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202 recordsLinked to original sources

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

Agentic AI uncovers conserved cross-tissue protein co-abundance programs inaccessible to single-dataset analysis

Protein co-abundance clusters preserved across tissues can reveal shared disease mechanisms and candidate therapeutic targets, particularly when proteins implicated in organ-confined diseases converge in peripheral or accessible tissues. However, previous cross-tissue studies have focused on biologically pre-selected tissue pairs, leaving most possible combinations and non-obvious relationships unexplored. We present an LLM-agent framework for large-scale, evidence-grounded comparison of tissue-specific protein co-abundance networks. The framework constructs tissue networks, derives pairwise consensus clusters, and integrates evidence from expression atlases, protein interaction and complex databases, pathway annotations, disease catalogues, and literature. Applied to all 820 pairwise combinations of 41 human tissues and fluids, it identified 1,833 conserved co-abundance clusters across 406 tissue pairs. Colon, synovial fluid, blood, cerebrospinal fluid, and bone marrow were the most broadly connected tissues, while the most cluster-rich pairs were dominated by bone marrow. The analysis also highlighted non-obvious relationships: skin-bone marrow exceeded the anatomically adjacent bone-bone marrow pair, while colon-breast contained cancer-relevant clusters involving extracellular-matrix remodeling, lipid metabolism, and immune modulation. Cluster-level analyses generated further mechanistic hypotheses, including a brain-gut extracellular-vesicle/redox/serotonin-cofactor axis and a liver-bone marrow stress-response axis involving genes linked to white matter disease. These results provide a global, comparable landscape of conserved protein co-abundance and a hypothesis-generating resource for mechanistic and therapeutic exploration. Code and data are available at https://github.com/Gry1005/AgenticAI-conserved-cross-tissue-protein-co-abundance.

cs.AI↗

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

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↗

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

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↗

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

A Unary-to-Nonunary Transition in the Accepting-State Spectrum of Right Quotient for Permutation Automata

This paper resolves the open larger-alphabet quotient case in the accepting-state complexity theory of permutation automata. Rauch and Holzer showed that, in the unary setting, the attainable right-quotient accepting-state complexities are exactly $[1,mn]$. We prove that over arbitrary alphabets the exact spectrum is $g^{\operatorname{asc}}_{-1,\mathrm{PFA}}(m,n)=\{0\}$ if $m=0$ or $n=0$, and $g^{\operatorname{asc}}_{-1,\mathrm{PFA}}(m,n)=\mathbb{N}_{>0}$ if $m,n\ge 1$. Thus, once both input languages are nonempty, every positive accepting-state complexity is attainable for right quotient, and $0$ is the only unavoidable magic value. The proof has two parts. First, we show that if $m,n\ge 1$, then the quotient language $KL^{-1}$ cannot be empty when $K$ and $L$ are accepted by permutation automata with $\operatorname{asc}(K)=m$ and $\operatorname{asc}(L)=n$; this follows from the bijectivity of the transition action. Second, for every $m,n\ge 1$ and every $α\ge m$, we construct a ternary witness pair $(A^{\mathrm{q}}_{m,α},B^{\mathrm{q}}_{n,α})$ such that $\operatorname{asc}(L(A^{\mathrm{q}}_{m,α}))=m$, $\operatorname{asc}(L(B^{\mathrm{q}}_{n,α}))=n$, and $\operatorname{asc}(L(A^{\mathrm{q}}_{m,α})L(B^{\mathrm{q}}_{n,α})^{-1})=α$. The high-range construction is group-theoretic: the words accepted by $B^{\mathrm{q}}_{n,α}$ induce exactly a point stabilizer in a symmetric group, and the standard quotient construction then saturates the original final set of $A^{\mathrm{q}}_{m,α}$ to a full orbit, yielding a minimal quotient automaton with exactly $α$ final states. Combined with the known unary interval $[1,mn]$, this yields the complete spectrum and resolves the larger-alphabet right-quotient case for permutation automata.

cs.FL↗

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

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↗

arXiv2026

Mudskippers use tail thrusting to help crutching to move on mud of various wetness

At the water-land interface, amphibious fishes encounter wet flowable substrates made of granular solid-water mixtures, which can stay solid or flow like a fluid. As these substrates become wetter or drier, their yield strength (at which solid-fluid transition occurs) and cohesion (how sticky they are) both change, challenging locomotion. Despite substantial understanding of tetrapod locomotion on flowable substrates (mostly dry sand), we know little about how amphibious fishes cope with wet flowable substrates of various wetness. Here, we studied mudskippers on clay mud of controlled, variable wetness over the range where solid-fluid transition occurs. As mud became wetter, its strength decreased by 100-fold, leading the animal to sink deeper, with larger areas of body and fins contacting mud. By contrast, mud stuck most easily at intermediate wetness. The increased sinkage and contact and stickiness change caused more mud to stick to and pull against the animal on wetter mud. We also tested dry mud, which stuck to animal fins as its mucus dried. Despite these challenges, the mudskipper predominately used a conserved crutching gait on all except the wettest mud tested, with a modest performance reduction. When normal crutching became less effective, the animal assisted it with tail thrusting, by bending and straightening it to push downward and backward to generate additional thrust and lift, or even thrusting the tail to jump. These observations suggest that mudskipper's crutching motor program is well adapted to its native muddy substrates but inflexible, with most novelty in tail use.

physics.bio-ph↗

arXiv2026

JUMP-lite: Compact, reproducible benchmarking of cell representations

Image-based profiling captures rich phenotypic signatures for drug discovery and functional genomics. Large public datasets like JUMP Cell Painting now provide millions of images for systematic study. However, JUMP alone occupies 115 TB, and fragmented evaluation practices make systematic comparisons of representation methods impractical for many researchers. Here we present Nahual, an open-source framework for reproducible model deployment, and JUMP-lite, a 92.0 GB subset of JUMP that is approximately 1,250-fold smaller, selected to cover genetic modalities and compound annotations and reduced via lossy JPEG XL compression. Using these resources, we benchmark five representation methods, including classical features (CellProfiler) and deep learning models (MorphEM, OpenPhenom, SubCell, DINOv2). Moderate compression broadly retains signal relative to uncompressed images. Standardized phenotypic activity and consistency metrics reveal meaningful performance differences across methods. Together, JUMP-lite and Nahual provide a foundation for accessible, reproducible benchmarking of image-based cell representations.

q-bio.QM↗

arXiv2026

Neural Logic, Invariance, and the Retina---McCulloch and Pitts

This chapter reconstructs the McCulloch-Pitts program as a physics of neural computation rather than the familiar cartoon of a binary neuron. The 1943 logical calculus is developed in both directions: given a net, characterize the propositions realized by its activity; given an admissible logical expression, construct a net that realizes it. We recover the original distinction between thresholded excitatory summation and absolute inhibitory veto-one the weighted-threshold form cannot preserve for arbitrarily large excitatory inputs-and read unit-time delay as the physical realization of logical depth. Recurrence is treated exactly: an autonomous, deterministic network of finitely many binary units has a finite state space, so every trajectory eventually enters a periodic orbit-a fact about finite-state dynamics, not unbounded Turing computation. A single threshold element realizes only linearly separable Boolean functions, whereas finite feedforward networks of them synthesize any Boolean function on a finite domain. We then follows McCulloch and Pitts beyond threshold logic. The 1945 heterarchy paper turns cyclic preference into an obstruction to representation by a scalar utility. The 1947 work on universals asks how a physical network can identify inputs related by nuisance transformations, developed here via group averaging and feedback canonicalization. The 1959 frog-retina study makes the adequate-stimulus question experimental, revealing parallel invariant operations before the brain proper. Spike-triggered analysis shows how a nonlinearly driven neuron can have a vanishing first-order average while second-order statistics recover its hidden selectivity: methodological failure can masquerade as physiological absence. Modern mathematical tools are used without projecting their notation onto the historical papers, and limitations of the idealization are stated explicitly.

q-bio.NC↗

arXiv2026

PhyloGFN: Phylogenetic inference with generative flow networks

Phylogenetics is a branch of computational biology that studies the evolutionary relationships among biological entities. Its long history and numerous applications notwithstanding, inference of phylogenetic trees from sequence data remains challenging: the high complexity of tree space poses a significant obstacle for the current combinatorial and probabilistic techniques. In this paper, we adopt the framework of generative flow networks (GFlowNets) to tackle two core problems in phylogenetics: parsimony-based and Bayesian phylogenetic inference. Because GFlowNets are well-suited for sampling complex combinatorial structures, they are a natural choice for exploring and sampling from the multimodal posterior distribution over tree topologies and evolutionary distances. We demonstrate that our amortized posterior sampler, PhyloGFN, produces diverse and high-quality evolutionary hypotheses on real benchmark datasets. PhyloGFN is competitive with prior works in marginal likelihood estimation and achieves a closer fit to the target distribution than state-of-the-art variational inference methods. Our code is available at https://github.com/zmy1116/phylogfn.

q-bio.PE↗

arXiv2026

"More Is Different'' in Neural Circuits: Algebraic Emergence of Effective Theories in Canonical Recurrent Motifs of Biological Neuronal Networks

Canonical neural circuit motifs are usually described functionally: divisive normalization rescales population activity by a pooled signal, and winner-take-all competition selects one pattern through recurrent excitation and shared inhibition. We represent them, and their compositions, algebraically as finite transformation systems and analyze the transition monoids generated by their input-conditioned updates, distinguishing structure already present in a generator from structure that appears only through composition, and, on a joint state space, structure inherited from one factor from structure that lives on a joint configuration. Individually aperiodic updates can generate non-aperiodic monoids. In the WTA, every frozen-drive generator collapses to fixed points, yet short input sequences create local cycles of winner-dependent inhibitory gating: globally dissipative dynamics with a reversible action. The strongest result arises in WTA-to-DN composition. The composed monoid then contains a genuinely composite local cycle in which normalization state and the winner's gating state change together, although every primitive generator is aperiodic. Holonomy analysis certifies this as a group component of the Krohn-Rhodes cascade rather than an incidental cycle, and finds most group-carrying image sets on joint configurations, whereas the uncoupled product has none. An exhaustive interface sweep shows that the composite cycle is a property of the coupling rather than of a chosen map. If motifs are building blocks of neural computation, composing them is a form of programming: one chooses primitives and interfaces so that the generated algebra has the intended repertoire. The transition monoid is that repertoire - what a primitive presents to any later construction. Recurrent circuits are compositional transformation systems; their algebra constrains what they can be programmed to compute.

q-bio.NC↗