Biology subjects

Yang, R.

Publications and source records attributed to Yang, R..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

AAV-based temporal APOE4-to-APOE2 replacement reveals rebound adaptation and RAB24-mediated Aβ and cholesterol dysregulation

APOE-targeted gene therapy offers a promising strategy for modifying Alzheimers disease (AD) risk, yet the temporal dynamics and context-dependent effects of APOE isoform modulation remain poorly defined. Here, we developed a rapid AAV-based platform enabling inducible in vivo replacement of APOE4 with APOE2. In 5xFAD mice, sustained APOE4 expression exacerbated cognitive decline, A{beta} deposition (parenchymal and vascular), and glial activation, whereas long-term APOE2 expression--with concurrent APOE4 silencing--significantly reversed these pathological features and rescued cognitive function. In contrast, short-term APOE2 replacement conferred no benefit and unexpectedly worsened behavioral and pathological outcomes. Transcriptomic profiling revealed that APOE4-associated gene signatures were broadly reversed by long-term APOE2 expression, but paradoxically aggravated by short-term replacement. Among these, RAB24--a regulator of autophagic trafficking--was upregulated by APOE4 and short-term APOE2 but suppressed by long-term APOE2. RAB24 elevation impaired A{beta} clearance and cholesterol homeostasis via lysosomal retention in primary astrocytes and neurons. Together, these findings uncover a rebound-adaptation mechanism that shapes APOE2 therapeutic outcomes, identify RAB24 as a modifiable node in A{beta} and cholesterol metabolism, and establish a temporally controlled gene therapy platform to inform the design of future APOE-targeted interventions in AD.

neuroscience↗

bioRxiv2025

Microbial Tryptophan Metabolism Activates Host Lysosomal Activity to Facilitate Lipid Breakdown and Ameliorate Hepatic Steatosis

Lysosomes are central to lipid metabolism, yet how gut microbiota-derived metabolites regulate lysosomal function to influence host lipid homeostasis remains unknown. Here, we identify an evolutionarily conserved mechanism in which bacterial tryptophan metabolism activates lysosomal activity to promote lipid breakdown. By developing a lysosomal-responsive lipid reporter in C. elegans to screen for bacterial metabolic states that modulate host lipid storage, we discover that E. coli tryptophan catabolism via tryptophanase TnaA induces lysosomal lipid chaperone LBP-8, driving lipid mobilization. Moreover, tryptophan metabolites enhanced lysosomal acidification and degradation capacity, while genetic disruption of lysosomal regulators reversed these effects. Strikingly, bacterial tryptophan metabolism further promoted mitochondrial {beta}-oxidation through lysosomal lipase activity. This pathway was conserved in mammalian hepatocytes, where E. coli-derived tryptophan metabolites enhance lysosomal function and reduce lipid accumulation. In high-fat diet mice, restoring gut bacterial tryptophan metabolism alleviated hepatic steatosis. Our work uncovers microbiota-regulated lysosomal activation as a critical axis in lipid homeostasis, highlighting its potential as a therapeutic target for metabolic disorders linked to lysosomal dysfunction. SignificanceWe uncover a conserved mechanism by which microbial tryptophan metabolism enhances lysosomal function to maintain host lipid homeostasis. Specifically, we demonstrate that bacterial tryptophan catabolism--via the enzyme TnaA--promotes lysosomal acidification, proteolytic capacity, and structural remodeling in C. elegans, driving lipid breakdown through the lysosomal chaperone LBP-8. This activation boosts mitochondrial {beta}-oxidation and reduces lipid storage. Importantly, the same pathway operates in mammalian hepatocytes and in a high-fat diet mouse model, where restoring bacterial tryptophan metabolism markedly alleviates hepatic steatosis. Our findings bridge microbial metabolism and lysosomal dynamics, offering fresh insights into host-microbe crosstalk and metabolic regulation. HighlightsTnaA-mediated bacterial tryptophan catabolism promotes lipid mobilization via lysosomal chaperone. Bacterial tryptophan metabolites boost lysosomal function, lipid breakdown, and mitochondrial {beta}-oxidation. Conserved microbiota-lysosome-lipid axis from worms to mammalian liver. Restoring gut bacterial tryptophan metabolism alleviates hepatic steatosis in high-fat diet mice.

cell biology↗

bioRxiv2025

Comparing phenotypic manifolds with Kompot: Detecting differential abundance and gene expression at single-cell resolution

Single-cell studies are frequently designed to compare across conditions such as health and disease. However, existing computational approaches typically rely on grouping cells into discrete populations before making comparisons, which can limit resolution for detecting state-dependent changes. Here, we introduce Kompot, a statistical framework for comparative analysis of multi-condition single-cell data. Kompot quantifies both differential abundance, capturing how cells redistribute across the phenotypic space, and differential expression, identifying condition-specific transcriptional changes that may be localized, heterogeneous, or oppositely regulated across states. By modeling cell density and gene expression as continuous functions over a shared cell-state representation, Kompot enables single-cell resolution inference with principled uncertainty estimates, without requiring predefined clusters or cell types. Applying Kompot to aging murine bone marrow, we identified a continuum of shifts in hematopoietic stem cell and mature cell states, transcriptional remodeling of monocytes independent of compositional changes, and divergent regulation of oxidative stress response genes across cell types. We demonstrate the utility of Kompot in disease settings by identifying cell-state and gene expression changes associated with improved efficacy of combinatorial immunotherapy in melanoma. Additionally, Kompot enables multi-sample comparative analysis by accounting for sample-to-sample heterogeneity. By capturing both global and cell-state-specific effects of perturbation, the Kompot framework is broadly applicable to dissecting condition-specific effects in complex single-cell landscapes.

bioinformatics↗

bioRxiv2025

LSH-mediated resolution of R-loops mitigates transcription-replication conflicts to preserve genomic stability in prostate cancer cells

Prostate cancer cells exhibit heightened transcriptional activity to sustain their aggressive phenotype, yet this creates DNA topological stress, leading to RNA: DNA hybrids (R-loops) and DNA damage that compromise genomic stability. LSH, an SNF2-family chromatin remodeler, is frequently dysregulated in cancers and linked to tumor progression, but its mechanistic role in genome maintenance remains unclear. Here, we demonstrate that LSH resolves R-loops in an ATP-dependent manner, mitigating transcription- replication (TR) conflicts in prostate cancer cells. LSH depletion caused R- loop accumulation due to reduced FANCD2 recruitment, exacerbating DNA damage and impairing Rad51 filament formation. Strikingly, LSH deficiency also increased R-loops at promoters of MYC and E2F target genes, stalling RNA polymerase II elongation and disrupting transcriptional programs critical for proliferation. Our findings reveal LSH is a key guardian of genome integrity, resolving R-loops to prevent TR conflicts and maintaining DNA repair fidelity. By linking LSH to R-loop resolution and transcriptional regulation, this study reveals its dual role in prostate cancer pathogenesis-- supporting malignant proliferation while safeguarding genomic stability. These insights nominate LSH as a potential therapeutic target to disrupt oncogenic transcription and induce synthetic lethality in prostate cancer.

cancer biology↗

bioRxiv2025

Development of a CRISPR/Cas9-induced gene editing system for Pseudoalteromona fuliginea and its applications in functional genomics

Pseudoalteromonas has been used as a model system to study cold adaptation and is of widespread interest in biotechnology and ecology. To explore its physiological responses to extreme cold, uncover functional genes, and clarify their ecological roles, efficient genetic tools are essential. However, existing genetic manipulation methods in Pseudoalteromonas rely on traditional homology-based recombination, which is inefficient and time-consuming. Consequently, improving editing efficiency is crucial for advancing both basic research and applied potential. Here, we introduced the CRISPR/Cas9 system into Pseudoalteromonas for the first time, and conducted an extensive investigation into the application of the Type II CRISPR/Cas9 system for gene editing in Pseudoalteromonas fuliginea, a representative species thriving in the frigid polar oceans. To validate the feasibility of the CRISPR/Cas system in P. fuliginea, multiple genes were selected as targets and confirmed the gene editing effects through phenotypic changes or gene expression. We have successfully achieved both gene knockouts and insertions in P. fuliginea, encompassing the deletion of genes such as fliJ, indA, and genes encoding Pf sRNAs, as well as the in vivo insertion of 3xflag and the gfp gene. The average CRISPR/Cas9 gene editing efficiency in P. fuliginea exceeded 70% (range: 73.3%-95.8%), which is significantly higher than the traditional homology-based approach (less than 0.1%). In summary, we developed an efficient CRISPR/Cas9-based editing system in P. fuliginea, which can be utilized to accelerate the development of Pseudoalteromonas as a model system for addressing fundamental questions related to extreme environmental adaptation and to fulfill its potential biotechnological applications. IMPORTANCEPseudoalteromonas fuliginea is a marine bacterium with great potential for ecological and biotechnological research, yet its genetic manipulation has long been a technical challenge. In this study, we developed a gene editing system based on CRISPR technology that enables efficient and precise genome modification in this organism. Using this system, we successfully deleted, inserted, and tagged multiple genes, including regulatory and non-coding elements, with high success rates. Notably, several of these genes are linked to key traits such as motility and stress response, which contribute to microbial adaptation in polar environments. This tool allows researchers to directly test gene function and study microbial adaptation in cold marine environments. The ability to perform reliable genetic edits in Pseudoalteromonas fuliginea opens new possibilities for its use as a model organism and will support future advances in microbial ecology, environmental microbiology, and marine biotechnology.

molecular biology↗

bioRxiv2025

Dual Metabolic Blockade by Metformin and Dichloroacetate Induces Lethal Energy Crisis in Chemoresistant NSCLC

Acquired chemoresistance, often linked to metabolic adaptation, severely limits therapeutic efficacy in non-small cell lung cancer (NSCLC). Strategies targeting resistance-associated metabolic plasticity are urgently needed. Here, we investigated the combination of Metformin (mitochondrial Complex I inhibitor) and Dichloroacetate (DCA; PDK inhibitor) in chemo-sensitive human A549 NSCLC cells and an acquired Doxorubicin-resistant subline (A549-DR). A549-DR cells displayed significant Doxorubicin resistance ([~]15.6-fold; IC50: 3.9 {micro}M vs 0.25 {micro}M in parental A549) and exhibited enhanced glycolysis (higher ECAR) while retaining substantial oxidative phosphorylation (OxPhos) capacity. While single-agent Metformin or DCA showed limited cytotoxicity, their combination induced potent synergistic cell death (Combination Index < 0.5) specifically in A549-DR cells compared to parental A549 (CI [~] 0.8-1.1). Mechanistically, Metformin inhibited OxPhos, while DCA promoted pyruvate entry into the TCA cycle, preventing compensatory glycolysis. This dual blockade precipitated a catastrophic metabolic collapse uniquely in A549-DR cells, marked by simultaneous suppression of OxPhos (OCR) and glycolysis (ECAR), leading to severe ATP depletion ([~]85% reduction), hyperactivation of the energy sensor AMPK, and robust induction of apoptosis ([~]58% Annexin V positive). Parental A549 cells were less susceptible, experiencing moderate metabolic inhibition and apoptosis ([~]32% Annexin V positive). Our findings highlight a powerful synergistic strategy that exploits the acquired metabolic vulnerabilities of chemoresistant NSCLC cells, inducing an irrecoverable energy crisis and offering a promising therapeutic approach to counteract treatment failure.

immunology↗

bioRxiv2025

Synergistic Effect of Thermoneutral Housing and Chronotherapeutic PD-1 Blockade Overcomes Melanoma Resistance

BackgroundImmune-checkpoint blockade transformed melanoma therapy, yet the B16-F10 model resists PD-1 inhibition. Sub-thermoneutral housing (22{degrees}C) causes cold stress, and dosing outside circadian immune peaks dampens anti-tumour immunity. We hypothesised eliminating both would render B16-F10 curable. MethodsC57BL/6 mice (n=40) with B16-F10 tumours were randomised to conventional (22{degrees}C; ZT22 PD-1 timing), chronotherapy only (22{degrees}C; ZT4), thermoneutrality only (30{degrees}C; ZT22), or "double-hit" (30{degrees}C; ZT4). Anti-PD-1 was given on days 3, 6, 9, 12. Tumour volume, weight, survival, and day-14 serum IFN-{gamma} were recorded. Synergy threshold {Delta} [≥] 20% was prespecified. ResultsDay 14 control tumours were 1207{+/-}48 mm3. Chronotherapy and thermoneutrality slowed growth (737{+/-}55 mm3 and 565{+/-}28 mm3 respectively; p<0.0001). The double-hit nearly halted progression (43{+/-}12 mm3, -96%; p<10{square}1{square}), yielding seven complete responses and 100% survival. IFN-{gamma} increased 8.8-fold versus control (430{+/-}24 vs 48{+/-}7 pg mL{square}1; p<10{square}1{square}). Bliss {Delta} was 25%, confirming synergy. ConclusionsRemoving cold stress and circadian mistiming unmasks curative PD-1 response in refractory melanoma. Available warming blankets and morning infusions suggest a practical tactic to rescue PD-1 efficacy in "cold" tumours. A factorial multicentre trial is warranted.

cancer biology↗

bioRxiv2025

Supra-resonant wingbeats in insects

Powering small-scale flapping flight is challenging, yet insects sustain exceptionally fast wingbeats with ease. Since insects act as tiny biomechanical resonators, tuning their wingbeat frequency to the resonant frequency of their springy thorax and wings could make them more efficient fliers. But operating at resonance poses control problems and potentially constrains wingbeat frequencies within and across species. Resonance may be particularly limiting for the many orders of insects that power flight with specialized muscles that activate in response to mechanical stretch. Here, we test whether insects operate at their resonant frequency. First, we extensively characterize bumblebees and find that they surprisingly flap well above their resonant frequency via interactions between stretch-activation and mechanical resonance. Modeling and robophysical experiments then show that resonance is actually a lower bound for rapid wingbeats in most insects because muscles only pull, not push. Supra-resonance emerges as a general principle of high-frequency flight across five orders of insects from moths to flies.

zoology↗

bioRxiv2025

Differential Regulation of Hepatic Macrophage Fate by Chi3l1 in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) progression involves the replacement of protective embryo-derived Kupffer cells (KCs) by inflammatory monocyte-derived macrophages (MoMFs), yet the regulatory mechanisms remain unclear. Here, we identify chitinase 3-like 1 (Chi3l1/YKL-40) as a critical metabolic regulator of hepatic macrophage fate. We observed high expression of Chi3l1 in both KCs and MoMFs during MASLD development. Genetic deletion of Chi3l1 specifically in KCs significantly exacerbated MASLD severity and metabolic dysfunction, whereas MoMF-specific Chi3l1 deletion showed minimal metabolic effects. Mechanistic studies revealed that this cell type-specific regulation arises from differential metabolic requirements: KCs display elevated glucose metabolism compared to MoMFs. Chi3l1 directly interacts with glucose to inhibit its cellular uptake, thereby selectively protecting glucose-dependent KCs from metabolic stress-induced cell death while having negligible effects on less glucose-dependent MoMFs. These findings uncover a novel Chi3l1-mediated metabolic checkpoint that preferentially maintains KCs populations through glucose metabolism modulation, providing important new insights into the pathogenesis of MASLD and potential therapeutic strategies targeting macrophage-specific metabolic pathways.

molecular biology↗

bioRxiv2025

Deciphering Biosynthetic Gene Clusters with a Context-aware Protein Language Model

Microbial secondary metabolites, synthesized by biosynthetic gene clusters (BGCs), offer vast potential for biotechnological applications. Among BGC profiling techniques, computational detection methods face challenges, including time-consuming alignment and reliance on predefined profiles. To address these, we present BGC-Finder, an end-to-end pipeline utilizing protein language models for BGC detection and annotation from microbial genomes and metagenomes. This approach achieves remarkable increase in profiling speed of up to 100-fold, and employs genomic context-aware modeling to facilitate interpretable genetic essentiality assessment and large-scale BGC clustering. BGC-Finder outperformed traditional methods, successfully detecting 9.49% more biosynthetic-core genes and 27.70% more cytochrome P450s in 742 experimentally-validated BGCs. Notably, it retrieved 31 remote biosynthetic homologs from 210 polar marine metagenomes and identified 4,585 BGCs with 6,388 core genes from 256 fungal genomes. These findings highlight BGC-Finders capability to illuminate "microbial biosynthesis dark matter" (sequence-unrelated, function-similar biosynthetic enzymes) and expedite natural product discovery. HighlightsO_LIBGC-Finder is an accurate and ultrafast pipeline leveraging protein language models (pLMs) to predict and annotate biosynthetic gene clusters (BGCs) from microbial genomes and metagenomes. C_LIO_LIThe genomic context-aware model enables interpretable analysis: attention-driven identification of essential biosynthetic genes and embedding-guided BGC clustering. C_LIO_LIBGC-Finder sensitively retrieves remote homologous BGCs from both bacteria and fungi genomes, uncovering hidden microbial biosynthesis dark matter. C_LIO_LIWe discovered a non-ribosomal peptide synthetase (NRPS) family, which involved into function-specific BGCs in two evolutionarily distant fungi. C_LI

bioinformatics↗

bioRxiv2025

Immune Niche Formation in Engineered Mouse Models Reveals Mechanisms of Tumor Dormancy

Residual tumor cells can persist in a dormant state during clinical remissions that may last decades. The mechanisms that lead to such growth control vs. eventual reactivation and macroscopic tumor outgrowth remain unclear. Here, we report data from a mouse model that reveals a key role of host immunity and the cellular and molecular mechanisms that control tumor dormancy. Abrogation of myeloid-specific TGF-{beta}RII expression (T{beta}RIImyeKO) resulted in an IFN-{gamma} rich immune microenvironment. IFN-{gamma} in turn elevated KLF4-mediated SLURP1 production in malignant cells, which is critical to the tumor cell quiescent state through interruption of fibronectin-integrin signaling pathways. The dormant tumor lesions were located in spatially localized immune niches rich in NK cells, cDCs, monocytes, and neutrophils, concomitant with tumor cell inactivation of NK cell immune surveillance through a CD200-CD200R1 mechanism. Our studies identify the IFN-{gamma}-KLF4-SLURP1 and CD200-CD200R1 axes as critical molecular drivers in tumor dormancy regulated by immune-tumor crosstalk. These insights provide enhanced mechanistic understanding of tumor dormancy in a mouse model suitable for further investigation of cancer treatment resistance and prevention of metastatic spread.

cancer biology↗

bioRxiv2025

The Physiological Component of the BOLD Signal: Impact of Age and Heart Rate Variability Biofeedback Training

Aging is associated with declines in autonomic nervous system (ANS) function, including reduced heart rate variability (HRV), impaired neurovascular coupling, and diminished cerebrovascular responsiveness--factors that may contribute to cognitive decline and neurodegenerative diseases. Understanding how aging alters physiological signal integration in the brain is crucial for identifying potential interventions to promote brain health. This study examines age-related differences in how cardiac and respiratory fluctuations influence the blood oxygenation level-dependent (BOLD) signal, using two independent resting-state fMRI datasets with concurrent physiological recordings from younger and older adults. Our findings reveal significant age-related reductions in the percent variance of the BOLD signal explained by heart rate (HR), respiratory variation (RV), and end-tidal CO2, particularly in regions involved in autonomic regulation, including the orbitofrontal cortex, anterior cingulate cortex, insula, basal ganglia, and white matter. Cross-correlation analysis also revealed that younger adults exhibited stronger HR-BOLD coupling in white matter, as well as a more rapid BOLD response to RV and CO2 in gray matter. Additionally, we investigated the effects of heart rate variability biofeedback (HRV-BF) training, a non-invasive intervention designed to modulate heart rate oscillations. The intervention altered physiological-BOLD coupling in an age- and training-dependent manner: older adults who underwent HRV-BF to enhance HR oscillations exhibited a shift toward younger-like HR-BOLD coupling patterns, while younger adults who trained to suppress HR oscillations showed increased CO2-BOLD coupling. These findings suggest that HRV-BF may help mitigate age-related declines in autonomic or cerebrovascular function. Overall, this study underscores the role of physiological dynamics in brain aging and highlights the importance of considering autonomic function when interpreting BOLD signals. By demonstrating that HRV-BF can modulate physiological-BOLD interactions, our findings suggest a potential pathway for enhancing cerebrovascular function and preserving brain health across the lifespan.

neuroscience↗

bioRxiv2025

OctopusV and TentacleSV: a one-stop toolkit for multi-sample, cross-platform structural variant comparison and analysis

Structural variants (SVs) significantly influence genomic variability and disease, but their accurate analysis across multiple samples and sequencing platforms remains challenging. We developed OctopusV, a tool that standardizes ambiguous breakend (BND) annotations into canonical SV types (inversions, duplications, translocations) and integrates variant calls using flexible set operations, such as union, intersection, difference, and complement, enabling cohort-specific variant identification. Together with TentacleSV, an automated pipeline, OctopusV provides an end-to-end solution from raw data to final callsets. Evaluations show improved precision, recall, and consistency, highlighting its value in cancer genomics and rare disease diagnostics. Both tools are available at https://github.com/ylab-hi/OctopusV and https://github.com/ylab-hi/TentacleSV.

bioinformatics↗

bioRxiv2025

Cocktail Chemical Labeling for In-Depth Surfaceome Profiling of Bone-Marrow Derived Dendritic Cells

Cell surface proteins (CSPs) are crucial identifiers for cell types and states, especially in dendritic cells (DCs). Current proteomic methods for profiling CSPs are limited by their hydrophobic nature and low abundance, which often require genetic or cell surface engineering and exhibit biased and insufficient labeling efficiency. Herein, we report [Ru(bpy)3]Cl2 (Ru) for effective biotinylation on the cell surfaceome via a simple "mix and lighten" method. The versatile photoredox pathways of Ru are leveraged using a probe cocktail of biotin-phenol and biotin-hydrazide for improved substrate coverage. The "cocktail" labeling strategy results in reproducible identification of up to 733 plasma membrane proteins on HeLa cells, and is further applied to map dynamic changes in the surfaceome during the differentiation of primary bone marrow-derived dendritic cells, which demonstrates a user-friendly and deep-surfaceome-coverage tool for profiling dynamic changes in primary cells, with potential implications for cell identities, functional states, and novel drug targets.

cell biology↗

bioRxiv2025

Harnessing Neutrophils to Deliver Antibiotics Non-Invasively across the Tympanic Membrane for Otitis Media Treatment

Acute otitis media (AOM) is a leading cause of pediatric antibiotic prescriptions. Systemic antibiotics cause side effects and antibiotic resistance, whereas local delivery of antibiotics (directly to the middle ear) is hindered by an impermeable biological barrier, the tympanic membrane (TM). Here, we report on a liposome that hitchhikes on neutrophils to deliver antibiotics to the site of infection. Distinct from previous immune-cell-based therapies, we enable neutrophil hitchhiking via a topical application of hydroxylated liposomes, thus bypassing the invasive neutrophil harvesting procedures. The hydroxylated liposomes are opsonized by the complement protein fragments and subsequently internalized by native neutrophils. A simple topical application completely cures AOM in an established chinchilla model. It points to a low-cost and non-invasive treatment for this prevalent disease, poised to reduce pediatric antibiotic usage.

bioengineering↗

bioRxiv2025

Macrogenetic atlas of prokaryotes

Macrogenetics investigates patterns and predictors of intraspecific genetic variation across diverse taxa, offering a framework for understanding species diversity and addressing evolutionary hypotheses. Here, we present a macrogenetic atlas of prokaryotes (MAP), integrating genomic data from 15,235 prokaryotic species (30 parameters in 12 categories) and population genetic data from 786 species (22 parameters in 7 categories), together with phylogenetic, phenotypic, and ecological information. MAP enables quantitative species characterization, straightforward cross-species comparisons, and easy generation, testing, and refinement of evolutionary hypotheses. For example, our analyses show that long- and short-range genetic linkage capture distinct evolutionary dynamics and independently shape genetic diversity. Further, we propose that as within-species diversity increases, epistatic selection increasingly contributes to shaping genetic diversity, exemplified by convergent selection-driven structures (ecospecies) identified in Streptococcus mitis and S. oralis. Overall, MAP represents a widely applicable resource (www.genomap.cn) and offers novel insights into the drivers of macroevolution and the life cycle of prokaryotic species.

microbiology↗

bioRxiv2025

A Comprehensive Benchmark of Tools for Efficient Genomic Interval Querying

Efficiently querying genomic intervals is fundamental to modern bioinformatics, enabling researchers to extract and analyze specific regions from large genomic datasets. While various tools have been developed for this purpose, there lacks a comprehensive comparison of their performance, memory usage, and practical utility. We present a systematic evaluation of genomic interval query tools using simulated datasets of varying sizes. Our benchmarking framework, segmeter, assesses both basic and complex interval queries, examining runtime performance, memory efficiency, and query precision across different tools and data structures. This comprehensive analysis provides insights into the strengths and limitations of different approaches to genomic interval querying, offering guidance for tool selection based on specific use cases and data requirements. The segmeter framework and all benchmark data are freely available, facilitating reproducibility and enabling researchers to conduct their own comparative analyses.

bioinformatics↗

bioRxiv2025

Field-Programmable Gate Array Based Ultra-Low Power Discrete Fourier Transforms for Closed-Loop Neural Sensing

Digital implementations of discrete Fourier transforms (DFT) are a mainstay in feature assessment of recorded biopotentials, particularly in the quantification of biomarkers of neurological disease state for adaptive deep brain stimulation. Fast Fourier transform (FFT) algorithms and architectures present a substantial power demand from onboard batteries in implantable medical devices, necessitating the development of ultra-low power Fourier transform methods in resource-constrained environments. Numerous FFT architectures aim to optimize power and resource demand through computational efficiency; however, prioritizing the reduction of logic complexity at the cost of additional computations can be equally or more effective. This paper introduces a minimal-architecture single-delay feedback discrete Fourier transform (mSDF-DFT) for use in ultra-low-power field programmable gate array applications and shows energy and power improvements over state-of-the-art low-power DFT and FFT methods. In a neural sensing application, we observe a 33% reduction in dynamic power and 4% reduction in resource utilization when compared to state-of-the-art FFT algorithms; 38% reduction in dynamic power and 4% reduction in resource utilization when compared to Goertzel Algorithm. While designed for use in closed-loop deep brain stimulation and medical device implementations, the mSDF-DFT is also easily extendable to any ultra-low-power embedded application.

neuroscience↗