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arXiv2025

Intelligent Software System for Low-Cost, Brightfield Segmentation: Algorithmic Implementation for Cytometric Auto-Analysis

Bright-field microscopy, a cost-effective solution for live-cell culture, is often the only resource available, along with standard CPUs, for many low-budget labs. The inherent challenges of bright-field images -- their noisiness, low contrast, and dynamic morphology -- coupled with a lack of GPU resources and complex software interfaces, hinder the desired research output. This article presents a novel microscopy image analysis framework designed for low-budget labs equipped with a standard CPU desktop. The Python-based program enables cytometric analysis of live, unstained cells in culture through an advanced computer vision and machine learning pipeline. Crucially, the framework operates on label-free data, requiring no manually annotated training data or training phase. It is accessible via a user-friendly, cross-platform GUI that requires no programming skills, while also providing a scripting interface for programmatic control and integration by developers. The end-to-end workflow performs semantic and instance segmentation, feature extraction, analysis, evaluation, and automated report generation. Its modular architecture supports easy maintenance and flexible integration while supporting both single-image and batch processing. Validated on several unstained cell types from the public dataset of livecells, the framework demonstrates superior accuracy and reproducibility compared to contemporary tools like Cellpose and StarDist. Its competitive segmentation speed on a CPU-based platform highlights its significant potential for basic research and clinical applications -- particularly in cell transplantation for personalised medicine and muscle regeneration therapies. The access to the application is available for reproducibility

q-bio.QM↗

arXiv2026

Geometric Reliability of Neural Population Codes: Sampling Calibration and Within-Session Nonstationarity

Trial-to-trial variability limits how reliably neural population geometry can be estimated, while comparisons across populations depend on neuron and trial counts, response quality, and clustered sampling. We quantified within-session geometric reliability using Shesha, the Spearman correlation between representational dissimilarity matrices estimated from independent trial subsets, in all 39 Steinmetz Neuropixels sessions and in olfactory bulb and piriform cortex recordings from Bolding and Franks. Steinmetz analyses matched neurons and repetitions, compared observed reliability with a stationary residual-bootstrap expectation, and used mouse-level or mouse-clustered inference. Mean matched reliability was 0.0402 across 312 area-by-session recordings. Regional differences and reliability above the stationary benchmark did not survive correction. Temporal effects received the strongest support: interleaving early and late trials increased reliability relative to blocked allocation ($Δ=0.02666$, $q=0.001953$), and RDM similarity declined with within-session lag (mean mouse-level slope $=-0.01912$, $q=0.001953$; $n=10$ mice). Outer-cross-fitted reliability was not associated with choice-direction coupling or stimulus or response-direction decoding after correction. Olfactory comparisons remained descriptive because few paired sessions and no animal identities were available. In held-out simulations, associative recurrence outperformed feedforward subspace denoising but not divisive normalization. Representational geometry became less reproducible with temporal separation within a session, and comparisons across neural populations require sampling calibration and independent inference.

q-bio.NC↗

arXiv2026

Large-scale spatial variable gene atlas for spatial transcriptomics

Spatial variable genes (SVGs) reveal critical information about tissue architecture, cellular interactions, and disease microenvironments. As spatial transcriptomics (ST) technologies proliferate, accurately identifying SVGs across diverse platforms, tissue types, and disease contexts has become both a major opportunity and a significant computational challenge. Here, we present a comprehensive benchmarking study of 20 state-of-the-art SVG detection methods using human slides from STimage-1K4M, a large-scale resource of ST data comprising 662 slides from more than 18 tissue types. We evaluate each method across a range of biologically and technically meaningful criteria, including recovery of pathologist-annotated domain-specific markers, cross-slide reproducibility, scalability to high-resolution data, and robustness to technical variation. Our results reveal marked differences in performance depending on tissue type, spatial resolution, and study design. Beyond benchmarking, we construct the first cross-tissue atlas of SVGs, enabling comparative analysis of spatial gene programs across cancer and normal tissues. We observe similarities between pairs of tissues that reflect developmental and functional relationships, such as high overlap between thymus and lymph node, and uncover spatial gene programs associated with metastasis, immune infiltration, and tissue-of-origin identity in cancer. Together, our work defines a framework for evaluating and interpreting spatial gene expression and establishes a reference resource for the ST community.

stat.AP↗

arXiv2026

Propensity Straight-Through Gradients for Discrete Stochastic Systems

Continuous-time Markov chains (CTMCs) provide the backbone for modeling discrete stochastic dynamics across applied, physical, and biological sciences. Their integration with modern gradient-based machine learning, however, is limited by the hard categorical event selection intrinsic to Gillespie-type simulation algorithms. We exploit the affine state update to obtain the exact one-step conditional-mean sensitivity by differentiating normalized reaction propensities. We pair this backward rule with exact forward trajectories to define the propensity straight-through (PST) estimator. At the trajectory level, we show that one-step sensitivities composed across events can depart from the exact multistep sensitivity. We derive the resulting per-step discrepancy in closed form and prove that it vanishes identically for affine downstream dependence. PST matches the accuracy of Gumbel-Softmax straight-through across all benchmarks: reversible dimerization (0.06% error), a genetic oscillator (1.7% error), a 50-task repressilator suite (0.17% median error), and patch-clamp ion-channel recordings ($R^2$ = 0.988). Under matched settings, PST converges 3.0-fold faster on the oscillator and 2.1-fold faster on the ion channel. At deep-learning scale, PST trains a 203,796-parameter stochastic reaction network with hard sampling, reaching 98.22% MNIST digit classification accuracy. By differentiating an exact conditional mean rather than a relaxed sample, PST offers a temperature- and Gumbel-free path to scalable gradient-based learning through exact stochastic trajectories.

q-bio.QM↗

arXiv2026

Storage-Centric System Designs for Enabling Fast, Efficient, and Low-Cost Genomic and Metagenomic Analyses

Genomic and metagenomic analyses play critical roles in many fields, such as precision medicine, urgent clinical settings, discovering early warnings of communicable diseases, ensuring food safety through pathogen monitoring, agriculture, and scientific discovery. Due to the challenges of analyzing and storing massive volumes of genomic and metagenomic sequence data, significant efforts have been made to accelerate (meta)genomic analyses and store sequence data compressed. Despite the benefits of these techniques, we identify two major outstanding problems in accessing stored sequence data and supplying it to the analysis units: (i) the data movement bottleneck due to moving large amounts of low-reuse data from storage and the unnecessary burden on the rest of the system, and (ii) the data preparation bottleneck, where compressed sequence data needs to be first decompressed and formatted before analysis. In this dissertation, we present customized storage-centric systems, which efficiently (i) analyze (meta)genomic data inside the storage system, and (ii) enable highly-compressed storage and high-performance access of large-scale sequence data, thereby alleviating the overheads of data movement, computation, and data preparation. We demonstrate that the proposed systems significantly improve system performance, energy efficiency, and system cost-efficiency of (meta)genomic analysis. We hope that the storage-centric systems proposed in this dissertation facilitate the broader adoption of (meta)genomic analyses and inspire future research to fundamentally improve the performance, energy efficiency, and cost-effectiveness of other data-intensive application domains related to health and life sciences.

cs.AR↗

arXiv2026

Importance and methods to control, vary, and characterize mud strength for studying locomotion

Animals and robots encounter mud at the water-land interface. Like sand, mud can stay solid or flow like a fluid. Unlike sand, the yield strength of mud at which solid-fluid transitions occur depends on not only the amount of solid relative to fluid (water in mud, air in dry sand), but also how much coarse grains and fine clay are within the solid. Despite understanding of locomotion on/within dry sand dominated by coarse grains with repulsive normal forces and friction, little is known for mud dominated by fine clay with strong cohesion. Here, we developed methods to prepare uniform mud of controlled, variable yield strength and characterize and track its drift from water evaporation. Compared to other flowable substrates, mud strength measured by upward force during penetration is weaker and can vary more, and mud sticks more during extraction to pull downward, making it more challenging for locomotion.

physics.bio-ph↗

arXiv2026

BIRDS: Characterizing and Understanding Biodiversity Impact of Large Language Model Serving

Large language model (LLM) serving creates environmental impacts beyond carbon and water, including ecosystem damage through biodiversity-related pathways. We present BIRDS, a framework for Biodiversity Impact of Request-Driven LLM Serving. BIRDS defines request-level functional units, quantifies operational and embodied biodiversity impact, and introduces Quality-Normalized Biodiversity Impact (QNBI) to jointly analyze ecological impact and response quality. Across diverse workloads, models, GPUs, and regions, BIRDS reveals that biodiversity impact accumulates at scale and exposes quality-aware serving tradeoffs. The code is available at https://github.com/TianyaoShi/BIRDS.

q-bio.OT↗

arXiv2026

Fusing Sequence Motifs and Pan-Genomic Features: Antimicrobial Resistance Prediction using an Explainable Lightweight 1D CNN-XGBoost Ensemble

Antimicrobial Resistance (AMR) is a rapidly escalating global health crisis. While genomic sequencing enables rapid prediction of resistance phenotypes, current computational methods have limitations. Standard machine learning models treat the genome as an unordered collection of features, ignoring the sequential context of Single Nucleotide Polymorphisms (SNPs). State-of-the-art sequence models like Transformers are often too data-hungry and computationally expensive for the moderately sized datasets that are typical in this domain. To address these challenges, we propose AMR-EnsembleNet, an ensemble framework that synergistically combines sequence-based and feature-based learning. We developed a lightweight, custom 1D Convolutional Neural Network (CNN) to efficiently learn predictive sequence motifs from high-dimensional SNP data. This sequence-aware model was ensembled with an XGBoost model, a powerful gradient boosting system adept at capturing complex, non-local feature interactions. We trained and evaluated our framework on a benchmark dataset of 809 E. coli strains, predicting resistance across four antibiotics with varying class imbalance. Our 1D CNN-XGBoost ensemble consistently achieved top-tier performance across all the antibiotics, reaching a Matthews Correlation Coefficient (MCC) of 0.926 for Ciprofloxacin (CIP) and the highest Macro F1-score of 0.691 for the challenging Gentamicin (GEN) AMR prediction. We also show that our model consistently focuses on SNPs within well-known AMR genes like fusA and parC, confirming that it learns the correct genetic signals for resistance. Our work demonstrates that our ensemble model overcomes the limitations of using either an order-agnostic or a standalone sequence model. Our codes are publicly available on GitHub at: https://github.com/Saiful185/AMR-EnsembleNet.

cs.LG↗

arXiv2026

VizIt: A multi-view framework for exploring single-cell, spatial, and genetic data online

Multi-omic studies increasingly require data to be examined from complementary biological perspectives, yet interactive exploration remains fragmented across modalities and tools. We present VizIt, an open-source framework for multi-view exploration of single-cell and spatial transcriptomic, epigenomic and genetic data. VizIt connects gene-, cell type-, condition-, spatial-, genomic region- and variant-centered views, enabling seamless navigation across biological perspectives. We demonstrate VizIt through the Parkinson's Cell Atlas, a customizable interactive multi-omic resource.

cs.IR↗

arXiv2025

Complexity of Activity Patterns in a Bio-Inspired Hopfield-Type Network in Different Topologies

Neural network models capable of storing memory have been extensively studied in computer science and computational neuroscience. The Hopfield network is a prototypical example of a model designed for associative, or content-addressable, memory and has been analyzed in many forms. Further, ideas and methods from complex network theory have been incorporated into artificial neural networks and learning, emphasizing their structural properties. Nevertheless, the temporal dynamics also play a vital role in biological neural networks, whose temporal structure is a crucial feature to examine. Biological neural networks display complex intermittency and, thus, can be studied through the lens of the temporal complexity (TC) theory. The TC approach look at the metastability of self-organized states, characterized by a power-law decay in the inter-event time distribution and in the total activity distribution or a scaling behavior in the corresponding event-driven diffusion processes. In this study, we present a temporal complexity (TC) analysis of a biologically-inspired Hopfield-type neural network model. We conducted a comparative assessment between scale-free and random network topologies, with particular emphasis on their global activation patterns. Our parametric analysis revealed comparable dynamical behaviors across both neural network architectures. Furthermore, our investigation into temporal complexity characteristics uncovered that seemingly distinct dynamical patterns exhibit similar temporal complexity behaviors. In particular, similar power-law decay in the activity distribution and similar complexity levels are observed in both topologies, but with a much reduced noise in the scale-free topology. Notably, most of the complex dynamical profiles were consistently observed in scale-free network configurations, thus confirming the crucial role of hubs in neural network dynamics.

q-bio.NC↗

arXiv2026

On a Geometry of Interbrain Networks

Effective analysis in neuroscience benefits significantly from robust conceptual frameworks. Traditional metrics of interbrain synchrony in social neuroscience typically depend on fixed, correlation-based approaches, restricting their explanatory capacity to descriptive observations. Inspired by the successful integration of geometric insights in network science, we propose leveraging discrete geometry to examine the dynamic reconfigurations in neural interactions during social exchanges. Unlike conventional synchrony approaches, our method interprets inter-brain connectivity changes through the evolving geometric structures of neural networks. This geometric framework is realized through a pipeline that identifies critical transitions in network connectivity using entropy metrics derived from curvature distributions. By doing so, we significantly enhance the capacity of hyperscanning methodologies to uncover underlying neural mechanisms in interactive social behavior.

q-bio.NC↗

arXiv2026

Memory as an Energy Landscape---Hopfield

This chapter reconstructs the Hopfield network as a physical theory of memory rather than merely an early neural-network algorithm. It begins with the problem as it stood before 1982-threshold logic, Hebbian association, correlation memories, and recurrent binary networks-and isolates what Hopfield's synthesis added: a dynamical definition of content-addressable memory, a symmetric recurrent architecture with a Lyapunov function, a Hebbian embedding of patterns in its couplings, and a physical account of basins, robustness, and graceful degradation. The binary and graded-response energy functions are derived in full, together with the signal-crosstalk decomposition governing pattern stability, the mean-field theory of retrieval at extensive load, and the zero-temperature retrieval spinodal at (alpha 0.138) established by Amit, Gutfreund, and Sompolinsky. The energy-based program is then followed through analog optimization networks, polynomial dense associative memories, exponential interactions, and modern continuous Hopfield updates, including the precise conditions under which the update becomes scaled dot-product attention. Throughout, capacity claims are tied to their disorder ensemble, scaling limit, and success criterion, showing why numerically different storage limits need not conflict. A closing assessment distinguishes established results from surviving principles, assumption-bound limitations, and open problems, treating the Hopfield network as an effective theory whose symmetry, locality, and point-neuron assumptions delimit its biological reach. Fixed-seed numerical experiments expose the mechanisms discussed but do not substitute for analytical results.

cs.NE↗

arXiv2026

Agentic BAIM-LLM Evaluation (ABLE): Benchmarking LLM Use of Protein Design Tools

We introduce ABLE, a benchmark for evaluating LLM agents' ability to use biological AI models (BAIMs), such as ProteinMPNN and AlphaFold3, in dual-use protein design workflows. ABLE assesses agent performance through a set of tasks spanning structure retrieval, sequence generation, and design validation. We evaluate 15 frontier models and find that seven refuse all tasks, while the remaining models exhibit substantial performance differences. Claude Sonnet 4 and Gemini 3 Pro achieve the highest scores across information retrieval, tool selection, and tool use. We further compare model performance on a subset of tasks against an expert human baseline. Our results suggest that current LLMs can substantially lower barriers to protein design, but remain inconsistent in planning, strategy generation, and integrating biological knowledge with tool use.

cs.AI↗

arXiv2026

OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

Health digital twins (HDTs) promise patient-specific modeling and decision support but current approaches remain structurally fragmented: monolithic models that address a single organ or task lack cross-scale fidelity, while system-level twins lack generalizable architectural frameworks. We propose OmniBioTwin, a System-of-Twinned-Systems (SoTS) framework that organizes HDTs as modular computational entities coupled through explicit interaction operators within a multi-layer network architecture. The framework comprises seven coordinated layers - spanning data integration, autonomous twin modeling, cross-scale coupling, temporal synchronization, and human-in-the-loop decision support. We demonstrate OmniBioTwin by instantiating a multiscale twin for glucagon-like peptide-1 (GLP-1) signaling pathways in Alzheimer's disease, illustrating how molecular, cellular, and organ-level twins can be composed and coupled within a unified system.

q-bio.QM↗

arXiv2026

Inferring Affective Consciousness in an Artificial Agent: A Case Study

Creatures that display 'hedonic place preference behaviour' are thought by many scientists to experience feelings, on the assumption that their attraction to pleasure-producing substances which lack nutritional value (e.g. cocaine, morphine) cannot easily be attributed to unconscious instinctual behaviour. In this paper, we discuss how a simple artificial agent that instantiates attributes of an affective system engaging in felt uncertainty about its intrinsic needs in relation to environmental resources can similarly display hedonic place preference behaviour -- through an apparently subjective form of information processing -- while simultaneously being entirely deter-ministic. We outline some implications of this artificially engineered behaviour for our understanding of the physical basis of consciousness and the experience of free will.

cs.AI↗

arXiv2026

Stable Coexistence in Ecologies and Games

We study feasible stable equilibria of Lotka-Volterra systems and their higher-order extensions. We complete the classification of impossible ecological interaction networks with at most four species and extend several of these impossibility results to families with arbitrarily many species. We then show that these sign-pattern obstructions are specific to the pairwise Lotka-Volterra model: arbitrary prescribed growth rates and pairwise coefficients can be supplemented by higher-order interactions so as to admit a feasible asymptotically stable equilibrium. Through the correspondence with replicator dynamics, we interpret feasible equilibria of higher-order Lotka-Volterra systems as totally mixed symmetric Nash equilibria of symmetric multiplayer games, derive bounds on their number, and study their robustness under perturbations of the payoff tensors. We conclude by showing that every impossible ecology determines a nonempty open class of symmetric two-player games with no totally mixed evolutionarily stable strategy.

math.DS↗

arXiv2026

Structural Hierarchy and Geometry in Molecular Representation Learning

Molecular self-supervised learning uses chemical structures to guide which molecular embeddings should be similar. We study whether explicitly encoding a molecule's Bemis-Murcko scaffold and using it to supervise the molecular embedding changes what the model learns. We further test whether this effect depends on the embedding geometry by comparing Euclidean and Lorentz contrastive objectives. Across two augmentation strengths, scaffold-supervised models consistently organize molecules according to both identical and structurally related scaffolds. The resulting embeddings also improve molecular property prediction on several tasks, while the exact gains depend on the predicted property. The effect of scaffold supervision on molecular organization is stronger under Lorentz objectives, but neither geometry provides a consistent overall advantage. These results show that explicitly teaching the relation between a molecule and its structural core can reliably shape the organization of molecular embedding space, while the extent of usefulness of this organization remains task dependent.

cs.LG↗

arXiv2026

Rate-Coding Bundle Memory: A Unified Model of Memory and Control for Symbolic Computation in the Brain

We propose a neurobiologically plausible model of cognition that combines the advantages of connectionist and symbolic systems, and that can explain a wide range of cognitive phenomena. This model, called Rate-Coding Bundle Memory (RCBM), is based on the Symbolic Subsystem Hypothesis, which posits that the brain implements a symbolic subsystem within its fundamentally connectionist nature. RCBM is a hybrid model that uses rate coding to represent symbols in a continuous space, and it uses a bundle memory system to store and retrieve these symbols. The model is capable of solving a wide range of cognitive phenomena, including one-shot learning, pattern separation, and the binding problem. We argue that RCBM provides a promising framework for understanding the nature of cognition, and that it can be used to develop more sophisticated models of cognition in the future.

q-bio.NC↗