Medical Ontology

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.

Word-level cross-lingual alignment is central to annotation projection, translation auditing, and cross-lingual faithfulness estimation, yet existing neural aligners are rarely adapted to specialized domains. In this paper, we introduce ClinicalAligner26AM, a large-context multilingual aligner model for biomedical and clinical text initialized from ClinicalEncoder26AM. Our training recipe is inspired by AWESoME Align. We build our soft alignment target by sharpening with Sinkhorn-Knop optimal transport a cost matrix established for parallel clinical texts and conversations through the fusion of sentence-level, phrase-level, and token-level signals. We distill this sharpened alignment matrix directly into our student aligner, by encouraging its naive cosine-based token similarity scores to match this target. At inference time, we project source-span scores through the learned token alignment matrix and decode the longest valid high-scoring span in the target text, optionally supported by MultiClinNER predictions summarized in Appendix B. We evaluate CA26AM on the MultiClinCorpus shared task, which projects Spanish clinical entity annotations into six target languages. Our two submitted systems ranked respectively first and second across all languages and entity types, with character-weighted F1 scores above 0.95 in nearly all settings.

DNA cis-regulatory elements (CREs) such as enhancers control gene expression levels. Accurately predicting regulatory activity from DNA sequences is valuable but challenging, as it requires understanding complex biological regulatory processes. Existing methods typically regress activity scores from sequences in a black-box manner, limiting both interpretability and regression performance. Meanwhile, large language models (LLMs) benefit from explicit reasoning processes, yet directly applying LLMs to raw DNA sequences performs poorly. In this paper, we bridge this gap by introducing R3LM, a framework that teaches LLMs reasoning-informed regression on regulatory DNA through structured biological knowledge. Specifically, we design a biologically grounded data format that structures DNA's regulatory information for improved LLM understanding, and construct CRE-ReasonBench, the first dataset that associates DNA sequences and activity scores with mechanistic reasoning traces. Through two-stage training that first teaches LLMs reasoning over structured biological information then performs regression, R3LM achieves state-of-the-art performance on enhancer prediction across three cell types, outperforming both LLMs with raw sequence input and specialized DNA models while providing interpretable mechanistic explanations. We expect R3LM as an interpretable reward model that can effectively assist biologists in CRE design. Code is available at https://github.com/DuanYi516/R3LM.

Medical knowledge graphs (MKGs) infused with clinical knowledge have been increasingly used to model electronic health records (EHRs) to support interpretable predictions in healthcare domain. However, existing MKG-based approaches are limited in capturing pairwise relations between clinical concepts (e.g., conditions, procedures, and medications), and restricts their ability to model higher-order interactions among co-occurring or semantically related concepts. In addition, most representation learning methods that leverage MKGs either collapse temporal information across visits or lack an explicit mechanism for modeling long-range temporal dependencies, which is critical for clinical tasks such as mortality prediction. To mitigate these limitations, we propose HoT-SSM, a parameter efficient and higher-order temporal graph reasoning with state space models. For each visit, HoT-SSM constructs hypergraphs by grouping semantically related clinical concepts into hyperedges using domain knowledge, thereby preserving visit-level clinical context. Further, to model the temporal dynamics while learning the representations, we introduce a novel dynamic hypergraph-based state space model that explicitly captures patients latent state evolution over time while preserving long-range information. The learned representations are used for downstream clinical prediction and reasoning. Experiments on MIMIC-III and MIMIC-IV datasets shows significant performance improvement over the current state-of-the-art models, demonstrating the effectiveness of jointly modeling higher-order clinical interactions and long-range temporal dependencies.

A central goal of biomedicine is to understand, predict and ultimately control the dynamic mechanisms by which biological systems respond to perturbations, disease progression and therapeutic intervention. Although foundation models and large language models have accelerated biomedical data interpretation, most current systems remain focused on static pattern recognition rather than prospective simulation of biological futures. Here we propose biomedical world models as a paradigm for AI-driven discovery. These models learn latent representations of molecular, cellular, tissue and clinical states, together with intervention-conditioned dynamics that allow future trajectories to be simulated before actions are taken. We discuss how biomedical world models could function as data engines, environment simulators and scientific planning substrates across applications including virtual cells, organoids, virtual patients and surgical simulation. We outline the data infrastructure, evaluation benchmarks, safety constraints and governance frameworks required. Biomedical world models may provide a foundation for simulation-guided, closed-loop and experimentally actionable biomedical discovery.

Systematic reviews rely on forest plots to synthesise quantitative evidence across biomedical studies, but generating them remains a fragmented and labour-intensive process. Researchers must interpret complex clinical texts, manually extract outcome data from trials, define appropriate interventions and comparators, harmonise inconsistent study designs, and carry out meta-analytic computations-typically using specialised software that demands structured inputs and domain expertise. While recent work has demonstrated that large language models can extract study-level data from unstructured text, no existing system automates the complete pipeline from raw documents to synthesised forest plots. To address this gap, we introduce AutoForest, the first end-to-end system that generates publication-ready forest plots directly from biomedical papers. Given one or more study papers, AutoForest automatically suggests ICO (Intervention, Comparator, Outcome) elements, extracts outcome data, performs statistical synthesis, and renders the final forest plot. We describe the system architecture, user interface and demonstrate its effectiveness on real-world examples through a user study involving clinicians, showing how AutoForest can accelerate evidence synthesis and substantially lower the barrier to conducting meta-analyses.

Systematic characterization of drug-disease relationships is essential for drug discovery and repurposing, yet is hindered by the heterogeneity and rapid growth of biomedical literature. Existing datasets rely on labor-intensive curation and are often incomplete, while LLM-only approaches suffer from hallucination and weak evidence grounding. We introduce UniD$^3$, a unified framework that integrates Large Language Models with Knowledge Graph-enhanced Retrieval-Augmented Generation (KG-RAG) to extract, organize, and validate drug-disease knowledge across Drug-Disease Matching (DDM), Drug Effectiveness Assessment (DEA), and Drug-Target Analysis (DTA). UniD$^3$ processes 157,849 PubMed articles with Llama 3.3-70B and constructs knowledge graphs via a dual-stage strategy combining paper-level extraction with KG-level consolidation centered on drug and disease entities. These graphs support KG-RAG-based generation of structured datasets, evaluated through external benchmarks, fuzzy matching with curated resources, and clinician review. UniD$^3$ produces six knowledge graphs and large-scale datasets, including 28,915 DDM, 15,042 DEA, and over 4,000 DTA QA pairs. External validation shows strong performance (F1: 0.85-0.87 for DDM/DEA; 0.82 for DTA), with clinician review confirming high reliability (AUROC = 0.90). KG-RAG-augmented models outperform standalone LLMs, and the UniD$^3$ chatbot enables interpretable, citation-supported exploration of drug-disease relationships. UniD$^3$ provides a scalable, extensible framework for transforming unstructured biomedical literature into high-quality, structured drug-disease knowledge, supporting AI-driven discovery, repurposing, and precision medicine.

General-purpose VLMs remain unreliable for biomedical research because valid answers in scientific papers depend on evidence split across figures, tables, charts, captions, and referring text. Existing post-training pipelines are bottlenecked by costly expert annotation and by synthetic data that drops this evidence structure. We present Ryze, a fully automated system that converts raw biomedical papers into an evidence-enriched training set and a domain-specialized VLM. Ryze synthesizes QA pairs with complete supporting evidence (visual element, caption, extracted structure, and referring paragraphs), reduces layout and OCR errors via chart/table-aware extraction and LLM-based cleansing, and applies a progress-gated post-training strategy combining supervised fine-tuning with reinforcement learning. Starting from Qwen3-VL-8B, Ryze produces BioVLM-8B at under USD 200, achieving 48.0% weighted accuracy on LAB-Bench, outperforming the base model by +12.6 percentage points (pp) and surpassing GPT-5.2 by +3.8 pp. We release Ryze as open source together with the trained BioVLM-8B model.

Biomedical NER is deceptively simple for modern LLMs: plausible biomedical mentions are easy to surface, but corpus-convention correctness depends on annotation conventions, span boundaries, entity granularity, and type schemas. Multi-LLM agreement is a salience signal, not corpus-convention correctness. We introduce a candidate-level panel-output benchmark for panel-surfaced candidate verification, where the unit is an aligned candidate surfaced by an explicitly defined multi-model panel rather than a standalone extractor output. The benchmark aligns eight LLMs' predictions over five public biomedical NER datasets into a candidate master table. BioConCal is an in-domain supervised scorer that instantiates this layer with inference-time gold-free agreement, mention, surface-availability, and document features for a fixed candidate stream. In domain, BioConCal improves AUROC from 0.753 for raw agreement to 0.910. At a validation-selected 0.95 precision target it selects 1,340 candidates at empirical test precision 0.939, compared with 293 for raw agreement. This corresponds to candidate-level recall 0.592 and corpus-level recall 0.523 against a within-panel row-label ceiling of 0.883. The main benefit is not recovering entities missed by every panel member, but reshaping a noisy panel stream into a higher-yield review queue. Under entity-type shift, thresholds require target-domain validation, and exact character localization remains a separate deterministic post-processing step.

We present a protocol to evaluate ChatGPT's ability to generate disease-centric biomedical associations. It outlines how we generate the associations, validate the biological entities using biomedical ontologies, and verify associations using literature. The protocol includes a self-consistency strategy to assess generative reliability across ChatGPT models. To address ontology exact-match limitations, we provide a use case performing semantic verification through a workflow enabled by Retrieval-Augmented Generation (RAG) powered by open-source large language models (LLMs). This enables LLMs to establish truth over content generated by other LLMs and expose hallucination.

Tabular data in knowledge-rich domains often carries a latent prior in the form of Boolean implication relationships (BIRs) between pairs of features. We mine such relationships with a sparse-exception binomial test. The mined implications form a typed directed graph, equivalent to a propositional rule base of 2-literal clauses. We encode this graph as the connectivity of a layered neural network, called BIRDNet, in which each hidden unit corresponds to one mined rule and binds only to its two features. We show two consequences of this design: First, the architecture is sparse by construction: at most $2/d$ of the weights in each BIR layer are active, where $d$ is the input dimension. Second, the model is interpretable: every trained unit keeps a stable symbolic identity, so rules can be read off the network without surrogate models. Unlike most neurosymbolic models, BIRDNet does not consume an external rule base; its structural prior is mined from the data. We evaluate BIRDNet on six transcriptomic and proteomic benchmarks. Our results show that BIRDNet stays within 0.02 AUROC of the strongest dense baseline, at a small accuracy cost, while using up to $96\times$ fewer active parameters than an architecture-matched dense MLP. First-layer rules recover known biological signatures across multiple cancer subtypes and tissue types, including canonical amplicons, lineage-defining co-expression modules, and immune-infiltration markers. Data and code are available at: https://github.com/MAHI-Group/BIRDNet.

ClinicalEncoder26AM is a multilingual Diagnosable ColBERT for clinical and biomedical texts, which aligns at multiple levels its token-level semantic with ClinicalMap25, a clinical latent space inspired by BioLORD-2023 and enriched with synthetic and annotated supervision. The post-training recipe builds upon BGE-M3, and combines synthetic clinical notes, patient--doctor conversations, and annotated resources such as MedMentions, while considering both named-entity-level and sentence-level representations in a multi-adapter distillation, along with a ColBERT-style retrieval objective. In this system demonstration paper, we evaluate the model in the MultiClinNER shared task by finetuning it as a BIO tagger for patient symptoms, disorders, and procedure spans, using a lightweight two-layer CNN head to improve local boundary detection. The resulting system remains simple, processes most documents in a single 8192-token window, and achieves state-of-the-art multilingual entity recall, while achieving Top 5 overall across all entity types and languages in Character-weighted F1 scores. Training curves further show that ClinicalEncoder26AM is markedly more data-efficient than the base M3 model, supporting the usefulness of its clinical post-training for downstream information extraction. The model can be downloaded on https://huggingface.co/Parallia/ClinicalEncoder26AM-Diagnosable-Colbert-L2-for-multilingual-medical-texts

Causal relation extraction (CRE) is central to biomedical text mining, but current resources often conflate causal relations with broader associations, restrict annotation to sentence-level examples, or focus mainly on explicit causal cues. This limits their usefulness for evaluating whether models can recover causal claims as they are actually expressed in biomedical text. We introduce PubMedCausal, a span-level annotated corpus for biomedical CRE built from PubMed abstracts. The corpus contains 30,000 paragraph-level rows, including 3,945 causal rows and 6,491 adjudicated cause--effect pairs. Each causal relation is annotated with full-text cause and effect spans, causality type, and sententiality, enabling evaluation of both causal detection and full-span causal extraction. We benchmark discriminative encoders and open-source generative models across detection and extraction settings. For causal detection, biomedical encoders are strongest, with PubMedBERT reaching an F$_1$ score of 0.7391. For span-level extraction, the best generative baseline is DeepSeek-R1-32B with few-shot prompting, reaching a Cosine Pair F$_1$ of 0.6765. We further test transfer learning by evaluating PubMedCausal-trained encoders on external causal relation datasets, showing that the resource supports cross-dataset evaluation. Our results show that biomedical CRE remains difficult under class imbalance, long causal spans, implicit causality, inter-sentential relations, and prompt sensitivity. Code and Data can be found here: https://github.com/josiahpaul07/PubMedCausal_Exp

Biomedical discovery often requires connecting broad biomedical knowledge with specific experimental or clinical data. Background knowledge suggests relevant mechanisms but is usually too general to map directly onto dataset variables, while data-driven patterns can be dataset-specific and hard to interpret mechanistically. We study this missing link as knowledge contextualization: transforming broad biomedical knowledge into evidence-supported, scenario-grounded propositions that domain experts can inspect, replay, and validate. We propose SCENE, a bi-level multi-agent framework that treats knowledge contextualization as iterative search. The upper level converts broad knowledge into search directions and grounds them in the dataset schema. The lower level executes these directions through multi-objective optimization to identify concrete propositions that balance evidential strength and data support. Feedback between the two levels progressively refines the search. We evaluate SCENE in two settings: discovering patient subgroups with heterogeneous treatment benefits in clinical trial scenarios, and identifying context-specific biological responses in LINCS L1000 studies. In clinical trials, SCENE discovers specific, well-supported subgroups and outperforms existing baselines. In L1000 studies, SCENE identifies perturbational contexts with strong target-response matching and high positive rates. These results show that SCENE bridges broad knowledge and scenario-specific evidence, producing traceable, inspectable hypotheses for follow-up validation.

MedER refers to the identification of medical entities. It is crucial for extracting structured clinical information from unstructured medical text. Many existing systems rely on transformer-based models, which are computationally expensive and difficult to deploy in resource-constrained environments. Furthermore, earlier works often use relaxed evaluation metrics that artificially inflate performance by rewarding correct prediction of dominant "Outside" (O) tokens. In this paper, we propose a lightweight Medical Entity Recognition (MedER) framework for the Bangla language. We establish a rigorous baseline using a 12-layer BanglaBERT model combined with a Conditional Random Field (CRF) layer for exact-boundary entity detection. To address deployment constraints, we compress this teacher model into a 4-layer student network through Knowledge Distillation (KD), where the student learns from the teacher's pre-CRF soft emission logits. Finally, we apply INT8 dynamic quantization to further reduce model size and inference cost. Our final quantized student achieves an 8.6x CPU speedup while requiring nearly 48 percent less storage than the CRF teacher model.

Biological systems are governed by structured molecular interactions, where pathways, regulatory circuits, and functional gene relationships shape cellular behavior and disease progression. Much of this knowledge is naturally represented as graphs. However, most biomedical AI models cannot directly use graph-encoded biological knowledge and instead require compressed low-dimensional representations, which can lose important structure and reduce performance, especially in limited-sample clinical studies. Here, we introduce Graph-in-Graph (GiG), a knowledge graph-modulated deep learning framework for data-efficient clinical prediction. GiG represents each patient as a standalone modular graph, in which curated biological knowledge graphs define edges and patient-specific measurements, such as gene expression, define node features. This design allows multiple biological knowledge graphs to be integrated while preserving gene-gene interactions and pathway topology during patient-level representation learning. Across cohorts comprising nearly 9,700 patients and five clinical tasks, including liquid biopsy cancer detection, prostate cancer diagnosis, and 32-class pan-cancer classification, GiG consistently outperforms traditional and state-of-the-art methods, with the largest gains in limited-sample settings. On the challenging prostate cancer diagnosis task, GiG improves macro-F1 by up to 49 percentage points relative to competing methods. Control experiments replacing real pathway graphs with random topologies confirm that these gains arise from biologically grounded knowledge graph structure rather than graph modeling alone. These findings show that knowledge graph-modulated deep learning can improve robustness, interpretability, and sample efficiency in clinical data analysis, and provide a principled framework for integrating biological knowledge graphs into predictive modeling.

Biomedical knowledge graphs (KGs) treat disease associations as static facts, but temporal information is crucial for clinical reasoning, e.g., a symptom diagnostic of one disease at age 3 may imply a different disease at age 13. Existing KGs such as PrimeKG, Hetionet, and iKraph do not encode when a finding becomes clinically relevant over the course of a disease. This limits their usefulness for longitudinal clinical reasoning and retrieval augmentation. We introduce ChronoMedKG, a temporal biomedical knowledge graph that contains 460,497 evidence-linked triples (filtered from 13M raw extractions) covering 13,431 diseases. Each association is tied to temporal components like onset window or progression stage, which are backed by PMID-traceable evidence and a multi-signal credibility score. The graph is constructed through a disease-autonomous multi-agent pipeline in which multiple frontier LLMs independently extract knowledge from PubMed and PMC literature. Only those relations are kept that are supported by multi-model consensus, survive credibility filtering, as well as ontology alignment. ChronoMedKG scored 92.7% agreement against Orphadata and adds temporal grounding for 6,250 diseases absent from HPOA, Orphadata, and Phenopackets, including 1,657 Orphanet-coded rare diseases. We further introduce ChronoTQA, a benchmark of 3,341 questions across eight task types (six temporal plus two static controls), with a 12-question supplementary probe. Frontier LLMs lose roughly 30 points moving from static to temporal questions; ChronoMedKG retrieval rescues 47-65% of their long-tail failures, against 17-29% for HPOA-RAG. As such, ChronoMedKG provides a crucial temporal axis for retrieval-augmented clinical systems that was previously absent.

Despite recent progress, Biomedical Entity Linking (BEL) with large language models (LLMs) remains computationally inefficient and challenging to deploy in practical settings. In this work, we demonstrate that instruction-tuning of open-source generative models can offer an effective solution when applied at the re-ranking stage of the BEL pipeline. We propose a set-wise instruction-tuning formulation that enables fast and accurate candidate selection. Our method demonstrates strong performance on multiple BEL benchmarks, yielding significant improvements in linking accuracy (3%-24%) while reducing inference time compared to the state-of-the-art. We integrate our generative re-ranker into BeLink, a modular, end-to-end system designed for practical real-world BEL applications.

Materials discovery and biomedical translation increasingly require models that can reason across composition, processing, structure, biological response, manufacturability, safety, and governance constraints. Existing materials and biomedical data ecosystems are powerful but remain poorly coupled for AI-guided discovery. Here we present AIMBio, a conceptual framework for an AI-native, FAIR, and governance-aware decision layer that links materials provenance, biomedical context, knowledge graphs, uncertainty-aware machine learning, and human-in-the-loop active learning. The framework formulates biomedical-materials discovery as constrained multi-objective optimization under uncertainty and introduces practical requirements for metadata, model documentation, risk-tiered governance, evaluation metrics, and phased implementation. To make the roadmap testable, we add a minimum viable prototype specification and a worked pilot for AI-guided nanomaterials for drug delivery. AIMBio is positioned as exploratory and preclinical discovery infrastructure, not as clinical decision-support software; any clinical or regulated-device use would require separate validation, change control, and regulatory review. The central contribution is a publishable platform blueprint for converting fragmented materials and biomedical records into auditable, experimentally actionable, and translationally responsible discovery workflows.

While Large Language Models (LLMs) demonstrate remarkable performance on zero-shot annotation tasks, they often struggle with the specialized conventions of gold-standard benchmarks. We propose the systematic reuse and refinement of annotation guidelines as an alignment mechanism, introducing an iterative moderation framework that simulates the early phases of annotation projects. We evaluate three hypotheses: (1) the efficacy of guideline integration, (2) the advantage of reasoning optimized models, and (3) the viability of moderation under minimal supervision. Testing across biomedical NER tasks (NCBI Disease, BC5CDR, BioRED) with three LLM families (GPT, Gemini, DeepSeek), our results empirically confirm all three hypotheses. While the iterative moderation framework shows good potential in effectively refining guidelines, our analysis also reveals substantial room for improvement.

Biomedical abstracts play a critical role in downstream NLP applications, such as information retrieval, biocuration, and biomedical knowledge discovery. However, a non-trivial number of biomedical articles do not have abstracts, diminishing the utility of these articles for downstream tasks. We propose DPR-BAG (Divide, Prompt, and Refine for Biomedical Abstract Generation), a training-free, zero-shot framework that generates coherent and factually grounded abstracts for biomedical articles with full text but no abstract. DPR-BAG decomposes full-text documents into structured rhetorical facets following the Background-Objective-Methods-Results-Conclusions (BOMRC) schema, performs parallel LLM-based summarization for each facet, and applies a final refinement stage to restore global discourse coherence. On PMC-MAD, a distribution-aligned dataset of 46,309 biomedical articles, DPR-BAG improves abstractive novelty over strong extractive and fine-tuned baselines, while maintaining factual consistency. Our ablation study reveals a counterintuitive finding: increasing prompt complexity or explicitly injecting entity-level guidance can degrade factual alignment, highlighting the importance of controlled prompting strategies. These findings underscore the potential of training-free, structure-aware frameworks for scalable biomedical abstract generation in low-resource settings. Our data and code are available at https://huggingface.co/datasets/pmc-mad/PMC-MAD and https://github.com/ScienceNLP-Lab/MultiTagger-v2/tree/main/DPR-BAG.

Biomedical named entity recognition (NER) and entity linking (EL) strongly depend on annotated corpora, but the utility of these resources for benchmarking is often assumed rather than characterized. We present a corpus-centric framework for diagnosing benchmark-relevant properties directly from corpus annotations, concept links, train-test splits, document metadata, and terminology mappings. The framework organizes standardized statistics into five families: (1) scale, density and label distribution, (2) lexical and conceptual structure, (3) train-test overlap, (4) metadata composition, and (5) terminology coverage where applicable. Applying the framework to nine corpora spanning diseases, chemicals, and cell types, we find that corpus properties can differ substantially, even when they address the same apparent task. We find differences in the evaluation signal they provide, the generalization demands they impose, the degree of train-test reuse they permit, and the regions of biomedical literature and concept space they represent. These differences suggest that commonly reported corpus statistics can be insufficient to characterize what biomedical NER and EL benchmarks evaluate. We argue that corpus-centric diagnostics provide a practical framework for analyzing corpora beyond surface descriptors such as corpus size and entity type, for identifying potential transfer risks, and for interpreting the scope of benchmarking conclusions. We release the framework as open-source code with an interactive dashboard to support reproducing our analyses and characterizing additional corpora.

Biomedical Vision--Language Models (VLMs) have shown remarkable promise in few-shot medical diagnosis but face a critical bottleneck: \textit{fragility to prompt variations}.Existing adaptation frameworks typically optimize visual and textual prompts as independent streams, relying on ideal ``Golden Prompts''. In clinical reality, where descriptions are often noisy and heterogeneous, this modality isolation leads to unstable cross-modal alignment. To address this, we propose BiomedAP, a vision-informed dual-anchor framework with gated cross-modal fusion.BiomedAP enforces synergistic alignment through two mechanisms: (1) Gated Cross-Modal Fusion, which enables layer-wise interaction between modalities, acting as a dynamic noise regulator to suppress irrelevant textual cues; and (2) a Dual-Anchor Constraint that regularizes learnable prompts toward stable semantic centroids derived from both expert templates (High Anchors) and few-shot visual prototypes (Low Anchors). Extensive experiments across 11 benchmarks demonstrate that BiomedAP consistently surpasses baselines, achieving competitive few-shot accuracy and markedly enhanced robustness under prompt perturbations. Our code is available at: https://github.com/tongdiedie/BiomedAP. Keywords: Vision-Language Models; Prompt Learning; Parameter-Efficient Fine-Tuning; Few-shot Learning

Large language models (LLMs) are increasingly used in the mental health domain, yet it remains unclear how well they capture related biomedical knowledge and how reliably they apply it to clinically salient structured judgments. Here, we present a knowledge-graph (KG)-grounded benchmark for assessing LLMs on mental-health entity recognition, relation judgment, and two-hop reasoning. The benchmark is derived from PrimeKG and comprises nine task families with KG-supported answers and controlled negative options. Experiments across 15 closed- and open-source LLMs reveal a persistent recognition-to-judgment gap: leading models achieve near-ceiling performance on entity typing and on the small relation-typing subset, yet they still struggle with relation prediction and two-hop reasoning. Additionally, short KG-derived snippets benefit some models but degrade performance for others. Moreover, output-format reliability can substantially influence measured performance under constrained multiple-choice settings, highlighting the critical role of response validity in benchmark-based evaluation. MHGraphBench should therefore be interpreted as evaluating agreement with a curated mental-health slice of PrimeKG under a constrained multiple-choice interface, rather than as a direct assessment of real-world clinical safety.

Analyzing microscopy images to extract biological object properties (e.g., their morphological organization, temporal dynamics, and population density) is fundamental to various biomedical research. Yet conducting this manually is costly and time-consuming. Though deep learning-based approaches have been explored to automate this process, the substantial diversity of microscopy analysis settings in practice (including variations of biological object types, sample processing protocols, imaging equipment, and analysis tasks, etc.) often renders them ineffective. As a result, these approaches typically require extensive adaptation for different settings, which, however, can impose burdens that are often practically unsustainable for laboratories, forcing biomedical researchers to still commonly rely on manual analysis, thereby severely bottlenecking the pace of biomedical research progress. This situation has created a pressing and long-standing need for a reliable and broadly applicable microscopy image analysis tool, yet such a tool is still missing. To address this gap, we present the first ready-to-use microscopy image analysis framework, MicroscopyMatching, that can reliably perform key analysis tasks (including segmentation, tracking, and counting) across diverse microscopy analysis settings. From a fundamentally different perspective, MicroscopyMatching reformulates diverse microscopy image analysis tasks as a unified matching problem, effectively handling this problem by exploiting the robust matching capability from pre-trained latent diffusion models.

Biomedical retrieval-augmented large language models (LLMs) often face evidence that is incomplete, misleading, or internally contradictory, yet evaluation usually emphasizes answer accuracy under helpful context rather than reliability under conflict. Using HealthContradict, we evaluate six open-weight LLMs under five controlled evidence conditions: no retrieved context, correct-only context, incorrect-only context, and two mixed conditions containing both correct and contradictory documents in opposite orders. In this conflicting-evidence order contrast, where the same two documents are both present and only their order is reversed, accuracy drops for every model and 11.4%--25.2% of predictions flip. To support abstention in these difficult cases, we also evaluate a conflict-aware abstention score that combines model confidence with a detector of evidence conflict. In the two hardest conditions, this score improves selective accuracy over confidence-only, with mean gains of 7.2--33.4 points in incorrect-only (IC') and 3.6--14.4 points in incorrect-first conflicting (ICC') conditions across 75%, 50%, and 25% coverage. These results show that conflicting biomedical evidence is both an uncertainty and robustness problem and motivate evaluation and abstention methods that explicitly account for evidence disagreement.

Biomedical entity linking maps textual mentions to concepts in structured knowledge bases such as UMLS or SNOMED CT. Most existing systems link each mention independently, using only the mention or its surrounding sentence. This ignores dependencies between mentions in the same document and can lead to inconsistent predictions, especially when the same concept appears under different surface forms. We introduce LongBEL, a document-level generative framework that combines full-document context with a memory of previous predictions. To make this memory robust, LongBEL is trained with cross-validated predictions rather than gold labels, reducing the mismatch between training and inference and limiting cascading errors. Experiments on five biomedical benchmarks across English, French, and Spanish show that LongBEL improves over sentence-level generative baselines, with the largest gains on datasets where concepts frequently recur within documents. An ensemble of local, global, and memory-based variants achieves the best results across all benchmarks. Further analysis shows that the largest gains occur on recurring concepts, suggesting that LongBEL mainly improves document-level consistency rather than isolated mention disambiguation.

When adapting an encoder to a new domain, the standard approach is to continue training with Masked Language Modeling (MLM). We show that temporarily switching to Causal Language Modeling (CLM) followed by a short MLM decay improves downstream performance. On biomedical texts with ModernBERT, this CLM detour outperforms MLM baselines trained on identical data and compute across 8 French and 11 English biomedical tasks, by +1.2-2.8pp and +0.3-0.8pp respectively, depending on model size. We investigate the reasons for these gains. We find that CLM's dense supervision impacts low transformer layers (0-7) far more than MLM does. Freezing low layers during CLM eliminates the downstream benefit; freezing mid layers preserves it. The representational changes persist through the MLM decay phase, even when it matches the CLM phase in length, and they scale with model capacity. We release ModernCamemBERT-bio and ModernBERT-bio as state-of-the-art biomedical encoders in Base and Large sizes.

Evaluating large language models (LLMs) in the biomedical domain requires benchmarks that can distinguish reasoning from pattern matching and remain discriminative as model capabilities improve. Existing biomedical question answering (QA) benchmarks are limited in this respect. Multiple-choice formats can allow models to succeed through answer elimination rather than inference, while widely circulated exam-style datasets are increasingly vulnerable to performance saturation and training data contamination. Multi-hop reasoning, defined as the ability to integrate information across multiple sources to derive an answer, is central to clinically meaningful tasks such as diagnostic support, literature-based discovery, and hypothesis generation, yet remains underrepresented in current biomedical QA benchmarks. MedHopQA is a disease-centered multi-hop reasoning benchmark consisting of 1,000 expert-curated question-answer pairs introduced as a shared task at BioCreative IX. Each question requires synthesis of information across two distinct Wikipedia articles, and answers are provided in an open-ended free-text format. Gold annotations are augmented with ontology-grounded synonym sets from MONDO, NCBI Gene, and NCBI Taxonomy to support both lexical and concept-level evaluation. MedHopQA was constructed through a structured process combining human annotation, triage, iterative verification, and LLM-as-a-judge validation. To reduce leaderboard gaming and contamination risk, the 1,000 scored questions are embedded within a publicly downloadable set of 10,000 questions, with answers withheld, on a CodaBench leaderboard. MedHopQA provides both a benchmark and a reusable framework for constructing future biomedical QA datasets that prioritize compositional reasoning, saturation resistance, and contamination resistance as core design constraints.

Accurately and consistently indexing biomedical literature by publication type and study design is essential for supporting evidence synthesis and knowledge discovery. Prior work on automated publication type and study design indexing has primarily focused on expanding label coverage, enriching feature representations, and improving in-domain accuracy, with evaluation typically conducted on data drawn from the same distribution as training. Although pretrained biomedical language models achieve strong performance under these settings, models optimized for in-domain accuracy may rely on superficial lexical or dataset-specific cues, resulting in reduced robustness under distributional shift. In this study, we introduce an evaluation framework based on controlled semantic perturbations to assess the robustness of a publication type classifier and investigate robustness-oriented training strategies that combine entity masking and domain-adversarial training to mitigate reliance on spurious topical correlations. Our results show that the commonly observed trade-off between robustness and in-domain accuracy can be mitigated when robustness objectives are designed to selectively suppress non-task-defining features while preserving salient methodological signals. We find that these improvements arise from two complementary mechanisms: (1) increased reliance on explicit methodological cues when such cues are present in the input, and (2) reduced reliance on spurious domain-specific topical features. These findings highlight the importance of feature-level robustness analysis for publication type and study design classification and suggest that refining masking and adversarial objectives to more selectively suppress topical information may further improve robustness. Data, code, and models are available at: https://github.com/ScienceNLP-Lab/MultiTagger-v2/tree/main/ICHI

Biomedical knowledge graphs underwrite drug repurposing and clinical decision support, yet the upstream ontologies they depend on update on independent cycles that add millions of edges and deprecate hundreds of thousands more between releases. Yet existing continual graph learning has been studied almost exclusively on synthetic random splits of static, generic KGs, a regime that cannot reproduce the asynchronous, structured evolution real biomedical KGs undergo. To this end, we introduce PrimeKG-CL, a CGL benchmark built from nine authoritative biomedical databases (129K+ nodes, 8.1M+ edges, 10 node types, 30 relation types) with two genuine temporal snapshots (June 2021, July 2023; 5.83M edges added, 889K removed, 7.21M persistent), 10 entity-type-grouped tasks, multimodal node features, and a per-task persistent/added/removed test stratification. On three tasks (biomedical relationship prediction, entity classification, KGQA), we evaluate six CL strategies across four KGE decoders, plus LKGE, an LLM-RAG agent, and CMKL. We find that decoder choice and continual learning strategy interact strongly: no single strategy performs best across all decoders, and mismatched combinations can significantly degrade performance. Moreover, only DistMult exhibits a clear separation between persistent and deprecated knowledge, indicating that standard metrics conflate retention of still-valid facts with failure to forget outdated ones; this effect is absent under RotatE. In addition, multimodal features improve entity-level tasks by up to 60%, and a recent CKGE framework (IncDE) failed to scale to our 5.67M-triple base task across five attempts up to 350GB RAM. Data, pipeline, baselines, and the stratified split are released openly. Dataset:huggingface.co/datasets/yradwan147/PrimeKGCL|Code:github.com/yradwan147/primekg-cl-neurips2026

Biomedical knowledge graphs are increasingly large, dynamic, and multimodal, driven by rapid advances in biotechnology such as high-throughput sequencing. Machine learning models can infer previously unobserved biomedical relationships and characterize biomedical entities in these graphs, but existing knowledge graph embedding methods and their continual learning extensions either assume static graph structure or fail to exploit multimodal information under evolving data distributions. They also apply uniform regularization across all model parameters, ignoring that different modalities may exhibit distinct forgetting dynamics as the graph evolves. We propose the Continual Multimodal Knowledge Graph Learner (CMKL), a CL framework for biomedical KGs that natively encodes structure, text, and molecules, fuses them through a Mixture-of-Experts (MoE) router, and protects previously learned knowledge with standard EWC regularization and a K-means-diverse multimodal replay buffer. We evaluate CMKL on a 129K-entity biomedical continual benchmark with 10 tasks. On continual biomedical entity classification, CMKL reaches AP 0.591 versus 0.370 for the strongest structural baseline, a 60% gain that is driven by access to multimodal features and preserved across the sequence with near-zero forgetting (AF 0.008). On continual relationship prediction, CMKL reaches AP $0.062$, matching Naive Sequential and EWC (0.058) within seed noise and outperforming Joint Training (0.047, p=0.045) and LKGE (0.039). A frozen-text ablation reaches AP 0.136, more than double any jointly trained model, yet that signal is unreachable by margin-ranking gradients: the greedy-modality asymmetry lives at the representation level, not the fusion level, and MoE routing manages it by suppressing the unreachable modality without forcing it through a learned bottleneck. Code: github.com/yradwan147/cmkl-neurips2026

Cell-type-specific marker genes are fundamental to plant biology, yet existing resources primarily rely on curated databases or high-throughput studies without explicitly modeling the supporting evidence found in scientific literature. We introduce PlantMarkerBench, a multi-species benchmark for evaluating literature-grounded plant marker evidence interpretation from full-text biological papers. PlantMarkerBench is constructed using a modular curation pipeline integrating large-scale literature retrieval, hybrid search, species-aware biological grounding, structured evidence extraction, and targeted human review. The benchmark spans four plant species -- Arabidopsis, maize, rice, and tomato -- and contains 5,550 sentence-level evidence instances annotated for marker-evidence validity, evidence type, and support strength. We define two benchmark tasks: determining whether a candidate sentence provides valid marker evidence for a gene-cell-type pair, and classifying the evidence into expression, localization, function, indirect, or negative categories. We benchmark diverse open-weight and closed-source language models across species and prompting strategies. Although frontier models achieve relatively strong performance on direct expression evidence, performance drops substantially on functional, indirect, and weak-support evidence, with evidence-type confusion emerging as a dominant failure mode. Open-weight models additionally exhibit elevated false-positive rates under ambiguous biological contexts. PlantMarkerBench provides a challenging and reproducible evaluation framework for literature-grounded biological evidence attribution and supports future research on trustworthy scientific information extraction and AI-assisted plant biology.

Graph neural networks (GNNs) are increasingly used to model biological systems, yet the reliability of post-hoc explanation methods for recovering meaningful molecular mechanisms remains unclear. Here, we systematically evaluate four widely used approaches: Saliency Attribution (SA), Integrated Gradients (IG), GNNExplainer, and Layer-wise Relevance Propagation (LRP) for identifying disease-relevant structure in breast cancer RNA-seq data projected onto a protein-protein interaction network. Using synthetic benchmarks with known ground-truth motifs, we show that explanation methods recover distinct signal organizations: SA performs best for sparse single-node drivers, whereas IG and LRP preferentially recover distributed pathway-like and cascade-like signals. In TCGA BRCA data, we identify a consistent topological signature of disease-associated hubs in which attribution peaks in the immediate 1-hop neighborhood and decays across successive network shells, a pattern most pronounced for IG and LRP and associated with strong enrichment of known cancer hubs. We further observe a trade-off between local hub enrichment and global gene ranking performance, with IG optimizing local enrichment and SA achieving superior global discrimination. Motivated by these complementary behaviors, we introduce a framework combining a shell-based hub score with consensus ranking across explainers. Consensus scores improve prioritization of canonical cancer genes (TP53, BRCA1, ESR1, MYC), reduce dependence on node degree, and, especially when tuned, outperform individual methods. Pathway enrichment further reveals improved recovery of biologically coherent cancer programs, including ERBB2, RTK, MAPK, immune, and cytokine signaling. Together, these results demonstrate that topology-aware integration of graph explanations can improve biological interpretability and biologically relevant molecular recovery.

Manually curated biomedical repositories -- spanning bioactivity, genomics, and chemistry -- are expensive to maintain, lag behind primary literature, and discard experimental context, obscuring nuances needed to assess data correctness and coverage. We show that PubMed itself can be autonomously and cost-effectively turned into structured datasets that are larger, more nuanced, and more accurate than the curated databases they replace. We present three coupled contributions: (1) an LLM-based entity-tagging pipeline, grounded in nine biomedical ontologies, that tags 4.5B entities across 19 categories in a 22.5M-paper, 2.5T-token PubMed corpus; (2) hybrid sparse-dense retrieval supporting entity-filtered semantic queries over the tagged corpus; and (3) Starling, a multi-agent deep research system that, given only a natural-language task description, designs precision- and recall-targeted retrieval filters, induces an extraction schema, and emits structured records with nuance-rich fields and supporting passages. Across six tasks -- blood-brain barrier permeability, oral bioavailability, acute toxicity (LD50), gene-disease associations, protein subcellular localization, and chemical reactions -- Starling produces ~6.3M records (91K-3M per task); several are, to our knowledge, the largest public datasets for their property. Frontier-model rejection of our extractions is 0.6-7.7% across tasks, far below error rates we measure on widely used curated counterparts (e.g., 16.5% on BBB_Martins, 7.3% on Bioavailability_Ma). Beyond scale and accuracy, the supporting passages carry nuance tabular databases discard -- e.g., oral bioavailability may depend on fed vs. fasted state. Together, the corpus, retrieval, and agent establish a foundation for AI-driven therapeutic design. Code and datasets: https://github.com/starling-labs/starling.

Zero-shot single-cell cell-type annotation aims to determine a cell's type from a given set of expressed genes without any training. Existing knowledge-graph-based RAG approaches retrieve evidence by expanding from source entities and relying on iterative LLM reasoning. However, in this setting each query contains tens to hundreds of genes, where no single gene is decisive and the label emerges only from their collective co-occurrence. Such hyper-entity queries fundamentally challenge local, entity-wise exploration strategies, which reason from individual genes, leading to poor scalability and substantial LLM cost. We propose GATHER (Graph-Aware Traversal with Hyper-Entity Retrieval), a convergence-centric retriever tailored to hyper-entity queries. It performs global multi-source graph traversal and identifies topological convergence points -- nodes jointly reachable from many input genes. These convergence nodes act as high-information hyper-entities that capture entity synergy. By incorporating node- and path-importance scoring, GATHER selects informative evidence entirely without LLM involvement during retrieval. Instantiated on a self-constructed cell-centric biological knowledge graph (VCKG), GATHER outperforms strong KG-RAG baselines (ToG, ToG-2, RoG, PoG) on two datasets (Immune and Lung), achieving the highest exact-match accuracy (27.45% and 59.64%) with only a single LLM call per sample, compared to 2--61 calls for KG-RAG baselines. Our results demonstrate that convergence nodes compress multi-entity signals into compact, high-information evidence that conveys more per item than multi-hop paths, providing an efficient global alternative to local entity-wise reasoning.

Reproducing and comparing deep research agents today is hard: the same backbone evaluated on the same benchmark can report different accuracies across papers because the harness and tool registry differ, and integrating a new model into a comparable evaluation surface costs weeks of model-specific engineering. These are symptoms of a broader reproducibility problem in deep research agent research. Here, we introduce BioMedArena, an open-source toolkit that addresses this reproducibility gap and provides an arena for comparing deep research agents under a shared evaluation environment. BioMedArena decouples six layers of biomedical agent evaluation -- benchmark loading, tool exposure, tool selection, harness mode, context management, and scoring -- and exposes 166 biomedical benchmarks and 75 biomedical tools across 9 functional families. Adding a new model, benchmark, or tool can be accomplished with a few-line provider adapter. Beyond evaluation infrastructure, BioMedArena ships a library of high-quality reference components: 6 agent harnesses (including our proposed Mutual-Evolve) and 6 context-management strategies, any of which can be equipped on any backbone. Equipping these components substantially improves all 12 backbones; on each of 8 representative biomedical benchmarks, the best equipped backbone surpasses prior state-of-the-art (SOTA), by 15.01 percentage points on average. The toolkit, configurations, and per-task traces are available at https://github.com/AI-in-Health/BioMedArena.

Translational medicine turns underspecified development goals into evidence synthesis that must combine literature, trials, patents, and quantitative multi-omics analysis while preserving identifiers, uncertainty, and retrievable provenance. General-purpose foundation models and off-the-shelf tool-augmented or multi-agent systems are not built for this: they tend to produce single-shot answers or run open-endedly, and fall short on the auditable, scenario-specific workflows that heterogeneous biomedical sources demand. This paper introduces Ingenix BioResearcher, a scenario-guided multi-agent system that maps queries to versioned research playbooks, delegates to specialized subagents over 30+ tools and machine-learning endpoints, mixes structured database access with sandboxed code for genome-scale analyses, and applies claim-level multi-model reconciliation before editorial assembly. We evaluate BioResearcher across unit-level capabilities, open-ended biomedical reasoning, and end-to-end clinical discovery. It leads evaluated baselines on 109 single-step tests (83.49% pass rate; 0.892 average score), achieves strong biomedical benchmark performance (89.33% on BixBench-Verified-50 and the top 0.758 mean score on BaisBench Scientific Discovery), and leads on a 30-query clinical end-to-end benchmark with the highest positive hit rate (74.7% $\pm$ 3.3%) and negative clear rate (96.8% $\pm$ 0.2%). These results show broad, competitive performance across unit-level, open-ended, and end-to-end clinical evaluations.

Despite the success of large language models (LLMs) on general-purpose tasks, their performance in highly specialized domains such as biomedicine remains unsatisfactory. A key limitation is the inability of LLMs to effectively leverage biomedical tools, which clinical experts and biomedical researchers rely on extensively in daily workflows. While recent general-domain tool-calling datasets have substantially improved the capabilities of LLM agents, existing efforts in the biomedical domain largely rely on in-context learning and restrict models to a small set of tools. To address this gap, we introduce BioTool, a comprehensive biomedical tool-calling dataset designed for fine-tuning LLMs. BioTool comprises 34 frequently used tools collected from the NCBI, Ensembl, and UniProt databases, along with 7,040 high-quality, human-verified query-API call pairs spanning variation, genomics, proteomics, evolution, and general biology. Fine-tuning a 4-billion-parameter LLM on BioTool yields substantial improvements in biomedical tool-calling performance, outperforming cutting-edge commercial LLMs such as GPT-5.1. Furthermore, human expert evaluations demonstrate that integrating a BioTool-fine-tuned tool caller significantly improves downstream answer quality compared to the same LLM without tool usage, highlighting the effectiveness of BioTool in enhancing the biomedical capabilities of LLMs. The full dataset and evaluation code are available at https://github.com/gxx27/BioTool

This study presents a systematic approach to identifying and characterizing student misconceptions in online learning environments through a novel combination of quantitative performance analysis and large language model (LLM) assessment. We analyzed data from 9 course periods across 5 online biomedical science courses, encompassing 3,802 medical student enrollments. Using data from 40-50 topic-focused quizzes per course, we developed a two-stage methodology. First, we identified challenging central topics using quiz-level performance metrics. Second, we employed LLMs to characterize the underlying misconceptions in these high-priority areas. By examining student performance on first attempts across primarily multiple-choice questions (MCQs), we identified consistently challenging topics that were also central to course objectives. We then leveraged recent advances in generative AI to analyze three distinct data sources in combination: quiz question content, student response patterns, and lecture transcripts. This approach revealed actionable insights about student misconceptions that were not apparent from performance data alone. The quality of the LLM-identified misconceptions was rated as excellent by subject matter experts. We also conducted teacher interviews to assess the perceived utility of our topic identification method. Faculty found that data-driven identification of challenging topics was valuable and corroborated their own classroom observations. This methodology provides a scalable approach to characterizing student difficulties in learning environments where quizzes are used. Our findings demonstrate the potential for targeted and potentially personalized interventions in future course iterations, with clear pathways for measuring intervention effectiveness through follow-up quiz performance.

Biomedical knowledge graphs (KGs) are widely used in the life sciences, yet many are derived from unstructured documents and therefore lack schema-level constraints, whereas graphs assembled from structured resources are difficult to harmonize into a unified representation. We present OptimusKG, a multimodal biomedical labeled property graph (LPG) built from structured and semi-structured resources to preserve factual, type-specific metadata across molecular, anatomical, clinical, and environmental domains. OptimusKG contains 190,939 nodes across 10 entity types, 21,818,752 edges across 27 edge types, and 67,070,490 property instances encoding 109,665,797 values across 145 distinct property keys, derived from 18 ontologies and controlled vocabularies. The graph enforces a top-level schema for nodes and edges and retains granular, type-specific properties, cross-references, and provenance. We assessed the validity of OptimusKG by evaluating whether graph relationships are supported by evidence from the scientific literature using a multimodal agent, PaperQA3. PaperQA3 identified supporting evidence for 70.0% of sampled edges, whereas 83.4% of sampled false edges received no supporting evidence. Edges without literature support were concentrated in associations derived from experimental and functional genomics resources, suggesting that OptimusKG captures biomedical knowledge that may precede synthesis in the scientific literature. OptimusKG is distributed as Apache Parquet files, providing a standardized resource for graph-based machine learning, knowledge-grounded retrieval with large language models, and biomedical discovery use cases such as hypothesis generation.

This paper presents a principled and scalable framework for systematically generating complex Question Answering (QA) data. In the core of this framework is a graphlet-anchored generation process, where small subgraphs from a Knowledge Graph (KG) are used in a structured prompt to control the complexity and ensure the factual grounding of questions generated by Large Language Models. The first instantiation of this framework is BioGraphletQA, a new biomedical KGQA dataset of 119,856 QA pairs. Each entry is grounded in a graphlet of up to five nodes from the OREGANO KG, with most of the pairs being enriched with relevant document snippets from PubMed. We start by demonstrating the framework's value and the dataset's quality through evaluation by a domain expert on 106 QA pairs, confirming the high scientific validity and complexity of the generated data. Secondly, we establish its practical utility by showing that augmenting downstream benchmarks with our data improves accuracy on PubMedQA from 49.2% to 68.5% in a low-resource setting, and on MedQA from a 41.4% baseline to 44.8% in a full-resource setting. Our framework provides a robust and generalizable solution for creating critical resources to advance complex QA tasks, including MCQA and KGQA. All resources supporting this work, including the dataset (https://zenodo.org/records/17381119) and framework code (https://github.com/ieeta-pt/BioGraphletQA), are publicly available to facilitate use, reproducibility and extension.

Multimodal Large Language Models (MLLMs) have shown transformative potential in medical applications, yet their performance is hindered by conventional data curation strategies that rely on coarse-grained partitioning by modality or department. Such fragmented approaches fail to capture the hierarchical and interconnected nature of clinical medical knowledge, limiting the models' ability to perform fine-grained recognition and complex reasoning. In this paper, we propose a novel Entity-Centric Medical Data Engineering framework. We automatically extract entities from authoritative medical literature to construct a Medical Entity Tree (MET), a hierarchical structure that systematically encodes diseases, anatomical structures, modalities, and symptoms into a unified knowledge repository. Building upon the MET, we propose an advanced data engine that includes: (1) node-guided retrieval to anchor raw data to specific medical concepts, (2) a two-stage hybrid filtering and alignment pipeline to ensure precise visual-semantic correspondence, and (3) knowledge-aware data synthesis to generate enriched captions and targeted reasoning VQA pairs, leveraging structural constraints. Extensive evaluations across six medical benchmarks demonstrate that our approach significantly enhances the medical capabilities of general-purpose MLLMs, improving their ability to handle complex clinical queries and achieve state-of-the-art performance in diverse medical contexts.

Liver cirrhosis is a major global health problem causing millions of deaths annually, and timely detection with aggressive treatment can significantly improve patients' quality of life. Modelling complex diseases from biomedical data is computationally challenging due to high dimensionality, strong feature correlations, noise, and limited labelled samples. Conventional Machine Learning (ML) pipelines often struggle with robustness, interpretability, and generalisation under such conditions. In this study, we propose an ML-driven multi-stage decision framework for complex disease modelling and therapeutic exploration. The framework integrates single-cell transcriptomic profiling, high-dimensional network-based feature stabilisation, multi-model learning, deep representation construction, and post-hoc decision support. Specifically, single-cell sequencing data were analysed to identify key cellular subpopulations, followed by high-dimensional weighted gene co-expression network analysis (hdWGCNA) to stabilise gene modules under sparsity and noise. To enhance non-linear feature interaction modelling, tabular molecular features were restructured into two-dimensional disease maps and analysed using a CNN. Finally, molecular docking was incorporated as a decision-support module to evaluate candidate therapeutic compounds. Using liver cirrhosis as a representative case, the framework identified a disease-associated endothelial subpopulation and extracted seven robust signature genes (HSPB1, GADD45A, CLDN5, ATP1B3, C1QBP, ENPP2, and PARL). The CNN-based representation learning module outperformed conventional pipelines in classification. The framework is disease-agnostic and readily extends to other omics-driven biomedical applications involving uncertainty, heterogeneity, and limited samples.

Biomedical findings often seem to conflict across studies, but many of these differences are context-dependent rather than true contradictions. Variations in cohort, geography, assay protocol, disease subtype, and clinical setting can make both claims locally valid. Existing NLI and scientific claim-verification benchmarks reduce such cases to entailment, contradiction, or neutral, failing to capture the contextual structure behind divergence. To address this, we introduce BioDivergence, an evaluation framework with a six-class conflict taxonomy, a 13-axis divergence ontology, and four structured outputs per claim pair: conflict type, divergence axes, dominant confounder, and reconciliation explanation. We release BioDivergence-Silver-v1.0, an article-disjoint silver benchmark of 11,865 claim pairs across five biomedical domains, alongside a legacy deduplicated variant for comparison. Results show notable ranking differences between the two variants, with the fine-tuned reference model dropping about 12 points under the article-disjoint setting, while Mistral-7B-Instruct-v0.3 achieves 0.5523 accuracy and 0.3894 contextual-F1 on the 842-example primary test set. BioDivergence offers a more faithful way to distinguish contextual divergence from direct contradiction and to separate article-level memorization from genuine task learning.

Reliable biomedical and clinical retrieval requires more than strong ranking performance: it requires a practical way to find systematic model failures and curate the training evidence needed to correct them. Late-interaction models such as ColBERT provide a first solution thanks to the interpretable token-level interaction scores they expose between document and query tokens. Yet this interpretability is shallow: it explains a particular document--query pairwise score, but does not reveal whether the model has learned a clinical concept in a stable, reusable, and context-sensitive way across diverse expressions. As a result, these scores provide limited support for diagnosing misunderstandings, identifying irreasonably distant biomedical concepts, or deciding what additional data or feedback is needed to address this. In this short position paper, we propose Diagnosable ColBERT, a framework that aligns ColBERT token embeddings to a reference latent space grounded in clinical knowledge and expert-provided conceptual similarity constraints. This alignment turns document encodings into inspectable evidence of what the model appears to understand, enabling more direct error diagnosis and more principled data curation without relying on large batteries of diagnostic queries.

Extracting clinically relevant information from unstructured medical narratives such as admission notes, discharge summaries, and emergency case histories remains a challenge in clinical natural language processing (NLP). Medical Entity Recognition (MER) identifies meaningful concepts embedded in these records. Recent advancements in large language models (LLMs) have shown competitive MER performance; however, evaluations often focus on general entity types, offering limited utility for real-world clinical needs requiring finer-grained extraction. To address this gap, we rigorously evaluated the open-source LLaMA3 model for fine-grained medical entity recognition across 18 clinically detailed categories. To optimize performance, we employed three learning paradigms: zero-shot, few-shot, and fine-tuning with Low-Rank Adaptation (LoRA). To further enhance few-shot learning, we introduced two example selection methods based on token- and sentence-level embedding similarity, utilizing a pre-trained BioBERT model. Unlike prior work assessing zero-shot and few-shot performance on proprietary models (e.g., GPT-4) or fine-tuning different architectures, we ensured methodological consistency by applying all strategies to a unified LLaMA3 backbone, enabling fair comparison across learning settings. Our results showed that fine-tuned LLaMA3 surpasses zero-shot and few-shot approaches by 63.11% and 35.63%, respectivel respectively, achieving an F1 score of 81.24% in granular medical entity extraction.

Drug repurposing is often framed as a candidate identification task, but existing approaches provide limited guidance for distinguishing biologically plausible candidates from historically well-connected ones. Here we introduce DrugKLM, a hybrid framework that integrates biomedical knowledge graph structure with large language model-based mechanistic reasoning to enable mechanistically grounded therapeutic prioritization. Across benchmark datasets, DrugKLM outperforms knowledge graph-only and language model-only baselines, including TxGNN. Beyond improved recall, DrugKLM confidence scores exhibit functional alignment with molecular phenotypes: higher scores are associated with transcriptional signatures linked to improved survival across 12 TCGA cancers. The scoring framework preferentially captures biologically perturbational signals rather than historical indication patterns. Expert curation across five cancers further reveals systematic differences in prioritization behavior, with DrugKLM elevating candidates supported by coherent mechanistic rationale and disease-specific clinical context. Together, these results establish DrugKLM as an evidence-integrative framework that translates heterogeneous biomedical data into mechanistically interpretable and clinically grounded therapeutic hypotheses.

Effective biomedical information retrieval requires modeling domain semantics and hierarchical relationships among biomedical texts. Existing biomedical generative retrievers build on coarse binary relevance signals, limiting their ability to capture semantic overlap. We propose BioHiCL (Biomedical Retrieval with Hierarchical Multi-Label Contrastive Learning), which leverages hierarchical MeSH annotations to provide structured supervision for multi-label contrastive learning. Our models, BioHiCL-Base (0.1B) and BioHiCL-Large (0.3B), achieve promising performance on biomedical retrieval, sentence similarity, and question answering tasks, while remaining computationally efficient for deployment.

The integration of Large Language Models (LLMs) into scientific workflows presents exciting opportunities to accelerate biomedical discovery. However, the reactive nature of LLMs, which respond only when prompted, limits their effectiveness in collaborative settings that demand foresight and autonomous engagement. In this study, we introduce CoLabScience, a proactive LLM assistant designed to enhance biomedical collaboration between AI systems and human experts through timely, context-aware interventions. At the core of our method is PULI (Positive-Unlabeled Learning-to-Intervene), a novel framework trained with a reinforcement learning objective to determine when and how to intervene in streaming scientific discussions, by leveraging the team's project proposal and long- and short-term conversational memory. To support this work, we introduce BSDD (Biomedical Streaming Dialogue Dataset), a new benchmark of simulated research discussion dialogues with intervention points derived from PubMed articles. Experimental results show that PULI significantly outperforms existing baselines in both intervention precision and collaborative task utility, highlighting the potential of proactive LLMs as intelligent scientific assistants.

Cross-lingual biomedical entity linking (BEL) maps mentions in any language to unique identifiers in a biomedical knowledge base, supporting clinical and biomedical NLP applications. We identify two issues affecting current systems. First, the UMLS (Bodenreider,2004) aliases used to train cross-lingual BEL retrievers are heavily skewed toward English, so retrievers generalize poorly to non-English mentions. Second, although context is often necessary for disambiguation, naively injecting context into retrievers trained only to align aliases severely degrades retrieval. We propose BioELX, a retrieve-rerank framework that addresses both issues. For retrieval, we continue training SapBERT_multi (Liu et al., 2021b) using Wikidata-derived cross-lingual alias supervision, forming shared concept neighborhoods across languages. For reranking, we adapt pretrained LLM rerankers to entity linking through mention-anchored prompting, which marks the target mention so that rerankers score candidates with respect to the intended mention rather than other salient tokens in the context. Experiments show that BioELX achieves new state-of-the-art results on four cross-lingual BEL benchmarks, improving Recall@1 by 4.8 to 18.2 percentage points over prior best results, without any task-specific BEL annotations. Our code and resources are available at https://github.com/AI4MedCode/BioELX.

While dense biomedical embeddings achieve strong performance, their opaque dimensions limit transparency in biomedical NLP. Recent question-based interpretable embeddings represent text through binary answers to natural-language questions, but existing approaches rely primarily on corpus-driven signals, often capturing topical or stylistic differences rather than fine-grained biomedical distinctions. We propose QIME, an ontology-grounded framework for interpretable biomedical text embeddings in which each dimension corresponds to an explicit biomedical-domain yes/no question. QIME leverages a biomedical ontology to guide contrastive question generation from semantic clusters, producing atomic, domain-grounded questions. It constructs embeddings via similarity-based semantic activation with MMR-based diversity-aware dimension selection, yielding sparse representations efficiently. Experiments on biomedical clustering, STS and retrieval benchmarks show that QIME consistently outperforms prior interpretable embedding methods and substantially narrows the gap to strong black-box biomedical encoders. It also imposes substantially lower cognitive burden than existing methods, providing concise and domain-specific interpretations. The code is available at https://github.com/L1nzh/QIME.

Conversational diagnosis requires multi-turn history-taking, where an agent asks clarifying questions to refine differential diagnoses under incomplete information. Existing approaches often rely on the parametric knowledge of a model or assume that patients provide rich and concrete information, which is unrealistic. To address these limitations, we propose a conversational diagnosis system that explores a diagnostic knowledge graph to reason in two steps: (i) generating diagnostic hypotheses from the dialogue context, and (ii) verifying hypotheses through clarifying questions, which are repeated until a final diagnosis is reached. Since evaluating the system requires a realistic patient simulator that responds to the system's questions, we adopt PatientSim, a persona-driven patient simulator, together with patient profiles from MIMIC-IV. We further adapt it with low-specificity symptom reporting to reflect how real-world patients describe symptoms vaguely during early clinical encounters. Experiments show improved diagnostic accuracy and efficiency over strong baselines, and physician evaluations support the realism of our simulator and the clinical utility of the generated clarifying questions. Our code will be released upon publication.

Understanding biomedical experiments provides a foundation for downstream tasks, e.g., laboratory automation, and facilitates effective cross-disciplinary communication. Two challenges, High Information Density (HID) and Multi-Step Reasoning (MSR), pose unique difficulties for precise experimental understanding. Extracting structured knowledge, e.g., Knowledge Graphs (KGs), is an effective approach to address the HID and MSR. However, existing biomedical datasets for structured knowledge information extraction are limited to a general or coarse-grained level, hindering fine-grained experimental understanding. To address this gap, we introduce Biomedical Protocol Information Extraction Dataset (BioPIE), a dataset providing procedure-centric KGs that capture entities, actions, and relations at a scale sufficient for reasoning across biomedical protocols. We evaluate information extraction methods on BioPIE and implement a question answering system leveraging the dataset for validation, demonstrating improved understanding performance on test sets as well as on the HID and MSR question sets.

Domain generalization has become a critical challenge in predictive healthcare, where different patient groups exhibit shifting data distributions that degrade model performance. Still, regular domain generalization approaches often struggle in clinical settings due to (1) the absence of domain labels and (2) the lack of clinical insight integration. To address these challenges in healthcare, we aim to explore how medical ontologies can be used to discover dynamic yet hierarchy-grounded patient domains, a partitioning strategy that remains under-explored in prior work. Hence, we introduce UdonCare, a hierarchy-pruning method that iteratively divides patients into latent domains and retrieves domain-invariant (label) information from patient data. On public datasets (MIMIC-III, MIMIC-IV, and eICU), UdonCare shows superiority over eight generalization baselines across four representative clinical prediction tasks with substantial domain gaps, highlighting the potential of medical knowledge for enhancing model generalization.

Hyperspectral imaging is a powerful bioimaging tool which can uncover novel insights, thanks to its sensitivity to the intrinsic properties of materials. However, this enhanced contrast comes at the cost of system complexity, constrained by an inherent trade-off between spatial, spectral, and temporal resolution. To overcome this limitation, we present a self-supervised deep learning-based approach that restores and enhances pixel resolution post-acquisition without requiring external training data beyond the images to be restored. Fine-tuned using metrics aligned with the imaging model, our physics-aware method achieves a 16$\times$ pixel super-resolution enhancement and a 12$\times$ imaging speedup without the need of additional training data for transfer learning. Applied to both synthetic and experimental data from five different sample types, including healthy and diseased tissues, we demonstrate that the model preserves biological integrity, as we did not detect systematic loss of biological features or biologically consequential hallucinations in tested datasets. We also concretely demonstrate the model's ability to reveal disease-associated metabolic changes that would otherwise remain undetectable. Furthermore, we provide physical insights into the model's inner workings, paving the way for future refinements that could potentially reveal novel high resolution features in an explainable manner. All methods are available as open-source software on GitHub.