Biology subjects

Kim, S.

Publications and source records attributed to Kim, S..

At least 127 records · Page 7Linked to original sources

bioRxiv2026

Age-Dependent Chromatin Remodeling Drives Inflammatory Dysregulation in Tendon Cells

Aging impairs tissue function and tolerance to cellular stress by reprogramming the behavior of resident cells. With global increases in lifespan, the prevalence of chronic and degenerative musculoskeletal disorders, including tendon degeneration, continues to rise; however, effective interventions to counteract age-related decline remain limited. Here, we investigate how a central age-associated stressor, inflammation, differentially modulates tendon cell behavior derived from young and mature-aged donors. Using super-resolution microscopy to resolve nanoscale chromatin organization in conjunction with epigenomic and transcriptomic profiling, we identify age-dependent regulatory mechanisms that govern inflammatory responsiveness. Mature-aged tendon cells exhibit exaggerated pro-inflammatory and catabolic responses across chromatin, gene expression, and protein signaling levels, characterized by enhanced TNF receptor organization, elevated accessibility at pro-inflammatory regulatory elements, and robust induction of matrix-degrading enzymes. Notably, the AP-1 transcription factor family emerges as a central age-dependent regulator, displaying distinct motif accessibility patterns that bias mature tenocytes toward inflammatory and degenerative transcriptional programs. Taken together, our findings demonstrate that age-dependent epigenetic priming amplifies inflammatory sensitivity and constrains reparative gene regulation in mature tendon cells. This work provides a mechanistic framework linking chromatin remodeling to tendon degeneration and holds potential to identify epigenetic and transcriptional pathways as potential targets for rejuvenation strategies in aging musculoskeletal tissues.

bioengineering↗

bioRxiv2026

A prelimbic molecular clock of protein synthesis for memory persistence

Emotionally salient associative memories can endure for long periods, yet the mechanisms that determine their long-term stability remain unclear. Here we show that the prelimbic (PL) cortex integrates temporally structured translational programs to control both the consolidation and reconsolidation of cued threat memories. Using Pavlovian threat conditioning with in vivo fiber photometry, we found that PL calcium dynamics tightly track memory strength: discrete threat-predictive cues evoked robust activity during recent and single-timepoint remote retrieval, whereas prior retrieval selectively weakened remote expression, independent of contextual influences. Translational profiling of PL Camk2a cells uncovered a biphasic consolidation program, with an early phase characterized by ER stress-linked translational repression and robust oligodendrocyte plasticity, followed by a delayed phase engaging synaptic growth pathways. Loss- and gain-of-function approaches demonstrated that eIF2-regulated, cap-independent translation is essential for recent consolidation and for the enduring stabilization of remote memory, whereas retrieval-induced destabilization engages a mechanistically distinct, eIF4E-dependent translational pathway required for reconsolidation. These findings identify the PL cortex as a dynamic node in which discrete modes of translational control govern the long-term persistence of emotional memories.

neuroscience↗

bioRxiv2025

APE1 Coordinates Its Disordered Region and Metal Cofactors to Drive Genome Surveillance

Efficient recognition of DNA lesions such as apurinic/apyrimidinic (AP) sites is essential for maintaining genome stability. Apurinic/apyrimidinic endonuclease 1 (APE1) is the primary eukaryotic AP endonuclease, yet how it identifies rare lesions among vast stretches of undamaged DNA remains incompletely understood. Using single-molecule imaging combined with molecular dynamics simulations, we reveal that APE1 employs a distinctive dual mechanism to search DNA. First, Mg{superscript 2} coordination at the active site neutralizes clustered negative charges, stabilizing electrostatic contacts during scanning. Second, its N-terminal intrinsically disordered region (IDR)--a feature conserved only in eukaryotic homologs but absent in prokaryotic ExoIII--not only forms DNA through transient IDR contacts but also engages continuous interactions via the unprecedented 177 arginine residue within the structured nuclease domain, thereby prolonging residence time and enabling long-range diffusion. Together, these two modules synergize to promote a sliding-based search strategy tailored to the complexity of eukaryotic genomes. Consistent with this model, IDR deletion restricts APE1 to 3D collisions, whereas IDR duplication enhances 1D scanning. Thus, APE1 exemplifies how structural disorder and metal-ion coordination integrate to enable long-range lesion recognition, highlighting an evolutionary innovation in eukaryotic DNA repair.

molecular biology↗

bioRxiv2025

Neural Mechanisms of Willed Attention Control

Cueing paradigms are commonly used to study the neural mechanisms of visual spatial attention control. In these paradigms, each trial starts with an external cue, which instructs the subject to pay covert attention to a spatial location in anticipation of an impending stimulus (instructed attention). Recent work has introduced a new type of cue which prompts the subject to spontaneously decide which spatial location to attend (willed attention). We studied the neural mechanisms of willed attention control by analyzing fMRI and EEG data recorded at two institutions (UF and UC Davis) using the same willed attention paradigm. The findings include: (1) both instructional cues and the choice cue activated the DAN, (2) the choice cue additionally activated a frontoparietal decision network consisting of dorsal anterior cingulate cortex (dACC), anterior insula (AI), anterior prefrontal cortex (APFC), dorsal lateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL), (3) the decision about where to attend can be decoded in frontoparietal decision network in choice trials but not in instructional trials, and (4) EEG alpha oscillation patterns immediately preceding the choice cue, but not the instructional cues, predicted the postcue direction of attention and the frontoparietal decision network activity. Based on these findings we proposed a model of willed attention control suggesting how the direction of visual spatial attention was decided upon in the absence of external instructions.

neuroscience↗

bioRxiv2025

Functional modules predict cancer-relevant genetic interactions in mammalian cells

Genetic interactions can reveal gene function and identify disease-relevant synthetic lethals, but resource-intensive screening in human cells constrains experimental scope and limits our understanding of how generalizable sparse hits are. Here, we leverage principles from yeast genetic networks to identify human gene modules involved in receptor tyrosine kinase signaling and DNA damage response that are predicted to be enriched for genetic interactions, then use our enCas12a-based In4mer combinatorial knockout platform to efficiently screen these modules across diverse cancer cell lines. We identify hundreds of unreported synthetic lethals, including a dense network within the protein N-linked glycosylation machinery that shows both evolutionary conservation and network rewiring, and we confirm that interactions discovered in 2D cell culture are maintained in more physiologically relevant models. Critically, a meta-analysis within and between screens highlights sources of variation in published results, reveals the potential for false positives in screens with many essential genes, and demonstrates the need to move beyond DDR for actionable synthetic lethalities.

systems biology↗

bioRxiv2025

Organelles harbour pH gradients

Organelle pH is critical to organelle identity and function. Resident proteins that define each organelle modify transiting cargo proteins, with both retention and trafficking between organelles governed by pH-dependent mechanisms. For example, lysosomal enzymes bind mannose-6-phosphate receptors at the higher pH ([~]6.5) of the Golgi and dissociate at the lower pH ([~]5.5) of late endosomes1. Proteins that stray from the endoplasmic reticulum (ER) are captured by KDEL receptors in the acidic Golgi and returned into the neutral ER2,3. This pH-tuned trafficking system compartmentalizes organelle function and prevents mis-localization of critical enzymes4. Dysregulated organelle pH disrupts their function and leads to various diseases. Because protons move rapidly in water, the pH within a single organelle is currently assumed to be spatially uniform5. Here, using a reporter sensitive from pH 5.5 - 10.5 to map a spectrum of organelles at high resolution, we discovered that pH gradients exist within single, large or long organelles such as the ER and mitochondria, and in membrane-less organelles without ion-transporting proteins such as the nucleolus. These new findings upend our understanding of organellar pH, prompting new questions about proton diffusion within the cell, and its potential consequences on organelle function.

cell biology↗

bioRxiv2025

A Novel Patient-Derived Mutation in Glucocorticoid Receptor Reveals an Essential Role for DNA binding in Development and Endocrine Regulation

Glucocorticoid receptors (GRs) are vital transcription factors regulating stress responses, metabolism, and development. We report here a novel heterozygous NR3C1 c.1310C>T (p.T437I) variant within the GR DNA-binding domain found in a family exhibiting clinical and hormonal manifestations of partial glucocorticoid resistance. Patient-derived fibroblasts demonstrated an overall suppression in dexamethasone-induced transcription. To comprehensively assess the significance of the variant, we engineered a knock-in mouse model (Nr3c1+/T444I mice) using CRISPR-Cas9, providing an in vivo model of the patient-derived GR mutation at the orthologous residue. Heterozygous mice exhibited partial glucocorticoid resistance, dysregulated HPA axis activity and impaired dexamethasone suppression, closely recapitulating the patient phenotype. Homozygous Nr3c1T444I/T444I embryos were recovered at embryonic day 12.5 (E12.5) but did not survive to term, indicating mid-gestational lethality. Transcriptomic profiling of primary mouse embryonic fibroblasts revealed dosage-dependent effects with heterozygotes showing an intermediate response to dexamethasone compared to wild-type, while homozygotes showed a markedly blunted response. Our results challenge prior assumptions by demonstrating that GR DNA-binding is essential for embryogenesis, while offering a new preclinical platform to investigate glucocorticoid resistance pathophysiology and therapeutic interventions.

genetics↗

bioRxiv2025

Rare longevity-associated variants, including a reduced-function mutation in cGAS, identified in multigenerational long-lived families

Life expectancy has steadily increased in the last two centuries, while healthspan has been lagging behind. Survival into extreme ages strongly clusters within families which often exhibit a delayed onset of (multi)morbidity, yet the underlying protective genetic mechanisms are still largely undefined. We performed affected sib-pair linkage analysis in 212 sibships enriched for ancestral longevity and identified four genomic regions (LODmax [≥]3.0) at 1q21.1, 6p24.3, 6q14.3, and 19p13.3. Within these regions, we prioritized 12 rare protein-altering variants in seven candidate genes (NUP210L, SLC27A3, CD1A, CGAS, IBTK, RARS2, and SH2D3A) located in longevity-associated loci. Notably, a missense variant in CGAS (rs200818241), was present in two sibships. Using human- and mouse-based cell models, we showed that rs200818241 reduced protein stability and attenuated activation of the canonical cGAS-STING pathway in a cell-type specific manner. This dampened signalling mitigated inflammation and delayed cellular senescence, mechanisms that may contribute to the survival advantage of CGAS variant carriers. Our findings indicate novel rare variants and candidate genes linked to familial longevity and highlight the cGAS-STING pathway as a potential contributor to the protective mechanisms underlying human longevity.

genetics↗

bioRxiv2025

Co-targeting KRAS and Exportin1 as an effective therapeutic strategy for KRASG12D mutant pancreatic ductal adenocarcinoma

BackgroundSeveral KRASG12D inhibitors (KRASG12Di) are under clinical evaluation for pancreatic ductal adenocarcinoma (PDAC). However, as seen with other first generation KRAS inhibitors, resistance may limit their long-term efficacy, necessitating combination strategies to enhance therapeutic outcomes. Exportin 1 (XPO1), a nuclear transport protein overexpressed in PDAC, represents a therapeutic vulnerability in KRAS-mutant cancers. Here, we demonstrate that the second-generation XPO1 inhibitor Eltanexor synergizes with MRTX1133 to enhance its efficacy in multiple PDAC models. MethodsWe generated KRASG12Di-resistant PDAC cells and assessed their response to Eltanexor. The antiproliferative effects of MRTX1133 and Eltanexor combinations were evaluated in 2D and 3D in vitro PDAC models. The in vivo efficacy of the combination was tested in KRASG12D-mutant human and murine PDAC xenograft and allograft models. ResultsEltanexor sensitized MRTX1133-resistant PDAC cells to growth inhibition. In both 2D and 3D culture models, the combination of Eltanexor and MRTX1133 significantly reduced cell viability. Mechanistically, the combination treatment suppressed key KRAS downstream signaling molecules, including p-ERK, mTOR, p-4EBP1, DUSP6, and cyclin D1. Kinome analysis further revealed reduced MAPK-related kinase activity. Combining subtherapeutic doses of Eltanexor and MRTX1133 resulted in significant tumor regression and prolonged survival in PDAC xenograft and immunocompetent orthotopic allograft models. Moreover, maintenance therapy with Eltanexor prevented tumor relapse, yielding a durable antitumor response. ConclusionThis study demonstrates that Eltanexor overcomes resistance to MRTX1133 and enhances its efficacy in PDAC. The combination regimen may provide a durable therapeutic response while reducing the required dose of KRASG12D inhibitors, potentially delaying resistance and improving patient outcomes. Statement of Translational RelevancePDAC remains one of the deadliest malignancies, with limited effective therapies and dismal survival rates. The emergence of KRASG12D-selective inhibitors, such as MRTX1133, marks a critical advance for nearly 40% of PDAC patients harboring this oncogenic driver. However, inevitable emergence of adaptive or acquired resistance to KRAS inhibitors remains a major barrier to achieving durable clinical benefit. This study uncovers XPO1 inhibition as a rational and synergistic strategy to augment the antitumor efficacy of MRTX1133. By enhancing KRASG12D inhibitor activity and potentially reducing the required therapeutic dose, this combination approach offers a novel means to delay or overcome resistance. These findings provide a strong preclinical rationale for clinical trials evaluating KRAS inhibitors in combination with XPO1 inhibitors and may significantly improve outcomes for a substantial subset of PDAC patients who currently lack effective targeted treatment options.

cancer biology↗

bioRxiv2025

Exclusive ipsilateral representation of sequential tactile differences challenges contralateral dominance

Tactile perception has long been thought to be processed primarily in the contralateral somatosensory (S1), yet the functional role of ipsilateral S1 in human tactile discrimination remains unclear. We designed an fMRI experiment to investigate the neural representation of sequential vibrotactile discrimination as participants judged which of two successive stimuli delivered to the fingertip was higher in frequency. Contralateral S1 showed robust activation during unilateral stimulation, whereas ipsilateral S1 exhibited overall suppression. Interestingly, we found reliable frequency-dependent modulation in ipsilateral S1, which was absent in a control condition requiring no comparison between stimuli. Multivariate representational analyses further demonstrated that the difference in the neural representations between successive stimuli was strengthened under memory demands, particularly within ipsilateral S1 and parietal cortices. The ipsilateral representation was observed for stimulation of either hand, suggesting a bilateral and symmetric encoding mechanism rather than a hand-specific effect. Together, these findings demonstrate that the ipsilateral S1 contributes to tactile discrimination despite its overall suppression during unilateral stimulation, challenging classic contralateral models of somatosensory processing. Our results highlight interhemispheric coordination as a key mechanism underlying perceptual decisions.

neuroscience↗

bioRxiv2025

Olfactory biopsy analysis of Alzheimer's pathobiology across disease stages

Alzheimers Disease (AD) is a neurodegenerative condition affecting millions worldwide. Defining early pathobiological events remains challenging, in part due to inaccessibility of neural tissue. Because olfactory neurons are accessible, and olfactory loss is prevalent in AD, we evaluated olfactory brush biopsies from controls, individuals with cerebrospinal fluid (CSF) biomarker-confirmed AD, and cognitively typical individuals whose positive biomarkers signal a pre-clinical AD stage. We define via single cell RNA-sequencing (n=22 subjects) conserved neuroinflammatory T cell, myeloid, and olfactory neuron changes detectable even in pre-clinical AD subjects. Activated memory T cell states were a hallmark of pre-clinical AD, paralleling CSF T cell phenotypes seen in advanced disease, accompanied by both microglia-like inflammatory programs and olfactory neuron inflammatory injury. Together, our findings establish a novel platform permitting analysis of neural tissue in AD at its earliest stages.

neuroscience↗

bioRxiv2025

3D Hybrid Bioprinting for Complex Multi-Tissue Engineering

3D bioprinting has revolutionized tissue engineering, enabling intricate, physiologically relevant constructs unattainable with conventional techniques, yet it remains limited in integrating soft and rigid multifunctional components for complex multi-tissue applications. In this study, we introduce a 3D hybrid bioprinting approach implementing the Hybprinter platform, which integrates multiple 3D printing modules under optimized conditions for a continuous bioprinting process with multiple soft and hard biomaterials. This approach demonstrates robust biocompatibility and broad tissue engineering potential for modeling and therapeutic applications. The capacity to fabricate multi-hydrogel hybrid constructs is illustrated by representative examples highlighting vascularization, multifunctionality, mechanical robustness, and implant suturability. Notably, compared with commonly fabricated hydrogel-only constructs, the resulting hybrid constructs achieve over a 1000-fold increase in mechanical strength, and demonstrated enhanced osteogenic differentiation, underscoring their suitability for load-bearing musculoskeletal and orthopedic tissue engineering. Additionally, cell-laden hydrogel constructs demonstrated robust chondrogenic differentiation, highlighting the capacity for lineage-specific tissue development in vitro. Beyond these outcomes, the presented hybrid bioprinting approach integrates essential tissue engineering attributes that unites mechanical robustness and suturable capacity with multi-material integration, gradient property design, incorporation of bioactive agents, and support for multi-cell loading. This versatile platform advances complex tissue engineering and holds promise for patient specific, organ-on-demand applications.

bioengineering↗

bioRxiv2025

When Animals Turn Inside Out: The Eversion of Bloodworms

Bloodworms, Glycera dibranchiata, possess an eversible proboscis that normally remains concealed within their bodies but explosively everts if the worm attacks or burrows. How does the bloodworm evert quickly and reliably? In a series of experiments, we characterize bloodworm kinematics, pressure, and material properties to estimate the criteria for eversion safely without rupture of the proboscis. We predict the proboscis can withstand pressures 50 times higher and bending strains up to three times higher than the respective values observed. We also present a dimensional analysis of eversion, finding that everting animals, from frogs to snails to sharks, do not satisfy Froudes law for equivalence of velocities. Our findings may help inspire the development of pressure-driven soft robots with efficient retraction capabilities.

biophysics↗

bioRxiv2025

T cell costimulatory and inhibitory signals differentially modulate LAT condensate nucleation propensity after TCR ligation

Linker for activation of T cells (LAT) is a membrane-surface scaffold protein that assembles key signaling molecules upon T cell receptor (TCR) activation. Recent observations have revealed LAT assembly occurs in discretized condensates traceable to single molecular TCR activation events. Moreover, the condensation process occurs abruptly, but after a distinct delay, indicative of a type of phase transition. Here we examine the effects of costimulatory (CD80, CD86) and inhibitory (PD-L1) ligands on the nucleation propensity of LAT condensation. We utilize single molecule mobility tracking to resolve the moment a pMHC molecule binds to TCR combined with intracellular imaging to measure the time delay between pMHC:TCR binding and nucleation of the corresponding LAT condensate. These delay time distributions reflect the propensity function for stochastic nucleation of the LAT condensate and provide a measure of the effective signal strength from a single, activated TCR. The results reveal that CD28 stimulation by CD80 or CD86 causes a distinct reduction in the mean delay time to LAT condensation while PD-L1 is mildly antagonistic to the process. Collectively, these observations strengthen evidence that probability and timing of the LAT nucleation process itself is tightly associated with signal propagation downstream from individual TCR activation events.

biophysics↗

bioRxiv2025

Identifying the therapeutic potential of Niclosamide in overcoming IFN-gamma dependent cancer immune evasion in the Tumor Microenvironment

BackgroundTumor cells frequently develop immune resistance through interferon-{gamma} (IFN-{gamma})-induced PD-L1 expression, acquisition of cancer stem cell (CSC)-like features, and adaptation to hypoxia within the tumor microenvironment (TME). Although IFN-{gamma} activates both STAT1 and STAT3, how these pathways interact to regulate immune evasion under hypoxia remains unclear. MethodsUsing the MC38 murine colorectal cancer model and T cell-tumor spheroid co-culture assays, we examined how IFN-{gamma} signaling through STAT1 and STAT3 influences PD-L1 expression, CSC plasticity, and cytotoxic T cell function under normoxic and hypoxic conditions. Pharmacologic inhibitors and siRNA knockdown were used to dissect pathway function, and Niclosamide, an FDA-approved anthelmintic, was evaluated as a dual STAT1/STAT3 inhibitor. ResultsWe found that IFN-{gamma} primarily induced PD-L1 through STAT1 activation, while CSC plasticity was associated with STAT3 signaling. STAT1 and STAT3 displayed reciprocal regulation--blocking one enhanced activation of the other. Niclosamide effectively inhibited phosphorylation of both STAT1 and STAT3, which led to suppressed PD-L1 upregulation and reduced CSC enrichment. In addition, it also partially inhibited hypoxia-induced HIF-1 expression. In co-culture assays, Niclosamide improved T cell infiltration and reduced exhaustion under hypoxic conditions, resulting in improved T cell killing. ConclusionsOur findings identified Niclosamide as a potent dual STAT1/3 inhibitor capable of reversing IFN-{gamma} and hypoxia-driven immune evasion. Repurposing Niclosamide may represent a promising strategy to enhance the efficacy of immune checkpoint blockade in solid tumors. key messagesInterferon-{gamma} (IFN-{gamma}) enhances cytotoxic T cell function but also promotes tumor immune evasion by upregulating PD-L1 and inducing cancer stem cell- like properties. Our study identifies a reciprocal regulatory mechanism between STAT1 and STAT3 in IFN-{gamma}-treated tumor cells that shapes immune evasion outcomes. We demonstrate that Niclosamide, an FDA-approved anthelmintic, acts as a dual STAT1/STAT3 inhibitor, effectively suppressing PD-L1 induction, limiting cancer stemness, and reducing HIF-1 expression under hypoxia. Niclosamide also restores T cell infiltration and decreases exhaustion in a 3D tumor spheroid model. By repurposing Niclosamide, this work provides a feasible approach to enhance the efficacy of immune checkpoint blockade and guide future translational and clinical studies in immunotherapies against solid tumors.

immunology↗

bioRxiv2025

Oncogenic and immunomodulatory functions of SUV420H1 in HPV-negative head and neck squamous cell carcinoma.

Despite the advent of immunotherapy, human-papilloma-virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) carries a high morbidity and mortality rate, thus novel therapies are urgently needed. Suppressor Of Variegation 4-20 Homolog 1 (SUV420H1) is a protein lysine methyltransferase that writes H4K20me3. Approximately 35% of HPV-negative HNSCC tumors carry gains/amplifications of SUV420H1. Gene Set Enrichment Analysis (GSEA) showed enrichment of proliferation-, epithelial-mesenchymal transition (EMT)- and immune-response pathways in SUV420H1-overexpressing HPV-negative HNSCC tumors. Depletion of SUV420H1 led to decreased proliferation, cell cycling and invasion in human HPV-negative HNSCC cell lines, while enzymatic inhibition decreased the invasive capacity but not the proliferation and cell cycling of HPV-negative HNSCC cell lines, supporting the presence of catalytically-independent and -dependent functions of SUV420H1. In a syngeneic mouse model of mouse oral carcinoma 1 tumors (MOC1), Suv420h1 knockout (KO) in MOC1 cancer cells halted tumor growth and synergized with anti-PD-1 therapy. In the tumor immune microenvironment (TIME) of Suv420h1 KO MOC1 tumors, a significant increase in the macrophage compartment with a concurrent decrease in the protumorigenic granulocytic myeloid derived suppressor cells (gMDSCs) was observed. Genome-wide mapping of SUV420H1-mediated H4K20me3 revealed enrichment of EMT-, IFN-response, and myeloid-attracting chemokines. This work provides rationale for the depletion/degradation of SUV420H1 as a novel therapeutic strategy to hinder proliferation and invasion, and to impart sensitization to anti-PD-1 immunotherapy for patients with HPV-negative HNSCC tumors with SUV420H1 gain/amplification.

cancer biology↗

bioRxiv2025

Space-efficient method for high-throughput generation of uniform cell-laden hollow agarose microcapsules

Hollow hydrogel microcapsules isolate cells while allowing diffusion of nutrients and factors, supporting applications from single-cell analysis and clonal expansion to spheroid formation inside them. Conventional encapsulation relies on bulky instruments such as pumps and pressure controllers, hindering use in confined environments such as anaerobic chambers. Here we present a space-efficient method combining pump-free, -20 kPa negative-pressure droplet generation with particle-templated emulsification to produce millions of [~]70 {micro}m hollow agarose microcapsules using only a sealed bottle and a vortex mixer within a 30 cm x 30 cm footprint. The system maintains [~]491 {+/-} 2 drops/s and yields (2.26 {+/-} 0.09) x 106 capsules per batch with CV < 4% (N = 3). Operating entirely inside an anaerobic chamber, we encapsulated mouse gut bacteria and quantified population-level proliferation over four days. This space-efficient workflow enables high-throughput encapsulation under spatial constraints such as biosafety cabinets or anaerobic chambers, providing a practical foundation for downstream single-cell and clonal analyses.

bioengineering↗

bioRxiv2025

BenchHub enables an inclusive and transparent ecosystem for community-focused benchmarking in computational biology

The rapid growth of computational methods for the computational biology field highlights the critical role of benchmarking in guiding method selection. However, there is no standardised data structure that effectively links and stores datasets, performance metrics and available ground truth. Without such a unified and shareable structure, it is difficult for the community to contribute, update and extend existing benchmarking studies to ensure long-term relevancy. To address this challenge, we present BenchHub, a community-oriented ecosystem with a modular R6-based structure that enables "living benchmarking." BenchHub comprises three key components: (i) a Trio database that links datasets, performance metrics, and supporting evidence (e.g. ground truth), (ii) a BenchmarkStudy structure that captures the different benchmark study designs, and (iii) a series of tools together with vignettes and interactive platform that allow users to gain insights from the benchmarking results. Together, these components streamline the benchmarking process for benchmark study developers, methods contributors, and benchmark consumers, promoting reproducibility, comparability, and long-term sustainability in computational biology.

bioinformatics↗