervised fine-tuning, and structured retrieval, together with MetaboLLM-GIN, which converts generated biochemical descriptions into metabolite graphs for patient-level prediction using a graph isomorphism network. Across four backbone families, MetaboLLM outperformed corresponding base and medically adapted models on metabolomics knowledge, relational, and description tasks, and transferred to an external public benchmark. MetaboLLM-GIN achieved the highest AUC for stress hyperglycemia prediction after coronary artery bypass grafting (0.8616) and postmenopausal hormone-regimen classification (0.8123), outperforming conventional models, alternative graph constructions, and graphs generated from unadapted or non-retrieval LLM configurations. Model interpretation further produced biologically meaningful findings in both applications. These results show that domain-specialized language models can organize heterogeneous biochemical knowledge into predictive and interpretable metabolite graph representations.

We describe Research Assistant, an internal LLM-based system developed at AstraZeneca to help scientists and clinicians explore biomedical questions across a broad range of data sources. The system provides a chat-style interface that brings together evidence from scientific literature, knowledge graphs, chemistry, clinical trials, safety resources, expression data, and internal experimental systems. It supports both a fast mode for direct question answering and a multi-step mode for more complex research tasks. Responses are grounded in retrieved evidence and linked back to the original sources, allowing users to review and further explore the underlying data. In this technical note, we outline the system architecture, the main design choices behind the product, and lessons learned from deploying it at scale to support day-to-day R&D workflows across AstraZeneca.

Inadequate target--disease linkage accounts for 40--50% of PhaseII efficacy failures, so anticipating which programmes will advance would let sponsors back the hypotheses most likely to reach patients. What a programme can be judged on is the evidence that supported its linkage \emph{when it entered the clinic}. No existing biomedical knowledge graph allows that evidence profile to be assembled as of a past date. We present the Temporal Heterogeneous Biomedical Knowledge Graph (THBKG), which describes and predicts therapeutic target--disease links through time: 110,396 entities and 11.1M edges across nineteen relation types, each edge carrying the year its evidence changed, so a pair's profile can be recovered as it stood when its own decision fell due. On this graph we define a decision-aligned benchmark that predicts, for a target--disease pair entering PhaseII, whether it advances to Phase~III on evidence datable before that decision. Graph propagation over the THBKG outranks every direct-evidence reference scored under the same decision-aligned protocol, reaching a relative success of 4.3--4.5 at the top ten pairs per therapeutic area. The gain concentrates on the 72.8% of pairs with no direct target--disease evidence at their decision point, where a direct-edge model has nothing to read: the encoders still rank five- to sixfold above chance, recovering the signal by propagating over the intervening biology. Adapting a path-based explainer to the decision-time subgraph decomposes each prediction into the evidence landscape behind the hypothesis for explainable prediction. We release the THBKG as a continually updated substrate for studying therapeutic target hypotheses by retrospective validation.

Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes. Here we present BioM-JEPA, a joint-embedding predictive architecture that instead predicts aggregate representations of graph-connected gene blocks defined by protein-association and corpus-derived coexpression evidence. A student network infers each target-block representation from the remaining genes in a cell, while a slowly updated teacher supplies the corresponding target from the full observed gene set. Under the reported extraction procedure, block-level prediction produced embeddings with higher effective rank and weaker association with detected-gene depth in the tested diagnostics than token-prediction, random-block and reconstruction controls. Across CellBench tasks, frozen BioM-JEPA embeddings retained expression, pathway and neighbourhood information and achieved the lowest aggregate perturbation-response error among the evaluated models. Representation diagnostics were also consistent with canonical pancreatic programmes and compositional relationships between genetic perturbations. Linear attention avoids constructing a quadratic gene-by-gene attention matrix; in a matched one-epoch hPancreas experiment at batch size 8, BioM-JEPA provided 5.75-fold higher fine-tuning throughput and 3.76-fold higher held-out embedding throughput than scFoundation. Together, these results support graph-connected gene blocks as useful prediction units for JEPA-style representation learning in single-cell biology.

Biomedical entity linking grounds mentions in clinical and scientific text to entities in a curated knowledge base (KB) with ontological structure, which supports downstream applications such as literature-scale information extraction and patient-record normalization. The task has several challenges at once: the KB contains large numbers of entities, mentions are often ambiguous, and gold labels follow annotation conventions specific to each corpus. To address these challenges, we propose PILOT, a three-stage framework made up of neighborhood-aware retrieval, dual reranking, and score fusion. The retriever injects ontological structure from both the query and KB side, by reformulating mentions and pooling entity embeddings. The retrieved pool is then scored from two complementary views, one over surface forms and one over context, and fused together. PILOT achieves the state of the art on average across five widely-used benchmarks and remains efficient at inference.

Biomedical literature is increasingly mined for knowledge beyond the questions it was written to answer. Because the target concepts are not known in advance, annotators prefer open-ended labels, whose agreement is hard to quantify. We study soft inter-rater reliability for annotators providing unstructured texts for biomedical annotation tasks. Synthetic experiments show that soft reliability can be quantified using a variety of semantic equivalence measures, and that the choice of measure affects failure modes of the estimation. Embeddings are scalable, but limited when differentiating similar but distinct concepts. Large language models are promising, but limited by scalability for estimating agreement by chance. Finally, we suggest measures based on natural language inference as a sensible compromise.

Biomedical fact-checking systems must do more than predict whether a claim is supported, contradicted, or unaddressed: they should also produce evidence that is faithful, complete, and useful for verification. We study this evidence-generation setting on CARE-XAI, a unified benchmark spanning five biomedical and health fact-checking sources. We compare base instruction LLMs, PubMed retrieval-augmented LLMs, fine-tuned LLMs, label-only LLMs, and biomedical encoder classifiers under a shared evaluation protocol. Biomedical classifiers remain strongest for verdict-only prediction, while fine-tuned LLMs are the strongest evidence-generating systems. PubMed retrieval is mixed: it helps PubMed-aligned sources such as PubMedQA and SciFact, but can distract models on broader public-health claims. We introduce Bio-GRACE, a gold-reference-normalized diagnostic for measuring whether retrieved evidence recovers the decision benefit of reference evidence. Bio-GRACE shows that retrieval utility is source-dependent, motivates selective retrieval, and exposes why retrieval recall and lexical evidence overlap are insufficient for biomedical fact-checking.

Phenotype-driven diagnostic benchmarks usually report the rank of the reference disease, but they rarely reveal which plausible alternatives are ranked above it or what evidence a tool-using model examines before making its decision. We introduce GraphRareBench, a provenance-preserving benchmark containing 2,365 ontology-derived cases and 18,093 target-confounder pairs. Each case includes a coarsened HPO query, a fixed candidate pool, graph-defined hard confounders, and source-linked evidence records. On the 237-case gene-component-disjoint test split, supervised rankers using a shared 21-feature interface achieved MRRs ranging from 0.640 to 0.740 and case-averaged target-over-confounder accuracies ranging from 0.898 to 0.916. Agents instantiated with Agents-A1 and DeepSeek-V4-Flash achieved MRRs of 0.746 and 0.718, respectively. Their paired MRR difference was not statistically significant, whereas their target-evidence coverage differed by 0.561. Together with the observation that 22.1% to 43.7% of selected Hit@10 successes still ranked at least one graph-defined hard confounder above the target, these results indicate that full-pool retrieval, hard-confounder discrimination, and observable evidence access capture complementary aspects of model behavior. GraphRareBench therefore provides a foundation for more transparent and evidence-aware evaluation of phenotype-driven diagnostic systems. Code and data are available at https://github.com/GUI0609/GraphRareBench.

Constructing causal directed acyclic graphs (DAGs) is a core step in biomedical causal analysis, yet it remains a largely manual process. Analysts must connect study variables to prior literature, evaluate uncertain causal claims, and preserve sufficient provenance for expert review. We present EviDAG, a browser-based system for authoring causal DAGs as auditable, evidence-linked artifacts from biomedical literature. Given free-text descriptions of study concepts, EviDAG creates a reproducible literature snapshot, uses an LLM-based reasoning module to generate structured pairwise causal judgments, links literature-supported judgments to verbatim evidence excerpts, and assembles the judgments into a constraint-checked graph. Each proposed edge includes confidence estimates, provenance, and a reviewable rationale. The interface supports study specification, progress monitoring, evidence review, graph comparison, adjustment-set computation, and export. In evaluations against both compact benchmark DAGs and reference DAGs derived from published literature, EviDAG achieves high edge recall on the literature-based cohort while retaining verifiable evidence trails absent from LLM-only baselines. EviDAG thus reduces the burden of causal DAG curation while making the resulting assumptions auditable, supporting the design, analysis, and interpretation of biomedical studies.

The rapid growth of biomedical knowledge has made the validation of automatically generated biological annotations a major bottleneck in biomedical curation. While computational methods can rapidly produce large numbers of candidate annotations, determining which are biologically valid still requires costly expert review. Prioritizing these candidates before manual curation has therefore become a fundamental challenge. Machine learning techniques can support this process by exploiting biomedical knowledge graphs (bioKGs), which capture biological entities and their functional associations. In this work, we propose a framework that leverages bioKGs to estimate the plausibility of candidate annotations and guide expert curation. Starting from knowledge graph embeddings, we train relation-specific binary classifiers using a community-based negative sampling strategy to obtain reliable confidence estimates. We then introduce a family of plausibility measures that combine classifier confidence, classifier reliability, and the semantic context provided by alternative relationships involving the same pair of biological entities. Unlike conventional confidence estimation, the proposed approach explicitly accounts for multiple biologically meaningful relations that may coexist between the same entities. Experimental results on five large bioKGs demonstrate that the proposed negative sampling strategy consistently improves classifier robustness, increasing balanced accuracy by an average of 5.8%. Moreover, the plausibility measures outperform classifier confidence alone, enabling more effective prioritization of candidate annotations for expert review. Overall, our results show that the use of bioKGs improves the efficiency of AI-assisted biomedical curation while preserving expert control over the final annotation assessment.

We present OntoBook, a method that converts medical ontology structure into pretraining signal for encoder language models. Our approach has three stages: random walks through ontology graphs capture hierarchical and causal relations between medical codes, a large language model reformulates these walks into fluent textbook-style prose, and the resulting text is used to train ModernCamemBERT, a 149M-parameter French encoder, with two objectives on the same data: masked language modeling and relation prediction between code pairs. On three French medical coding benchmarks (FRACCO, Cantemist-FR, Distemist-FR), OntoBook achieves significant improvements over MLM-only pretraining, with +2.5 micro-F1 on FRACCO and +8.0 micro-F1 on Distemist. We find that alignment between objectives is necessary: misaligned training, where each task uses different data, causes a 30-point degradation. We release 1.3 million LLM-reformulated medical textbooks across three French ontologies (CIM-10, CCAM, ATC) and pretrained model checkpoints.

Knowledge Organization Systems like Ontologies and taxonomies are fundamental for structuring scientific knowledge, yet their manual curation presents a persistent bottleneck in knowledge management. While Large Language Models (LLMs) offer a scalable mechanism for automated ontology generation, their capacity to classify complex, domain-specific semantics requires systematic evaluation. In this paper, we assess the performance of five small, open-source LLMs (up to 9 billion parameters) in identifying semantic relationships between biomedical concepts. To support this evaluation, we introduce MeSH-Rel-4K, a dataset comprising 4K semantic relationships extracted from the Medical Subject Headings (MeSH). We analyse three adaptation strategies: standard prompting, Chain-of-Thought prompting, and fine-tuning. While parameter-constrained models traditionally struggle with the nuances of in-context logic, our results reveal that targeted fine-tuning increases the average F1-score by 34.1 percentage points. These results confirm that direct fine-tuning effectively exceeds the reasoning bottlenecks of smaller LLMs, providing an accurate, automated methodology for the construction and evolution of specialised biomedical ontologies.

Inferring gene regulatory networks (GRNs) from single-cell transcriptomic data is crucial for biological discovery, yet existing approaches suffer from a fundamental misalignment with real-world needs. Researchers typically seek a small set of high-confidence regulatory interactions for experimental validation, often involving previously unseen genes. However, current benchmarks rely on transductive splits with global classification metrics, while prevailing models struggle to generalize under inductive settings. To bridge this gap, we reformulate GRN inference as an inductive, ranking-centric graph completion problem and introduce \textbf{\benchmark}, a new benchmark that incorporates an inductive gene-holdout split together with knowledge graph completion metrics to better evaluate top-ranked predictions. Building on this, we propose \textbf{\method}, the first co-evolutionary discrete diffusion framework that jointly models biologically coherent discretized gene expression states and regulatory interactions for robust inductive generalization and improved top-ranked regulatory discovery. We further introduce TF-ALL Subgraph Sampling (TASS) for scalable training. Extensive experiments on {\benchmark} show that {\method} establishes new state-of-the-art performance, significantly outperforming existing methods in novel regulatory discovery, and ablation studies further verify the effectiveness of our design.

Retrieval-Augmented Generation (RAG) addresses the limitations of Large Language Models (LLMs) when providing responses to domain-specific questions. Graph-based RAG approaches, such as GraphRAG, enhance retrieval by capturing semantic relationships within knowledge graphs (KGs). While the FAIR principles (Findability, Accessibility, Interoperability, and Reusability) are becoming prevalent for scientific data management, especially in complex domains such as medicine, existing RAG approaches lack a structured FAIRification of the underlying knowledge resources. This lack limits their potential for FAIR information retrieval in these domains. To address this gap, we introduce FAIR GraphRAG, a novel framework that integrates FAIR Digital Objects (FDOs) as the fundamental units of a graph-based retrieval system. Each graph node represents an FDO that incorporates core data, metadata, persistent identifiers, and semantic links. We leverage LLMs to support schema construction and automated extraction of content and metadata from data sources. The framework was co-designed by physicians and computer scientists to ensure technical and clinical relevance. We apply FAIR GraphRAG to a biomedical dataset in gastroenterology, demonstrating its applicability to RNA-sequencing data. Beyond ensuring adherence to the FAIR principles, FAIR GraphRAG significantly improves question answering accuracy, coverage, and explainability, particularly for complex queries involving metadata and ontology links. This work shows the feasibility of combining FAIR data practices with graph-based retrieval techniques. We see potential for applying our approach to other specialized fields such as education and business.

Biomedical language evolves rapidly as new discoveries emerge, causing traditional text models to lose semantic fidelity over time. Static embeddings and co-occurrence graphs cannot capture such evolution, leading to performance degradation in retrieval and knowledge discovery tasks. This paper introduces a Drift-Aware Temporal Graph Rewiring (DATGR) framework that models concept evolution by dynamically updating co-occurrence edges based on estimated semantic drift. Instead of retraining embeddings for each time slice, DATGR performs lightweight, feedback-driven rewiring using a logistic update rule applied to edge weights. Evaluated on the Biomedical Multi-Relation Corpus (BIOMRC), the method achieved a mean Area Under the Receiver Operating Characteristic (AUROC) improvement of approximately 0.066 absolute difference (0.699 vs. 0.633) over a static baseline. Area Under the Precision-Recall Curve (AUPRC) remained comparable (0.738 vs. 0.744), showing that drift-aware adaptation enhances link-prediction recall without a loss in precision. These results demonstrate that edge-level adaptation effectively captures temporal semantic change in evolving biomedical text while remaining computationally efficient and interpretable.

Biomedical question answering requires not only accurate extraction of information from scientific literature but also reliable integration of evidence across multiple documents. This study presents a question-type-specific large language model (LLM) framework for BioASQ 14b Task B, designed to improve answer robustness and evidence grounding in biomedical question answering. Rather than applying a single prompting strategy to all questions, the framework selects different inference procedures for yes/no, factoid, and list questions according to their distinct reasoning and evaluation requirements. For yes/no questions, snippet shuffling and self-reflection are used to reduce sensitivity to evidence ordering and improve decision stability. For factoid questions, full-snippet input is combined with chain-of-thought-based in-context learning to support accurate biomedical entity identification. For list questions, a multi-agent architecture is employed, in which evidence extraction, candidate generation, answer verification, and final aggregation are handled collaboratively. Preliminary experiments on BioASQ 13b were used to identify effective inference strategies for each question type, and the resulting framework was subsequently evaluated in the official BioASQ 14b Task B challenge. In the official evaluation, our framework showed competitive performance across multiple batches and achieved first place in the factoid subtask of Batch 4. These results demonstrate the effectiveness of combining question-type-specific inference, ensemble prediction, and agent-based verification for reliable biomedical question answering.

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.

Glaucoma is a leading cause of irreversible blindness worldwide, yet most automated diagnosis systems rely on opaque deep-learning models that offer little clinical interpretability. We present GlaKG, a biomarker-centric fundus knowledge graph that integrates structural biomarkers, clinically grounded rules, and image features to produce traceable reasoning for glaucoma diagnosis and risk stratification. GlaKG encodes six entity types (Fundus Image, Optic Disc, Neural Rim, Pathology, Diagnosis, Risk Level), eight relation types, and 11 clinically validated rules into a unified graph, so that every prediction is accompanied by an explicit reasoning chain linking biomarker evidence to activated clinical rules. To keep knowledge-based reasoning strictly separate from label information, we adopt a post-processing fusion framework that combines ResNet50 image embeddings with a normalized KG reasoning-chain score via a tunable weight alpha, with all fitting confined to the training split. On a publicly available, AI-annotated fundus dataset, GlaKG reaches F1 = 0.9953 for binary glaucoma classification and 0.930 accuracy with 0.922 weighted F1 for four-class risk stratification; we report openly that the dataset's biomarker annotations are highly label-correlated, and therefore frame these figures as an upper bound attainable with clean structured biomarkers rather than as leakage-free image-only performance. Feature-importance analysis shows KG-derived and biomarker features contributing near-equally (51.1% vs. 48.9%), and the reasoning chain flags borderline cases by exposing low chain scores rather than failing silently. GlaKG's central contribution is therefore a clinically auditable reasoning framework that complements raw predictive performance by explicitly exposing the biomarker evidence and rule activations behind each decision.

Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics. We propose PREDIKTOR, a patient-centered multi-view framework that aligns a personalized network view with a transferable transcriptomic perturbation view to predict clinical drug response. For each patient, we construct an individualized gene regulatory network from tumor expression using DysRegNet and augment it with drug-target links from DrugBank; a graph neural encoder yields a drug-centric, mechanistically grounded embedding. In parallel, a frozen condition-specific gene-gene attention model pretrained on LINCS L1000 generates a simulated post-perturbation transcriptomic profile for the same patient-drug pair. We align the two views in a shared latent space via a CLIP-style contrastive objective with drug-context hard negatives, then concatenate the representations for end-to-end response classification. On TCGA, PREDIKTOR consistently outperforms state-of-the-art baselines under patient-, drug-, and tissue-split evaluations, and transfers zero-shot to the I-SPY2 trial, improving AUROC by 5.6% over competing methods. The aligned embeddings yield stable gene and pathway attributions that recover known mechanisms, supporting actionable and interpretable precision oncology.

Cold-start drug-drug interaction (DDI) prediction for new drugs is critical for minimizing unexpected adverse drug reactions. The key challenge is to capture similarity between new and known drugs. However, such similarity is closely associated with complex relationships and mechanisms among drugs, enzymes, transporters, molecular structures, and other biomedical entities. Existing methods have three limitations in capturing such similarity: (1) only partial relationships and mechanisms are considered, which overlooks cross-modal information and yields incomplete or biased similarity modeling; (2) similarity computation between new and known drugs is conducted separately across modalities and performed offline for cold-start DDI prediction, leading to misalignment between similarity computation and DDI prediction; and (3) existing interpretability analyses are typically single-modality and focus primarily on key determinants of the perpetrator drug, while the underlying causes of susceptibility for the victim drug are seldom investigated. To address these issues, this paper proposes a novel Cross-Modal-Fused End-to-End Learning Network (CMF-ELN) with three components. First, diverse multimodal information is leveraged to construct four types of drug-centered knowledge graphs, enabling comprehensive similarity modeling under reconstruction-based supervision. Second, a four-channel graph autoencoder is designed to fuse cross-modal similarity within an end-to-end learning framework. Finally, a two-stage interpretability scheme is devised to precisely localize key factors for both perpetrator and victim drugs. Extensive experiments on two real datasets demonstrate that CMF-ELN achieves significantly higher prediction accuracy and more comprehensive interpretability of mechanisms than its peers.

Accurate protein-protein interaction (PPI) prediction is central to functional genomics, disease mechanism discovery, and drug development. A difficult setting arises when candidate interactions include proteins that have no observed PPI edges during training, where models relying on network topology alone often lose useful context. This paper presents \method, a multimodal representation framework for cold-start PPI prediction. \method\ combines region-aware protein sequence encoding with four protein-centered biomedical knowledge graphs, including protein-drug, protein-disease, protein-miRNA, and protein-lncRNA associations. The sequence branch extracts contextual representations from structurally informed sequence regions, while graph attention encoders learn modality-specific protein embeddings from sparse biomedical associations. A bridge reconstruction objective regularizes graph learning by recovering shared protein-entity associations, and a pair-level gating module adaptively integrates sequence and graph evidence for each candidate protein pair. Experiments on two benchmark datasets under novel-old and novel-novel cold-start settings show that \method\ consistently outperforms competitive sequence, network, and knowledge-graph baselines across ACC, F1, AUC, AUPR, and MCC.

Current molecular generation benchmarks emphasize task complexity, molecule novelty, and property alignment; they largely overlook a critical concern: the potential safety risks of AI-generated molecules. In practice, many generative models may produce molecules with toxic, reactive, or otherwise hazardous characteristics - posing hidden dangers that remain insufficiently addressed. To address this gap, we introduce MolSafeEval, a benchmark dedicated to evaluating and analyzing the safety risks of molecular generation. Unlike prior approaches that rely on narrow toxicity predictors, MolSafeEval integrates heterogeneous safety knowledge - ranging from toxicological databases to hazard rules - into a structured molecular safety knowledge graph. This graph serves as a foundation for large language model-based reasoning, enabling systematic detection and explanation of unsafe features in generated compounds. We further categorize molecular generative models into four representative task types - unconditional generation, property optimization, target protein-based design, and text-based generation - and provide standardized datasets and safety evaluation protocols for each. By systematically revealing the safety vulnerabilities of current generative approaches, MolSafeEval offers a new lens for benchmarking molecular models and provides essential guidance toward safer, more trustworthy molecular design.

Acquiring comprehensive cross-domain biomedical profiles is often costly and time-consuming, resulting in severe data scarcity in medical research. To address this challenge, we propose MedKGTab, a knowledge-injected framework specifically engineered for cross-domain feature expansion in tabular medical data. MedKGTab seeks to infer uncollected biomedical features from available ones by exploiting their inherent statistical dependencies and established medical correlations. By employing a row-column dual-attention mechanism, MedKGTab operates directly on raw structured tabular data, inherently capturing exact numerical distributions without the structural loss caused by tokenization. Crucially, MedKGTab integrates data-driven statistical priors with the SPOKE biomedical knowledge graph, achieving an optimal synergy between the data and knowledge channels. Within this synergy, the representations derived from the data channel are modulated by the injected biomedical knowledge, ensuring the final generated data are grounded in empirical medical research. Experimental results demonstrate that MedKGTab achieves high data fidelity and realistic data representation in cross-domain feature expansion. It outperforms both SOTA medical large models (e.g., Baichuan M3-plus) and specialized tabular models designed for medical data generation. Furthermore, MedKGTab consistently delivers superior performance across various data generation scenarios, whether inferring missing features within the same dataset or generalizing across different medical cohorts.

Automatic mapping between disease classification systems, such as the International Classification of Diseases (ICD), is a challenging yet essential task for integrating health data and conducting longitudinal data analysis. Existing embedding-based methods primarily focus on \emph{one-to-one} mappings, overlooking more complex \emph{one-to-many} scenarios. The threshold-based and top-K methods offer natural extensions; however, they involve inherent trade-offs between \emph{precision}, \emph{recall} and \emph{mapping coverage} -- the proportion of source codes with at least one mapping to a target code. To address this challenge, we introduce a novel method, which is inspired by the \emph{blocking-and-matching} pipeline commonly used in \emph{entity resolution}. In particular, we first generate a block of candidate matches (\emph{blocking}) and then employ a large language model (LLM) to identify all valid mappings within each block (\emph{matching}). Empirically, we show that the proposed method achieves higher precision with comparable recall and broader coverage across multiple ICD version pairs (ICD-9-CM$\leftrightarrow$ICD-10-CM and ICD-10-AM$\leftrightarrow$ICD-11). Our source code and dataset is available at: https://tinyurl.com/46kyn7wp.

While WGS-based AMR prediction has reached high accuracy, existing models lack a mechanism to ground neural attributions in established biological pathways. We present KG-TRACE, a novel neuro-symbolic framework that integrates the WHO mutation knowledge graph (KG) as a structured biological constraint on a neural genomic model. Unlike existing methods that learn statistical patterns in isolation, KG-TRACE fuses genomic features and RotatE-based KG embeddings through a learned epistemic trust gate, dynamically weighting neural evidence against symbolic biological knowledge. Evaluated on the CRyPTIC M. tuberculosis cohort, KG-TRACE achieves an AUROC of 0.9760 for isoniazid, achieving competitive accuracy while its primary value lies in symbolic grounding, not predictive uplift. More importantly, we introduce the Biological Grounding Ratio (BGR), a dataset-level metric that quantifies alignment between neural attributions and established biology. Our framework achieves a 92.5% symbolic coverage of isoniazid-resistant predictions and effectively identifies MDR co-occurrence artifacts by issuing laboratory follow-up flags for 'UNCERTAIN' cases. We demonstrate that neuro-symbolic grounding provides a verifiable audit trail for clinicians, bridging the gap between predictive accuracy and clinical trust.

Scientific long-document summarization datasets commonly treat author-written abstracts as gold reference summaries, although their quality and alignment with the source article vary. At the same time, publicly available scientific summarization datasets remain limited in scale and structure for modern long-context models. In this work, we address both challenges by a) constructing and releasing one of the largest biomedical and life science datasets for long-document summarization, containing 1.88 million PMC articles, and b) analyzing the reference quality of author-written abstracts with source-grounded and model-based metrics. We show that author-written abstracts vary in their alignment with the full article and that these quality signals can guide training-data selection. Training on selected high-quality subsets outperforms random sampling at matched training sizes and can match or exceed larger random subsets on factuality-oriented metrics. Our findings suggest that reference quality is an important factor in scientific summarization and that quality-aware data selection can improve training efficiency.

Predicting transcriptional responses to genetic perturbations could reduce the experimental burden of functional genomics, but extrapolation to genes that were never perturbed during training remains difficult. We present Stable-Shift, a structured method for estimating unseen-gene responses. Stable-Shift aggregates single-cell measurements into perturbation-level expression shifts, fits a low-rank response basis using training perturbations only, and predicts an unseen gene's coordinates in that basis from biological context. The context combines STRING interactions, network structure, control-cell expression statistics, and Gene Ontology annotations; the evaluated implementation uses graph convolution to integrate these inputs. On the supplied K562 Perturb-seq benchmark, Stable-Shift obtained 0.592 cosine similarity, compared with 0.569 for GEARS, together with higher Spearman correlation and top-gene precision among the evaluated methods. Its mean cosine similarity over five unseen-gene splits was 0.589 +/- 0.008. The same ordering was observed in the supplied graph-aware, residualized, gene-space, and Norman-dataset comparisons. These results support further study of biologically structured latent-response prediction, while the lower gene-space accuracy and sensitivity to sparse graph neighborhoods limit the scope of the present conclusions.

Hallucinations and opaque reasoning remain unacceptable failure modes for clinical LLMs. We present a production-grade GraphRAG stack that constrains answers to verifiable graph chain-of-thought paths in a heterogeneous, ~700K-node medical knowledge graph powering a fertility assistant. The core idea is targeted navigation: a directed Pruned Landmark Labeling (PLL) oracle provides exact distances for sub-millisecond feasibility checks and simple-path enumeration, while a lightweight AStarNet heuristic operates strictly within the PLL corridor to prioritize clinically plausible expansions. We score and pack a small, diverse set of paths (CUI/semantic-type overlap, length prior, provenance priors) to condition generation, yielding compact prompts and improved Time to First Token (TTFT). On fertility-focused queries, the hybrid (PLL+AStarNet) establishes a better latency/recall Pareto frontier than text-only RAG and single-component baselines, lowers TTFT, and reduces clinician-audited hallucinations while preserving explanation clarity. The result is a practical recipe for explainable, low-hallucination multi-hop medical reasoning ready for real-world deployment.

Objective: This study aims to improve the reliability and robustness of medical named entity recognition (NER) in Chinese atopic dermatitis (AD) clinical texts through explanation-guided learning. Methods: We propose a stability and boundary-aware explanation-guided NER framework. Perturbation-based analysis is used to evaluate explanation stability and entity boundary sensitivity. An adaptive fusion strategy dynamically combines local and global explanation to generate more reliable token-level explanations. The fused explanation signals are further incorporated into model training through stability, boundary-aware, and consistency constraints. Results: Experiments on Chinese AD NER datasets show that the proposed framework improves explanation robustness and achieves consistent performance gains across multiple NER models. The adaptive fusion strategy also provides more stable explanations and stronger boundary perception than individual explanation methods. Conclusion: The proposed method effectively integrates reliable explanation signals into medical NER training, improving both recognition performance and explanation reliability. The framework provides a practical and generalizable solution for explainable medical NER and offers reliable support for downstream clinical decision-making and medical knowledge applications.

A working citation looks like proof -- but the fact that a link resolves does not mean the cited paper supports the claim. I find that current agentic models rarely fabricate citations (over $99\%$ resolve), yet roughly $15.9\%$ link to the wrong paper. Existing benchmarks miss this failure mode: when a question has a fixed answer key, a model can reproduce the expected source from that key rather than independently verifying that the source supports the claim. I introduce \textbf{\openbiorq{}}, a retrieval-grounded agentic benchmark of $12{,}553$ unsolved biomedical research questions across $12$ domains that treats open questions as a faithfulness-and-abstention probe. To my knowledge, this is the first biomedical benchmark to combine an agentic setting -- where the model must issue multiple tool calls -- with unsolved questions that have no answer key. Openness is verified against real follow-up evidence rather than a model's parametric knowledge. Difficulty is empirical: I anchor it on questions that three open-weight reference models fail to answer, rather than on subjective hardness labels. On this hardest subset, held-out models from the same lineage as the difficulty anchors solve only ~17%, while three independent frontier agents (Gemini-3-Pro, Opus-4.7, GPT-5.5) span a wide 29-60% range. The benchmark is thus hard, non-saturating (the best agent still leaves ~33-40% unsolved), and discriminating across capability tiers. Beyond difficulty, I observe agentic collapse on the hardest questions, where agents stop using their tools. For the most collapse-prone model, blocking tool access entirely barely changes its score -- so tools stop paying off exactly where they are needed most. A frozen per-question checklist raises inter-judge agreement from Spearman 0.35 to 0.82.

Biomedical researchers increasingly use AI-generated analyses and reports to interpret protein-level signals, but static outputs are often insufficient for research decision-making, where users need to inspect evidence, assess uncertainty, compare mechanisms, and refine hypotheses. We present \textsc{BioInsight}, a multi-agent system that moves from static biomedical report generation to interactive evidence-centered interactive interface generation. Given a disease name, a protein association table, and optional cohort metadata, BioInsight organizes disease-specific evidence through typed intermediate artifacts, including ranked pathways, literature evidence packets, protein-level reasoning notes, citation-grounded reports, dashboard schemas, and rendered interactive interfaces. The system decomposes evidence retrieval from mechanistic reasoning, normalizes citations through deterministic components, and converts the same structured evidence used in the report into an interactive interface. We evaluate BioInsight on standardized biomedical QA, challenging protein-function reasoning, and end-to-end biomedical evidence synthesis. Results show that BioInsight achieves best, and suggest that biomedical AI systems should move beyond text-only and static reports toward provenance-preserving, interactive evidence artifacts.

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.

Historical medical archives and traditional medicines hold immense potential for drug discovery and remain a primary source for current drug development. However, pre-ontological prose and idiosyncratic taxonomies prevent the standardization and medical modernization of the data for use in current biomedical pipelines. Furthermore, no existing LLM agent system, whether tool-calling, retrieval-augmented, or agentic deep-research, can convert such text into verifiable drug-discovery leads at scale. We close this gap with DeepRoot, a multi-agent LLM system that jointly builds and utilizes a verified knowledge graph, showing that grounding and reasoning -- often conflated -- are separable axes the system can compose for therapeutic reasoning. Applied to the Shen Nong Ben Cao Jing, DeepRoot recovers $10$ of $21$ held-out compound-disease treatment pairs at R@$20$ ($47.6\%$ vs $4.8\%$ for a raw corpus LLM and $\sim\!2.4\%$ random) and dominates an LLM-as-judge audit for reasoning quality over baseline LLMs and LLMs with direct tool-call access to the same APIs DeepRoot itself queries. Tool-using LLMs hallucinate evidence on $87\%$ of claims, versus 7-10% for DeepRoot. Graph-only inference hallucinates $0\%$ but ranks lowest on reasoning coherence; DeepRoot KG+LLM is the only condition to win on both axes, pointing toward a route for systematic mining and repurposing of historical medical knowledge.

Interpretability is essential for trustworthy medical image diagnosis. However, existing concept-driven interpretable methods have key limitations: Concept Bottleneck Models (CBMs) require scoring all predefined concepts at inference time and for manual intervention, imposing a substantial burden on clinicians, while rationale-based generative approaches often select concepts by class discriminability, which can drift from diagnostic ontologies. To address these issues, we propose Neuro-Symbolic Rule Distillation (NeRD), a framework that produces efficient, ontology-grounded reasoning chains that are sufficient yet non-redundant, without manually crafting diagnostic rules. Experiments on two skin datasets demonstrate strong diagnostic performance and interpretability, and blinded expert evaluation confirms the clinical plausibility of NeRD rationales. Our method further enables a first expert-in-the-loop study for Multimodal Chain-of-Thought-based diagnosis, achieving efficient and effective concept-level intervention.

Electronic prior authorization workflows require FHIR Questionnaire items to carry LOINC codes, yet most items in the HL7 Da Vinci CDS-Library lack these bindings. We treat this as a retrieval problem: given a Questionnaire item's text, find the correct LOINC code in a pool of 97,314 active codes. We compare six methods (TF-IDF, frozen MiniLM, BioBERT, BioLORD, contrastively fine-tuned MiniLM, and a TF-IDF+GPT reranker) on a 54-item evaluation set spanning three query styles (natural question, medium, and terse). No single method wins on every metric. BioLORD, a frozen encoder pre-trained on biomedical ontology definitions, has the best top-rank accuracy (R@1 = 0.185, MRR = 0.246) despite seeing no task-specific data, while a contrastive fine-tune on raw LHC-Forms pairs takes R@5 (0.389) and R@10 (0.426). A distribution-shift ablation shows why the fine-tune in our main table is not the strongest one: adding GPT-generated paraphrases to the raw pairs drops R@5 from 0.389 to 0.296, so the augmented union underperforms raw-only training on every metric except R@1. Performance peaks at 5k training pairs. Error analysis on BioLORD's R@1 failures shows that wrong-specificity and ambiguous-text cases together account for 59% of errors.

Knowledge graphs (KGs) have emerged as a promising solution for integrating and reasoning over complex biomedical and clinical data in healthcare. By representing structured relationships among entities such as diseases, drugs, symptoms, and patient records, KGs provide a semantic backbone for decision-making, prediction, recommendation, and personalized care. Recent advances have demonstrated their utility across diverse medical applications--including clinical decision support systems, disease and treatment outcome prediction, health recommender systems, precision medicine, and medical question answering--where KGs often enhance interpretability, semantic coherence, and patient-specific reasoning. In parallel, a growing body of work focuses on medical KG generation itself, proposing frameworks that construct graphs from EHRs, clinical narratives, biomedical literature, and web resources using ontologies, semantic web technologies, deep-learning-based information extraction, and hybrid neuro-symbolic pipelines. Despite this progress, significant challenges remain, including limited and fragmented knowledge coverage, difficulties in aligning heterogeneous data sources, the fragility of current reasoning and representation-learning methods on dense multi-relational graphs, and unresolved issues related to privacy, bias, and accountability. This survey reviews and categorizes current research on KGs in medicine along both application-oriented and methodology-oriented dimensions, discusses their benefits and technical foundations, and outlines key limitations and open research directions. By analyzing trends, architectures, and evaluation practices, this work aims to guide future developments in KG-driven medical AI systems and support their safe and effective integration into healthcare environments.

Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug-disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings.

Structured abstracts are important for biomedical literature processing, by facilitating information retrieval, text mining, and knowledge synthesis. However, a vast portion of abstracts indexed in PubMed remain unstructured, presenting a significant bottleneck for downstream text-processing workflows and applications. To resolve this limitation, we introduce Structured PubMed, a comprehensive corpus of section-labeled biomedical abstracts compiled from the complete PubMed database, encompassing over 23.2 million research-article records. The corpus is divided into two distinct subsets: a collection of 5.9 million author-structured abstracts parsed from official XML files, and an automatically labeled collection of 17.2 million originally unstructured abstracts structured via a verbatim-extraction Large Language Model pipeline. Every record is harmonized under a unified five-section schema and mapped to its original PubMed identifier, publication type, and publication date. This dataset can be utilized to train sentence-classification models, benchmark text-segmentation architectures, and perform large-scale, section-specific information extraction at an unprecedented PubMed-wide scale.

In this investigation, we delve into the automated detection of speculative language within biomedical articles by utilizing distributed sentence representations and advanced deep learning techniques. The implications of such identification extend to information retrieval, multi-document summarization, and the exploration of new knowledge. Our exploration encompasses two distinct approaches for acquiring distributed sentence representations: the Paragraph Vector model and the Recursive Neural Tensor Network. These methodologies are then rigorously compared against three foundational baseline algorithms: Support Vector Machines, Naive Bayes, and pattern matching. Our findings reveal that the Recursive Neural Tensor Network (RNTN) demonstrates a slight performance edge (F1 = 0.885) over the top-performing baseline, the linear bigram SVM (F1 = 0.881). Meanwhile, the Paragraph Vector model proves less effective (F1 = 0.368), even after extensive training using an expansive, unlabeled dataset. We engage in a comprehensive discourse on the factors influencing these performance disparities and provide insightful recommendations for future research directions.

Biomedical text mining, scientometrics, and the construction of training corpora for biomedical large language models (LLMs) all assume that the abstract text returned by a bibliographic API faithfully reproduces the published abstract. This pre-registered audit (OSF osf.io/269b5) tests that assumption for four widely used public APIs (PubMed E-utilities, Crossref, OpenAlex, Semantic Scholar) against PubMed Central (PMC) JATS XML as a common ground truth. From a complete enumeration of the PMC Open Access subset for 2024 (about 700,000 records), a simple random sample of 4,000 English-language research articles was drawn; for each, we recorded whether Unicode characters from four pre-specified classes present in the JATS abstract (typographic punctuation, mathematical/scientific symbols, Greek letters, special whitespace) were preserved by each API. Two systematic, deterministic losses met the pre-registered criterion (upper 95% CI bound below 5%): the PubMed AbstractText field preserved typographic punctuation in only 0.6% of eligible abstracts (95% CI 0.3-1.0%), and OpenAlex preserved special whitespace in 0% (0.0-0.4%). A blinded mechanism audit attributed the first loss to character substitution and the second to inverted-index serialization. Mathematical symbols and Greek letters were preserved faithfully (over 95%) by all four APIs. Separately, Crossref returned no abstract for 24.6% of papers (coverage 75.4%, 95% CI 74.1-76.7%), concentrated in specific publishers (Elsevier and ACS: 0%). Character-level fidelity is therefore API-dependent and undocumented: the same publisher-deposited JATS text carries different surface signatures depending on the serving API, with direct consequences for tokenization-sensitive bibliometrics, corpus construction, and character-level indicators of LLM-assisted writing.

Predicting the effect of an unseen gene knockout perturbation on transcriptomic gene expression remains a highly challenging problem for virtual cell models. Recent progress has been made by leveraging biological knowledge graphs to provide a notion of similar perturbation, allowing for improved extrapolation beyond the set of training perturbations. In this work, we demonstrate that the simplest model to leverage these assumptions - a K-nearest neighbour from the knowledge graph - achieves highly competitive performance on this task, and that this can be improved further using LLMs optimised via reinforcement learning (RL) for predictive performance. Specifically, we find that the K-nearest neighbour approach beats almost all methods on out-of-distribution perturbation prediction, and when a reasoning LLM is trained via RL to make changes to the neighbourhood, it obtains equivalent performance to current state of the art methods on the cell lines from Replogle et al. (2022). We also demonstrate that the RL training improves the LLM's performance on the downstream task of differential expression prediction, despite not being trained on this directly. Overall, these findings demonstrate the efficacy of knowledge graphs as model priors, and show early signs that RL can refine LLMs into generalizable tools for predicting complex biological responses.

Modern data-driven applications increasingly involve learning from multiple heterogeneous sources, where a target dataset is limited but related information is available across domains. Naively combining these sources can degrade performance when relevance varies or spurious signals are present, posing a fundamental challenge for trustworthy cross-domain learning. We propose Projection Transfer Learning (ProjectionTL), a unified framework that integrates hierarchical Bayesian modeling with adaptive projection for selective knowledge transfer. The key idea is to decouple transfer at two levels: first, we construct a source-guided hierarchical prior that aggregates information across sources using data-driven weights, capturing global alignment between each source and the target; second, we refine this borrowing through a posterior-projection step that operates at the feature level, selectively retaining coordinates that exhibit local agreement with the target signal. This two-stage design enables the method to simultaneously perform source selection and feature selection, thereby mitigating negative transfer while preserving interpretability. ProjectionTL provides a principled approach to integrating heterogeneous data across domains, bridging statistical modeling and modern machine learning paradigms for robust and interpretable transfer. Through simulations and real-world biomedical applications, we demonstrate improved accuracy, stability, and interpretability compared to existing methods. Our framework offers a scalable and generalizable strategy for trustworthy cross-domain learning in high-dimensional settings.