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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2026

Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging

Episodic memory decline is a common feature of cognitively normal aging, but its extent varies markedly across individuals. Although entorhinal tau pathology is thought to be a key contributor to episodic memory impairment, the neural mechanisms linking early tau accumulation to memory differences remain unclear. Grid-cell computations in the entorhinal cortex, which provide scaffolds for organizing experiences into episodic memories, offer one candidate mechanism. Here, we combined virtual-reality functional MRI, multivariate analysis, tau PET, and delayed word-list recall in cognitively normal older adults to test whether tau-related alterations in entorhinal coding are associated with worse episodic memory. Weaker left entorhinal grid-cell-like signal was associated with poorer memory performance, and individuals with higher left entorhinal tau burden showed weaker grid-cell-like signal. This association was specific to the canonical six-fold signal and was not explained by entorhinal volume, mean diffusivity, or intracortical myelination. A cross-sectional Bayesian mediation analysis further demonstrated that bilateral medial temporal tau burden is related to memory indirectly through left entorhinal grid-cell-like signal. Together, these findings provide evidence that entorhinal grid codes may constitute a functional pathway linking tau accumulation to memory variability in normal aging.

neuroscience↗

bioRxiv2026

Simple Feedback for Complex Movement: Capturing Whole-Limb Reorganization during Single-IMU Gait Retraining

Clinical gait retraining typically relies on multi-sensor arrays and high-dimensional feedback displays, imposing setup and interpretation burdens that limit routine clinical deployment. We developed a single-IMU visual biofeedback system that delivers real-time feedback of Lower Limb Trajectory Error (LLTE), a composite kinematic error metric integrating knee position and shank angle across the stance phase. Twenty able-bodied adults walked on a treadmill under two visual biofeedback targets (flexed-knee, extended-knee) while receiving either corrected (n=10) or uncorrected (n=8) feedback, where the correction accounted for limb orientation at initial contact. LLTE and stance-phase knee kinematics adapted consistently under the flexed-knee target for both feedback groups, with feedback formulation moderating the temporal trajectory of change. Adaptation toward the extended-knee target was limited, likely because participants were already operating near terminal knee extension and because the scalar error metric provided limited directional information for correction. Ankle range of motion (ROM) changed significantly across the stance phase under both target conditions, while hip ROM did not. Multiscale multivariate sample entropy (MSMVSE) increased monotonically with time scale across all conditions, with no statistically distinguishable difference between corrected and uncorrected feedback. These results suggest that single-IMU LLTE biofeedback can modify gait mechanics and that adaptation was expressed across multiple lower-limb segments rather than through changes at a single joint.

bioengineering↗

bioRxiv2026

A Nanoheater-Integrated Fluorescence Lifetime Thermometer for Investigating Subcellular Heat Shock Factor 1 Responses

Subcellular thermal engineering provides a powerful approach for investigating and manipulating biological processes. However, existing subcellular heating platforms capable of combining spatially confined heating, quantitative thermometry and simultaneous imaging of cellular responses remain limited. We developed a quantitative nanoheater-thermometer (qNanoHT), a polymeric nanoparticle integrating a temperature-sensitive fluorescent, dye and a photothermal dye. qNanoHT determines local temperature from fluorescence lifetime using fluorescence lifetime imaging microscopy (FLIM), thereby reducing susceptibility to photobleaching, focal drift and variations in probe concentration compared with intensity-based methods. The platform enabled real-time measurement at a subcellular heat spot while the dynamics of heat shock factor 1 (HSF1) were monitored in living cells. Heating at a single intracellular site was sufficient to induce HSF1 foci. Foci induced by mild heating at approximately 38 {degrees}C dissolved after heating ceased, whereas those induced by stronger heating at approximately 41 {degrees}C persisted and were associated with caspase-3/7 activation and apoptosis. Notably, qNanoHT-mediated subcellular heating induced HSF1 foci at a lower measured temperature than uniform whole-cell heating approximately 38 {degrees}C versus 39 {degrees}C indicating that the spatial extent of heating influences the HSF1 activation threshold. qNanoHT therefore provides a quantitative platform for relating local intracellular temperature to cellular stress responses and subsequent cell fate.

bioengineering↗

bioRxiv2026

Evaluating Large Language Models as Tools to Navigate Researchers in Rapidly Evolving Research Landscapes: A Case Study in Cancer Drug Response Prediction

Large Language Models (LLMs) have emerged as promising tools for assisting researchers in automating and accelerating the synthesis of literature reviews. However, their reliability is a significant concern due to issues like factual inaccuracies and hallucinations. The key question is whether LLMs can reliably provide comprehensive, up-to-date overviews and analyses. This study evaluates the performance of three leading LLMs (OpenAI's ChatGPT, Google's Gemini, and DeepSeek) on the complex task of generating a comprehensive survey paper on deep learning for cancer Drug Response Prediction (DRP). By testing both standard and Deep Research (DR) / Deep Think (DT) modes of LLMs with prompts of varying detail, this paper assesses key academic dimensions, including reference management, content quality, and analytical depth. Key findings reveal that while DR modes of LLMs significantly improve reliability by eliminating hallucinations, performance variations exist across models and prompts. A trade-off between reference quantity and integration quality was observed, and even the best-performing models lacked the analytical depth of human experts, often requiring extensive human supervision. The study concludes that LLMs currently serve as powerful assistive tools but still cannot replace the critical validation and synthesis provided by human researchers. Choosing the best LLM to use depends on the task in hand, while several strategies can be implemented to improve the produced output.

scientific communication and education↗

bioRxiv2026

Pallidal beta oscillations underlying locomotor adaptation in Parkinsons disease

BackgroundLocomotor adaptation is essential for adjusting walking patterns to complex environments. This study investigated locomotor adaptation deficits in people with Parkinsons disease (PD) and examined oscillatory activity in the globus pallidus internus (GPi) during walking adaptation. We hypothesized that elevated beta-band activity in the GPi is associated with reduced locomotor adaptability in PD. MethodsTwelve PD patients with GPi deep brain stimulation (DBS) (eleven bilateral and one unilateral) were included. Local field potentials (LFPs) were recorded from DBS electrodes during split-belt treadmill walking. Patients were tested in the medication-off, DBS-off state. Locomotor adaptation was measured as the change in step length asymmetry during split-belt walking, with smaller changes indicating greater adaptation deficits. ResultsWe found that GPi high beta (20-30 Hz) and low gamma (30-60 Hz) oscillations were modulated during split-belt walking. Compared to adapters, non-adapters showed decreased movement-related beta suppression during walking. Across participants, beta activity in the GPi contralateral to the fast leg was negatively associated with adaptation magnitude (Spearmans {rho} = -0.65 to -0.75). ConclusionsGPi oscillations are dynamically modulated during locomotor adaptation in PD. Increased beta activity may underlie impaired sensorimotor adaptation during walking. These findings provide novel insight into basal ganglia mechanisms of gait adaptation in PD and suggest that elevated GPi beta activity may serve as a marker of locomotor adaptation deficits.

neuroscience↗

bioRxiv2026

Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.

neuroscience↗

bioRxiv2026

Cross-species analysis links cell-cell communication rewiring to NOTCH2 during serous endometrial carcinogenesis

Cell-cell interactions shape the fate of mutant cells during cancer initiation but how these interactions evolve during progression to pathologically recognizable lesions remain poorly understood. Here, we investigated cell-cell communication during serous endometrial carcinoma (SEC; also known as uterine serous carcinoma) development using a lineage-traceable mouse model and cross-species analyses of the mouse and human neoplastic endometrium. In mice, the early, pre-dysplastic stage was marked by a global decrease in inferred cell-cell interactions, followed by extensive communication network rewiring during neoplastic progression. Pathway-specific analysis revealed a similar pattern for NOTCH signaling, with NOTCH2 emerging as the dominant NOTCH receptor in Trp53/Rb1-mutant immature epithelial cells. Functionally, NOTCH2 promoted the outgrowth of more proliferative mutant organoids. Cross-species transcriptomic analysis identified conserved immature epithelial states in mouse and human neoplastic endometrial epithelium. In human tissues, NOTCH2 was overexpressed in serous endometrial intraepithelial carcinoma, a precursor of SEC, and in overt SEC. Furthermore, elevated NOTCH2 expression was associated with poor patient survival. These findings link cell-cell communication rewiring during experimental SEC development to conserved neoplastic epithelial states and identify NOTCH2 as an early marker and a potential target of disease interception.

cancer biology↗

bioRxiv2026

Aberrant accumulation of α-synuclein might be linked with the progressive motor deficits in a mouse model of Angelman syndrome

Dysfunction of maternal UBE3A leads to Angelman syndrome (AS), which is characterized by significant intellectual and motor debilities. However, the molecular underpinnings of the behavioral deficits associated with UBE3A dysfunction remain obscure. In this study, we utilized a model mouse of AS and report, for the first time, that the aberrant accumulation of -synuclein may be linked to the development of AS. Firstly, we demonstrated a progressive deterioration of various motor functions in AS mice beginning from the early adolescent phase. Subsequently, we observed an age-dependent increase in the accumulation of both soluble and insoluble -synuclein, including its pathological variant (pSer129), in the striatum and substantia nigra dopaminergic neurons of AS mice. We also found that Ube3a interacts with -synuclein and promotes its proteasome-mediated degradation, as evidenced by decreased levels of K48-linked polyubiquitinated -synuclein in the brain samples of AS mice in comparison to wild-type animals. Finally, using an RT2 Profiler PCR Array that analysed 84 genes specifically related to dopamine and serotonin pathways, we identified altered transcript level of various genes in the striatal tissues of AS mice that are commonly associated with nigrostriatal dysfunctions in Parkinson's disease. These findings highlight -synuclein as a novel target of Ube3a and suggest that -synuclein pathology may contribute to the progressive motor and other behavioral abnormalities witnessed in AS mice.

neuroscience↗

bioRxiv2026

CpxR and HicB exert independent regulatory action on the gonococcal hicAB-encoded toxin-antitoxin system

The continued emergence of Neisseria gonorrhoeae (Ng) isolates resistant to front-line antibiotics has focused efforts on understanding how alternative therapies, such as the expanded use of gentamicin (Gen), might counteract this global public health problem. Focusing on Gen as a viable alternative antibiotic for the treatment of gonorrheal infections, we previously used RNA-seq to determine if sub-lethal levels of Gen might impact gonococci on a transcriptional level and showed that expression of the putative HicA-HicB toxin-antitoxin (TA) system was increased in response to sub-lethal Gen. Importantly, loss of this TA system resulted in reduction of Ng biofilm formation in a strain specific manner. Focusing on this strain specificity, we found that the CpxR/CpxA two-component system (TCS) influences expression of the hicAB operon independently of HicB autoregulation. We now report that CpxR selectively binds to the hicAB operon to enhance expression of hicAB but does not interfere with binding of HicB to the promoter region. Furthermore, we show that single base pair differences in the intergenic region between hicA and hicB impact regulation by CpxR. Hence, the regulation of the HicAB TA in gonococcal strains is a highly coordinated response that can involve autoregulation by HicB and the CpxRA TCS. We propose that this dual regulatory scheme maximizes the ability of Ng to respond to Gen and hostile environmental conditions.

microbiology↗

bioRxiv2026

Adolescent blockade of complement signaling in the lateral septum increases social novelty seeking behavior in male mice

Social behaviors are critical for survival and change dramatically over the lifespan. Adolescence is a critical period of development during which social novelty seeking peaks before declining into adulthood. Adolescence is also a time of pronounced neural circuit refinement as excess synapses are eliminated. One critical mechanism supporting this maturation of neural circuits is microglial pruning of synapses through the classical complement signaling cascade. However, it remains unclear how microglial pruning of the neural circuitry supporting social novelty preference shapes the trajectory of this behavior during adolescence. To address this, we blocked microglial complement-dependent pruning during adolescence by injecting neutrophil inhibitory factor (NIF; blocks the adhesion of ligands to CD11b/C3 receptor) in the lateral septum (LS), a key node in the social circuitry supporting social novelty preference, in male mice. We found that NIF administration into the LS during adolescence increased preference for the novel social chamber over the familiar as compared to control PBS administration. LS-NIF treatment had no impact on anxiety-like behavior in the light-dark box test and no effect on sociability. LS-NIF treatment also decreased the expression of immune-related genes in the LS as compared to PBS treatment. These data support the hypothesis that complement-dependent microglial synaptic elimination in the LS is critical for the developmental progression of social novelty preference.

neuroscience↗

bioRxiv2026

POU2AF2/OCA-T1 coactivates POU2F2 and defines a lineage-specific dependency in diffuse large B-cell lymphoma

Lineage-restricted transcriptional programs establish cell identity and can create selective dependencies in cancer. Here, we identify POU2AF2, encoding the transcriptional co-activator OCA-T1, as a critical lineage-specific dependency in a subset of diffuse large B-cell lymphoma (DLBCL). Pan-cancer dependency analyses and patient cohorts reveal elevated POU2AF2 expression in genetically aggressive DLBCL, where its depletion markedly suppresses tumor growth in vitro and in vivo. Mechanistically, POU2AF2 cooperates with the B-cell lineage-defining transcription factor POU2F2 (OCT2) to activate lymphocyte activation gene programs through direct chromatin engagement, thereby sustaining malignant transcriptional networks. We further identified a key epigenetic regulatory axis composed of the lineage-specific transcription factor TCF3 and the histone methyltransferase SET1A-COMPASS that drives POU2AF2 expression downstream of B-cell receptor signaling. Single-cell transcriptomic analysis reveals that POU2AF2 marks and sustains an innate-like B1 B-cell population in vivo, a candidate cell of origin for lymphoma. Together, these findings define a lineage-restricted POU2AF2/POU2F2 transcriptional module, controlled by a TCF3/SET1A epigenetic network, that sustains both innate-like B-cell identity and malignant fitness in DLBCL. Our study uncovers a previously unrecognized lineage-specific transcriptional dependency and highlights POU2AF2 and its associated regulatory circuitry as potential therapeutic targets in aggressive B-cell malignancies.

cell biology↗

bioRxiv2026

An agent-based 3D model of non-genetic adaptation in cancer tissues under electrical, mechanical, and hypoxic stress

Non-genetic adaptation enables cancer cells to alter their phenotype under stress without requiring new mutations. However, the mechanisms by which electrical, mechanical, and hypoxic cues combine to shape this process in 3D tissues remain poorly understood. This work presents an agent-based tumor model that integrates vascular oxygen supply, a globally imposed electric field, mechanically mediated crowding and compression cues, phenotype transitions, cell growth, mitosis, death, and inheritance of adaptive memory across division. The simulated tumors exhibit a three-stage trajectory consisting of necrosis onset, transient collapse of live mass, and partial regrowth accompanied by progressive accumulation of adapted cells. Continuous electrical stimulation produces a dose-dependent reduction in live mass while markedly increasing the adapted fraction, with comparatively limited changes in final necrotic burden. This response is strongly conditioned by mechanics and reshapes (and is reshaped by) adaptive capacity. Pulsed stimulation further shows that, in the model, electric field amplitude and temporal schedule jointly determine memory phenomena, phenotypic diversification, and growth recovery. These results show that coupling local oxygen availability, mechanical constraints, electrical forcing, and history-dependent phenotype transitions can generate distinct tissue-level patterns of phenotypic heterogeneity. Both stimulus magnitude and temporal protocol influenced the resulting population structure, suggesting that the history of physical stress may be an important determinant of adaptive dynamics in spatially organized tumor models.

biophysics↗

bioRxiv2026

Programmable Antibody-DNA Conjugation via HUH-Tags Enables Quantitative Measurement of Receptor-Specific Adhesion Dynamics

Antibody-DNA oligonucleotide conjugates (AOCs) are widely used for molecular assembly and cellular analysis, yet current approaches for generating these conjugates often rely on nonspecific chemistries that produce heterogeneous products. Here, we present two complementary strategies for generating site-specific AOCs using covalent DNA-linking HUH endonucleases. In one approach, recombinant antibodies are genetically fused to HUH-tags to enable direct, site-specific DNA conjugation. In the second, off-the-shelf antibodies are indirectly linked to HUH-tags using a photocrosslinkable Protein G-HUH fusion, enabling covalent Fc-directed attachment. Both strategies yield homogeneous AOCs while preserving antigen binding affinity. We apply these conjugates to a DNA-based mechanochemical assay, termed rupture-and-deliver tension gauge tethers (RAD-TGTs), which converts receptor-mediated adhesion forces into intracellular delivery of a fluorescent oligonucleotide payload. By tuning duplex stability, we define adhesion dynamics across multiple mechanical regimes. Using HER2- and beta1-integrin-targeting AOCs, we identify receptor-specific adhesion signatures and uncover cooperative interactions between receptor systems in a panel of cancer cell lines. Dual-color probes enable multiplexed single-cell mechanical phenotyping, and application to primary NK cells reveals dose-dependent responses to integrin modulators. These results establish a generalizable platform for site-defined AOC generation and for quantitative, high-throughput measurement of receptor-mediated adhesion dynamics.

bioengineering↗

bioRxiv2026

Embedding wear assessment in musculoskeletal simulation: A proof-of-concept application to total hip arthroplasty

Predicting wear in artificial joints requires integrating joint dynamics, contact mechanics and progressive surface evolution, yet these processes are often treated separately. In total hip arthroplasty (THA), finite-element approaches remain the reference standard, but they are computationally demanding and usually rely on boundary conditions from independent musculoskeletal (MSK) models, hindering consistent coupling and feedback between wear progression and movement dynamics. As a single-subject proof of concept, we present a computational framework that embeds wear estimation within forward MSK simulations through OpenSim-MATLAB integration. Contact variables are computed using an elastic-foundation formulation, and wear is updated through the Archard law, enabling cyclic prediction of contact mechanics and surface evolution within a single workflow at practical computational cost. The framework was evaluated in one subject with right THA during five activities of daily living and numerically benchmarked against finite-element simulations. A long-term walking analysis of 4 million cycles was also performed to assess geometry updating. Across tasks, peak contact pressures remained within 7% of finite-element predictions. Linear wear depth and volumetric loss showed maximum deviations of 16% and 13%, respectively. Accounting for progressive geometry changes yielded a maximum wear depth about 31% lower than linear extrapolation. These preliminary results support the framework's computational feasibility and numerical consistency for the tested case; nevertheless, multi-subject evaluation is required before broader predictive or clinical use.

bioengineering↗

bioRxiv2026

Hormetic heat shock activates HLH-30/TFEB independently of canonical nutrient-sensing pathways

In Caenorhabditis elegans, a brief, sublethal heat shock (HS) induces a hormetic response that increases resistance to subsequent stress and extends lifespan. These benefits require hlh-30, the ortholog of mammalian transcription factor EB (TFEB). Although HS induces robust HLH-30 nuclear translocation, how this response is regulated remains poorly understood. Nutrient- and energy-sensing pathways, including mTORC1 and AMPK, regulate HLH-30/TFEB subcellular localization under other physiological conditions, but whether they mediate its nuclear translocation during HS is unknown. Here, we show that, although HS inhibited mTORC1 and dephosphorylated its conserved HLH-30 S201 target site, HLH-30 S201 phosphorylation was dispensable for HS-induced HLH-30 nuclear localization and hormetic protection. Moreover, HS remained protective in hlh-30 mutants when mTORC1 activity was reduced, revealing an HLH-30-independent component of the hormetic response. HS also activated AMPK and aak-2 was required for hormetic protection but dispensable for HS-induced HLH-30 nuclear localization and autophagosome formation. Together, these findings demonstrate that although HS engages canonical mTORC1 and AMPK signaling, these pathways do not account for HS-induced HLH-30 nuclear localization and instead make distinct contributions to hormetic protection. Our findings reveal stress-specific regulation of HLH-30/TFEB and point to additional mechanisms that drive its activation during heat stress.

cell biology↗

bioRxiv2026

Structural characterization the LlaI anti-phage defense system reveals insights into the evolution of nucleotide specificity and the organization of DNA binding in McrBC restriction complexes

Canonical McrBC enzymes are nucleotide-powered, motor-driven endonucleases that bind and cleave modified bacteriophage DNA. Non-canonical McrBC homologs like LlaI and BsuMI are distinguished by a unique three-gene organization and the ability to target DNA site-specifically. Here, we report the atomic-resolution crystal structures of the DNA-binding module LlaI.R1 and AAA+ motor LlaI.R2 from the Lactococcus lactis LlaI anti-phage defense system. The crystallized LlaI.R2 hexamer traps two distinct active site conformations that correlate to different states of the nucleotide hydrolysis cycle and reveal that the organization of the critical catalytic machinery present in canonical McrB homologs is also conserved in non-canonical R2 proteins. Although canonical McrB homologs are strictly GTP-specific, we find that the R2 proteins from LlaI and BsuMI do not discriminate between different nucleotides, even when in complex with their respective R1 partners. Using mutagenesis, we define surfaces on the LlaI.R1 structure that are critical for DNA-binding and interaction with LlaI.R2. These observations support computational modelling of the assembled LlaI restriction system bound to DNA. Together, our data provide new insights into the evolution of nucleotide specificity in McrBC restriction complexes and the molecular mechanisms governing McrBC-catalyzed DNA translocation and cleavage.

biochemistry↗

bioRxiv2026

Integrative single cell analysis of CD8+ T-cells across early and advanced oral cancers reveals signatures of anti-tumour activity

Tumour-targeting CD8 T cells drive responses to every major form of cancer immunotherapy. Identifying them, however, remains an unsolved problem in solid tumours. The antigens they recognize are rarely defined and almost never shared between patients. We profiled 51,459 CD8+ T cells by paired single-cell RNA and T-cell receptor sequencing across 28 samples from 17 HPV-negative oral cancers spanning primary tumours, draining lymph nodes, metastases, and pembrolizumab-treated recurrences. We found that clonotypes that were expanded and shared across anatomical sites and timepoints were enriched within tumours and progressively selected over disease evolution and checkpoint blockade. Designating these shared-expanded clones as putative tumour-targeting cells, we trained a machine learning classifier that identifies them from transcriptome data alone. This 108-feature random forest signature recapitulated programmes of tumour reactivity and generalized to an integrated atlas of 89,318 CD8+ T cells from independent cohorts, showing progressive enrichment from normal to malignant tissue, and localized to tumour-proximal niches in spatial transcriptomics. By demonstrating that clonal behaviour across space and time encodes tumour reactivity in the transcriptome, this work establishes a generalizable framework for mapping tumour-engaged immunity without knowledge of the underlying antigen.

cancer biology↗

bioRxiv2026

Automatic bioinformatic software named entity recognition from literature

Bioinformatics software and databases are essential components of modern life science research, yet their mentions in the scientific literature are often inconsistent and difficult to systematically identify at scale. The lack of a comprehensive and up-to-date catalog of bioinformatics resources hinders efforts toward automated biomedical knowledge extraction and streamlined data analysis. Here we present SNAIL, a hybrid named entity recognition framework designed to automatically identify bioinformatics software and database (SW/DB) names from biomedical texts. SNAIL integrates complementary lexical and semantic modeling strategies. The lexical component captures orthographic patterns and contextual cues characteristic of SW/DB names, while the semantic component leverages contextual embeddings generated by transformer-based language models such as SciBERT, combined with an explicit token-masking strategy to enhance entity-focused representations. A large training corpus was constructed automatically through a hybrid pipeline that integrates citation-hinted extraction with large language model-assisted distillation. Evaluation on two independent benchmark datasets and real-world research articles demonstrates that SNAIL substantially outperforms existing approaches, including domain-specific methods such as bioNerDS2 and general-purpose large language models such as ChatGPT, Gemini, Grok and Claude. Applying SNAIL to large-scale literature analysis further reveals distinct journal-level preferences across bioinformatics subfields. These results demonstrate that SNAIL provides an accurate and scalable solution for identifying bioinformatics resources in scientific texts and enables systematic meta-analysis of tool usage and research trends.

bioinformatics↗