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2603.04149 2026-03-05 q-bio.NC

Topological Origin of the Diversity of Timescales in Recurrent Neural Circuits

Marco Zenari, Luca Taffarello, Luca Mazzucato, Amos Maritan, Samir Suweis

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英文摘要

Structural and functional heterogeneity are hallmarks of cortical circuits, from broad degree distributions in the mouse connectome to diverse intrinsic neuronal timescales. Yet a mechanistic link between connectivity heterogeneity and functional diversity is lacking. To bridge this gap, we introduce a random recurrent network in which connectivity is generated by a configuration model with tunable degree heterogeneity and synaptic weights exhibiting varying levels of correlation. Using generating-functional methods, we derive a heterogeneous dynamical mean-field theory (hDMFT) with degree-conditioned stochastic dynamics. The theory shows that the interaction of partial symmetry in the weights and degree heterogeneity induces a non-Markovian memory term in the form of an emergent self-coupling whose strength scales with degree and produces a broad distribution of activity timescales. We obtain analytic stability criteria demonstrating that degree heterogeneity lowers the critical gain and localizes unstable modes onto hubs. The resulting rich dynamical landscape includes silent, chaotic, and multistable regimes, which we uncover via spectral, replica, and Lyapunov exponent analyses. We highlight the computational benefits of the observed timescale heterogeneity by revealing that, under an external input drive featuring a broadband spectrum, slow hub neurons act as integrators, demixing slow input components. Finally, instantiating the model with the empirically measured topology from the MICrONS cubic-millimeter mouse connectome explains the broad range of single-neuron timescales and their positive correlation with in-degree observed in resting-state recordings. Our results provide a mechanistic link between connectome topology, neural dynamics, and computation, identifying hubs in partially symmetric networks as a natural substrate for multiplexed processing across timescales.

2603.04081 2026-03-05 cs.CV q-bio.QM

Revisiting the Role of Foundation Models in Cell-Level Histopathological Image Analysis under Small-Patch Constraints -- Effects of Training Data Scale and Blur Perturbations on CNNs and Vision Transformers

Hiroki Kagiyama, Toru Nagasaka, Yukari Adachi, Takaaki Tachibana, Ryota Ito, Mitsugu Fujita, Kimihiro Yamashita, Yoshihiro Kakeji

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英文摘要

Background and objective: Cell-level pathological image analysis requires working with extremely small image patches (40x40 pixels), far below standard ImageNet resolutions. It remains unclear whether modern deep learning architectures and foundation models can learn robust and scalable representations under this constraint. We systematically evaluated architectural suitability and data-scale effects for small-patch cell classification. Methods: We analyzed 303 colorectal cancer specimens with CD103/CD8 immunostaining, generating 185,432 annotated cell images. Eight task-specific architectures were trained from scratch at multiple data scales (FlagLimit: 256--16,384 samples per class), and three foundation models were evaluated via linear probing and fine-tuning after resizing inputs to 224x224 pixels. Robustness to blur was assessed using pre- and post-resize Gaussian perturbations. Results: Task-specific models improved consistently with increasing data scale, whereas foundation models saturated at moderate sample sizes. A Vision Transformer optimized for small patches (CustomViT) achieved the highest accuracy, outperforming all foundation models with substantially lower inference cost. Blur robustness was comparable across architectures, with no qualitative advantage observed for foundation models. Conclusion: For cell-level classification under extreme spatial constraints, task-specific architectures are more effective and efficient than foundation models once sufficient training data are available. Higher clean accuracy does not imply superior robustness, and large pre-trained models offer limited benefit in the small-patch regime.

2603.04074 2026-03-05 q-bio.QM

Dose-Dependent Cardiac Complexity Changes in Children Following Prenatal Glucocorticoid Exposure: Complementary Evidence from Multiscale Entropy Analysis and ECG Foundation Models

Nicolas B. Garnier, Michelle Dreiling, Valeska Kozik, Matthias Schwab, Florian Rakers, Martin G Frasch

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英文摘要

\noindent\textbf{Background} Prenatal glucocorticoid exposure alters cardiac development, but whether persistent cardiac effects in childhood follow a dose-response relationship remains unknown. We recently showed that ECG foundation models detect robust cardiac differences between steroid-exposed and control children, while traditional heart rate variability metrics lose significance after covariate adjustment. Here, we investigate the dose-response dimension using complementary analytical approaches. \noindent\textbf{Methods} We studied 49 children (ages 8--15) whose mothers received betamethasone during pregnancy for multiple sclerosis: 12 low-dose ({$<$}5\,g cumulative), 13 high-dose ({$\geq$}5\,g), and 24 controls. Five-minute ECG recordings during the Trier Social Stress Test yielded 251 observations. We computed 12 multiscale complexity features and tested 11 ECG foundation model (FM) dimensions using linear mixed models, Kruskal--Wallis tests with Dunn's post-hoc comparisons, Spearman correlations, and Jonckheere--Terpstra trend tests. \noindent\textbf{Findings} The binary exposed-versus-controls comparison showed no significant complexity effects ($p>0.39$). However, dose-based analysis revealed that high-dose children exhibited significantly faster entropy rate ($h$) decay rates than low-dose children ($p=0.031$); neither sample entropy nor approximate entropy decay rates reached significance ($p=0.18$ and $p=0.12$, respectively). Effects localized to the mental arithmetic stress segment (Kruskal--Wallis $p=0.005$; Dunn's $p=0.004$). A cross-condition robustness analysis confirmed that $h$ decay rate is invariant to input signal choice and normalization ($r>0.98$), while sample and approximate entropy are not. In contrast, the 11 FM dimensions showed weak dose-response evidence: only 1 of 22 covariate-adjusted contrasts survived FDR correction, with paradoxically stronger low-dose effects. \noindent\textbf{Interpretation} The entropy rate decay rate -- uniquely robust across input conditions -- reveals a dose-dependent effect on cardiac autonomic dynamics under cognitive stress, while FM dimensions detect a dose-independent morphological ``exposure fingerprint.'' These exploratory findings suggest a two-component model of prenatal glucocorticoid cardiac programming -- ~morphological (dose-independent) and dynamical (dose-dependent)~ -- providing more complete characterization than either approach alone. Given the small sample size, these results should be considered hypothesis-generating and require replication in larger cohorts.

2603.03870 2026-03-05 q-bio.NC nlin.AO

Two-phase quadratic integrate-and-fire neurons: Exact low-dimensional description for ensembles of finite-voltage neurons

Rok Cestnik

Comments 6 pages, 2 figures

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Journal ref
Physical Review Research 8, L012049 (2026)
英文摘要

We introduce a two-phase quadratic integrate-and-fire (QIF) neuron whose membrane potential evolves according to two alternating Riccati equations within finite bounds. This simple extension removes the unphysical voltage divergence of the standard QIF model while producing realistic spike waveforms. Despite this modification, the system retains an exact low-dimensional description in the thermodynamic limit, governed by a single complex Riccati equation. Expressions for collective quantities such as the firing rate and mean voltage remain compact and analytically tractable. Because the formalism preserves the mathematical structure of the standard QIF ensemble, it inherits its many generalizations and can serve as a drop-in replacement in existing mean-field frameworks, providing a more biologically plausible yet still exactly solvable neuronal model.

2603.03864 2026-03-05 q-bio.NC

Performance of Conventional EEG Biomarkers Across Different Clinical Phases of Major Depressive Disorder: A Comprehensive Evaluation

Feng Yan, Xuteng Wang, Shuyu Yang, Yue Zhao, Xiaobin Wong, Zhiren Wang

Comments 74 subjects, 3 groups, 3 conditions

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英文摘要

While EEG features differentiate Major Depressive Disorder (MDD) from healthy controls (HC), their clinical utility as biomarkers depends on a monotonic trajectory across the disease spectrum, from the acute (AC) phase to the maintenance (MA) phase and finally to the healthy baseline. However, the progression of the MA phase remains poorly understood in traditional marker analysis. Analyzing EEG data from 74 individuals (24 AC, 23 MA, and 27 HC), this study provides a comprehensive evaluation of classic ERP and resting-state indices across AC, MA, and HC groups. Our results demonstrate that almost no conventional metrics strictly satisfy the criterion of monotonic progression, likely due to profound inter-individual heterogeneity. These findings highlight the inherent limitations of group-level feature extraction and provide critical insights for developing future paradigms and algorithms to identify neurobiological markers with genuine clinical utility.

2603.03604 2026-03-05 cs.CV q-bio.QM

Tracking Feral Horses in Aerial Video Using Oriented Bounding Boxes

Saeko Takizawa, Tamao Maeda, Shinya Yamamoto, Hiroaki Kawashima

Comments Author's version of the paper presented at AROB-ISBC 2026

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Journal ref
Proc. of the Joint Symposium of AROB 31st and ISBC 11th (AROB-ISBC 2026), pp. 1580-1584, 2026
英文摘要

The social structures of group-living animals such as feral horses are diverse and remain insufficiently understood, even within a single species. To investigate group dynamics, aerial videos are often utilized to track individuals and analyze their movement trajectories, which are essential for evaluating inter-individual interactions and comparing social behaviors. Accurate individual tracking is therefore crucial. In multi-animal tracking, axis-aligned bounding boxes (bboxes) are widely used; however, for aerial top-view footage of entire groups, their performance degrades due to complex backgrounds, small target sizes, high animal density, and varying body orientations. To address this issue, we employ oriented bounding boxes (OBBs), which include rotation angles and reduce unnecessary background. Nevertheless, current OBB detectors such as YOLO-OBB restrict angles within a 180$^{\circ}$ range, making it impossible to distinguish head from tail and often causing sudden 180$^{\circ}$ flips across frames, which severely disrupts continuous tracking. To overcome this limitation, we propose a head-orientation estimation method that crops OBB-centered patches, applies three detectors (head, tail, and head-tail), and determines the final label through IoU-based majority voting. Experiments using 299 test images show that our method achieves 99.3% accuracy, outperforming individual models, demonstrating its effectiveness for robust OBB-based tracking.

2603.03603 2026-03-05 cs.CV q-bio.QM

Detection and Identification of Penguins Using Appearance and Motion Features

Kasumi Seko, Hiroki Kinoshita, Raj Rajeshwar Malinda, Hiroaki Kawashima

Comments Author's version of the paper presented at AROB-ISBC 2026

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Journal ref
Proc. of the Joint Symposium of AROB 31st and ISBC 11th (AROB-ISBC 2026), pp. 1585-1590, 2026
英文摘要

In animal facilities, continuous surveillance of penguins is essential yet technically challenging due to their homogeneous visual characteristics, rapid and frequent posture changes, and substantial environmental noise such as water reflections. In this study, we propose a framework that enhances both detection and identification performance by integrating appearance and motion features. For detection, we adapted YOLO11 to process consecutive frames to overcome the lack of temporal consistency in single-frame detectors. This approach leverages motion cues to detect targets even when distinct visual features are obscured. Our evaluation shows that fine-tuning the model with two-frame inputs improves mAP@0.5 from 0.922 to 0.933, outperforming the baseline, and successfully recovers individuals that are indistinguishable in static images. For identification, we introduce a tracklet-based contrastive learning approach applied after tracking. Through qualitative visualization, we demonstrate that the method produces coherent feature embeddings, bringing samples from the same individual closer in the feature space, suggesting the potential for mitigating ID switching.

2603.01752 2026-03-05 cs.LG q-bio.CB q-bio.GN

Causal Circuit Tracing Reveals Distinct Computational Architectures in Single-Cell Foundation Models: Inhibitory Dominance, Biological Coherence, and Cross-Model Convergence

Ihor Kendiukhov

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英文摘要

Motivation: Sparse autoencoders (SAEs) decompose foundation model activations into interpretable features, but causal feature-to-feature interactions across network depth remain unknown for biological foundation models. Results: We introduce causal circuit tracing by ablating SAE features and measuring downstream responses, and apply it to Geneformer V2-316M and scGPT whole-human across four conditions (96,892 edges, 80,191 forward passes). Both models show approximately 53 percent biological coherence and 65 to 89 percent inhibitory dominance, invariant to architecture and cell type. scGPT produces stronger effects (mean absolute d = 1.40 vs. 1.05) with more balanced dynamics. Cross-model consensus yields 1,142 conserved domain pairs (10.6x enrichment, p < 0.001). Disease-associated domains are 3.59x more likely to be consensus. Gene-level CRISPRi validation shows 56.4 percent directional accuracy, confirming co-expression rather than causal encoding.

2603.01682 2026-03-05 cs.SI q-bio.QM

Modeling and Analysis of Fish Interaction Networks under Projected Visual Stimuli

Hiroaki Kawashima, Raj Rajeshwar Malinda, Saeko Takizawa

Comments Author's version of the paper presented at AROB-ISBC 2026. v2: Contact information updated

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Journal ref
Proc. of the Joint Symposium of AROB 31st and ISBC 11th (AROB-ISBC 2026), pp. 1620-1624, 2026
英文摘要

This paper addresses the estimation of a dynamic interaction network, a network of influence among individuals, under projected visual stimuli to quantify the influences of inter-individual interactions and external stimuli on collective behavior. Building upon our previously proposed network estimation model, which assumes a Boids-type model and employs a sparse regression framework to infer inter-individual influence networks from trajectory data, we extend the formulation by introducing a stimulus term. This enables the model to capture how individuals react to and propagate externally projected visual stimuli within the group. The resulting framework allows simultaneous estimation of inter-individual and stimulus-related interaction strengths. We also introduce entropy-based indices to capture the possible biases of individuals' influence. Our experiments with fish schools under projector-based visual stimuli demonstrate the effectiveness of the proposed indices in quantifying schooling behavior and identifying influential individuals within the group, serving as the basis for real-time, interpretable metrics of collective dynamics.

2601.16151 2026-03-05 physics.bio-ph q-bio.BM q-bio.GN

In vitro binding energies capture Klf4 occupancy across the human genome

Anne Schwager, Jonas Neipel, Yahor Savich, Douglas Diehl, Frank Jülicher, Anthony A. Hyman, Stephan W. Grill

Comments A.S., J.N., and Y.S. contributed equally to this work. Update 2025/03: correction of a few typos

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英文摘要

Transcription factors (TFs) regulate gene expression by binding to specific genomic loci determined by DNA sequence. Their sequence specificity is commonly summarized by a consensus binding motif. However, eukaryotic genomes contain billions of low-affinity DNA sequences to which TFs associate with a sequence-dependent binding energy. We currently lack insight into how the genomic sequence defines this spectrum of binding energies and the resulting pattern of TF localization. Here, we set out to obtain a quantitative understanding of sequence-dependent TF binding to both motif and non-motif sequences. We achieve this by first pursuing accurate measurements of physical binding energies of the human TF Klf4 to a library of short DNA sequences in a fluorescence-anisotropy-based bulk competitive binding assay. Second, we show that the highly non-linear sequence dependence of Klf4 binding energies can be captured by combining a linear model of binding energies with an Ising model of the coupled recognition of nucleotides by a TF. We find that this statistical mechanics model parametrized by our in vitro measurements captures Klf4 binding patterns on individual long DNA molecules stretched in the optical tweezer, and is predictive for Klf4 occupancy across the entire human genome without additional fit parameters.

2511.01960 2026-03-05 stat.OT q-bio.OT

Towards a Unified Framework for Statistical and Mathematical Modeling

Paul N Zivich

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Within the biological, physical, and social sciences, there are two broad quantitative traditions: statistical and mathematical modeling. Both traditions have the common pursuit of advancing our scientific knowledge, but these traditions have developed largely independently using distinct languages and inferential frameworks. This paper uses the notion of identification from causal inference, a field originating from the statistical modeling tradition, to develop a shared language. I first review foundational identification results for statistical models and then extend these ideas to mathematical models. Central to this framework is the use of bounds, ranges of plausible numerical values, to analyze both statistical and mathematical models. I discuss the implications of this perspective for the interpretation, comparison, and integration of different modeling approaches, and illustrate the framework with a simple pharmacodynamic model for hypertension. To conclude, I describe areas where the approach taken here should be extended in the future. By formalizing connections between statistical and mathematical modeling, this work contributes to a shared framework for quantitative science. My hope is that this work will advance interactions between these two traditions.

2510.02903 2026-03-05 cs.LG q-bio.CB

Learning Explicit Single-Cell Dynamics Using ODE Representations

Jan-Philipp von Bassewitz, Adeel Pervez, Marco Fumero, Matthew Robinson, Theofanis Karaletsos, Francesco Locatello

Comments 27 pages, 11 figures

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Journal ref
Proceedings of the Fourteenth International Conference on Learning Representations (ICLR 2026)
英文摘要

Modeling the dynamics of cellular differentiation is fundamental to advancing the understanding and treatment of diseases associated with this process, such as cancer. With the rapid growth of single-cell datasets, this has also become a particularly promising and active domain for machine learning. Current state-of-the-art models, however, rely on computationally expensive optimal transport preprocessing and multi-stage training, while also not discovering explicit gene interactions. To address these challenges we propose Cell-Mechanistic Neural Networks (Cell-MNN), an encoder-decoder architecture whose latent representation is a locally linearized ODE governing the dynamics of cellular evolution from stem to tissue cells. Cell-MNN is fully end-to-end (besides a standard PCA pre-processing) and its ODE representation explicitly learns biologically consistent and interpretable gene interactions. Empirically, we show that Cell-MNN achieves competitive performance on single-cell benchmarks, surpasses state-of-the-art baselines in scaling to larger datasets and joint training across multiple datasets, while also learning interpretable gene interactions that we validate against the TRRUST database of gene interactions.

2509.03654 2026-03-05 math.DS nlin.CG q-bio.MN

Dominant vertices and attractors' landscape for Boolean networks

Andrea España, William Funez, Edgardo Ugalde

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In previous works, we introduced the notion of dominant vertices in the context of dynamical systems on networks. This is a set of nodes in the underlying network whose evolution determines the whole network's dynamics after a transient time. In this paper, we focus on the case of Boolean networks. We define a reduced graph on the dominant vertices and an induced dynamics on this graph, which we prove is asymptotically equivalent to the original Boolean dynamics. Asymptotic conjugacy ensures that the systems, restricted to their respective attractors, are dynamically equivalent. For a significant class of networks, the induced dynamics is indeed a reduction of the original system. In these cases, the reduction, which is obtained from the structure of dominant vertices, supplies a more tractable system with the same structure of attractors as the original one. Furthermore, the structure of the induced system allows us to establish bounds on the number and period of the attractors, as well as on the reduction of the basin's sizes and transient lengths. We illustrate this reduction by considering a class of networks, which we call clover networks, whose dominant set is a singleton. To get insight into the structure of the basins of attraction of Boolean networks with a single dominant vertex, we complement this work with a numerical exploration of the behavior of a parametrized ensemble of systems of this kind.

2508.04735 2026-03-05 q-bio.QM cs.AI

ERDES: A Benchmark Video Dataset for Retinal Detachment and Macular Status Classification in Ocular Ultrasound

Yasemin Ozkut, Pouyan Navard, Srikar Adhikari, Elaine Situ-LaCasse, Josie Acuña, Adrienne Yarnish, Alper Yilmaz

Comments Under Review, https://github.com/OSUPCVLab/ERDES

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英文摘要

Retinal detachment (RD) is a vision-threatening condition that requires prompt intervention to preserve sight. A critical factor in treatment urgency and visual prognosis is macular involvement -- whether the macula is intact or detached. Point-of-care ultrasound (POCUS) is a fast, non-invasive and cost-effective imaging tool commonly used to detect RD in various clinical settings. However, its diagnostic utility is limited by the need for expert interpretation, especially in resource-limited environments. Deep learning has the potential to automate RD detection on ultrasound, but there are no clinically available models, and prior research has not addressed macular status -- an essential distinction for surgical prioritization. Additionally, no public dataset currently supports macular-based RD classification using ultrasound video. We introduce Eye Retinal DEtachment ultraSound (ERDES), the first open-access dataset of ocular ultrasound clips labeled for (i) presence of RD and (ii) macula-detached vs. macula-intact status. ERDES enables machine learning development for RD detection. We also provide baseline benchmarks by training 40 models across eight architectures, including 3D convolutional networks and transformer-based models.

2506.15581 2026-03-05 q-bio.MN

Dynamics of attractor transitions in Boolean networks under noise

Byungjoon Min, Jeehye Choi, Reinhard Laubenbacher

Comments 8 pages, 5 figures

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Journal ref
Chaos 36, 023142 (2026)
英文摘要

Biological systems operate under persistent noise, which can alter system states and induce transitions between attractors. Here, we study the attractor dynamics of Boolean networks focusing on the transitions between attractors induced by noise. By computing transition probabilities between attractors, we present methods at the attractor level to determine dominance, stability, and diversity of attractors, and systematically compare local and global noise. Whereas global noise leads to attractor behavior dictated primarily by basin sizes, local noise produces structured transition patterns characterized by enhanced stability, non-trivial dominance patterns, and broader exploration of the attractor space. Our work offers insight into the dynamics of attractors, showing the importance of transition patterns under noise.

2505.07053 2026-03-05 q-bio.MN physics.bio-ph q-bio.SC

The Dynamics of Inducible Genetic Circuits

Zitao Yang, Rebecca J. Rousseau, Sara D. Mahdavi, Hernan G. Garcia, Rob Phillips

Comments 60 pages, 38 figures

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英文摘要

Genes are connected in complex networks of interactions where often the product of one gene is a transcription factor that alters the expression of another. Many of these networks are based on a few fundamental motifs leading to switches and oscillators of various kinds. And yet, there is more to the story than which transcription factors control these various circuits. These transcription factors are often themselves under the control of effector molecules that bind them and alter their level of activity. Traditionally, much beautiful work has shown how to think about the stability of the different states achieved by these fundamental regulatory architectures by examining how parameters such as transcription rates, degradation rates and dissociation constants tune the circuit, giving rise to behavior such as bistability. However, such studies explore dynamics without asking how these quantities are altered in real time in living cells as opposed to at the fingertips of the synthetic biologist's pipette or on the computational biologist's computer screen. In this paper, we make a departure from the conventional dynamical systems view of these regulatory motifs by using statistical mechanical models to focus on endogenous signaling knobs such as effector concentrations rather than on the convenient but more experimentally remote knobs such as dissociation constants, transcription rates and degradation rates that are often considered. We also contrast the traditional use of Hill functions to describe transcription factor binding with more detailed thermodynamic models. This approach provides insights into how biological parameters are tuned to control the stability of regulatory motifs in living cells, sometimes revealing quite a different picture than is found by using Hill functions and tuning circuit parameters by hand.

2603.03591 2026-03-05 q-bio.PE

Mutation Rate Variation Across Genomic Regions in \textit{Arabidopsis thaliana}

Elisa Heinrich-Mora, Marcus W. Feldman

Comments 18 pages, 3 figures

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英文摘要

In population genetics, mutation rate is often treated as a homogeneous parameter across the genome. Empirical evidence, however, shows systematic variation across genomic contexts associated with chromatin organization and epigenomic features. Using gene-level de novo mutation data from Arabidopsis thaliana, we test whether chromatin features predict not only the mean per-base mutation rate but also its variability across genes. To reduce heterogeneity in selective regime, we restrict analysis to essential and lethal loci subject to strong purifying selection. Across complementary multivariable models including heteroskedasticity-robust linear regression, length-weighted regression, and Poisson generalized linear models with exposure offsets, histone marks associated with active transcription (H3K4me1, H3K4me3, H3K36ac) are consistently associated with lower mean mutation rates and substantially reduced between-gene variance. GC content shows little association with the mean once chromatin predictors are controlled but is positively associated with mutation-rate variability. Estimates of skewness and kurtosis reveal no significant higher-order structure attributable to epigenomic predictors. A standardized Tajima's $D$ statistic yields directionally consistent but statistically underpowered associations with both the mean and variance of gene-level mutation rates. These results indicate that mutation rate is systematically structured by chromatin state within functionally constrained genes and suggest that evolutionary processes may act not only on expected mutation rate but also on its variability across loci.

2603.03547 2026-03-05 physics.bio-ph q-bio.GN

Learning functional groups in complex microbiomes

Matthew S Schmitt, Kiseok Lee, Freddy Bunbury, Joseph A Landsittel, Vincenzo Vitelli, Seppe Kuehn

Comments 44 pages, 5 main figures, 17 supplementary figures

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英文摘要

From soil to the gut, communities composed of thousands of microbes perform functions such as carbon sequestration and immune system regulation. Here, we introduce a data-driven approach that explains how community function can be traced to just a few groups of microbes or genes. In gut communities, our neural-network based clustering algorithm correctly recovers known functional groups. In the ocean metagenome, it distills ~500 gene modules down to three sparse groups highlighting survival strategies at different depths. In soils, it distills ~4400 bacterial species into two groups that enter a mathematical model of nitrate metabolism. By combining interpretable ML with strain isolation and sequencing experiments, we connect the metabolic specialization of each group to community-wide responses to perturbations. This integrated approach yields simple structure-function maps of microbiomes, allowing the discovery of molecular mechanisms underlying human and environmental health. More broadly, we illustrate how to do function-informed dimensionality reduction in biology.

2603.03521 2026-03-05 q-bio.PE

On estimating the effective sample size of phylogenetic trees in an autocorrelated chain

Jonathan Klawitter, Lars Berling, Jordan Douglas, Dong Xie, Alexei J. Drummond

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英文摘要

Estimating the effective sample size (ESS) is fundamental in Bayesian phylogenetic inference to properly account for autocorrelation in MCMC samples. While methods for continuous parameters are well established, the discrete and high-dimensional nature of treespace poses substantial challenges. Here, we compare existing tree ESS estimators with novel approaches that leverage tractable tree distributions, specifically Conditional Clade Distributions (CCDs), as well as a new probabilistic estimator based on clade frequency differences between independent chains. Using simulated chains with known ESS bounds, we assess estimator accuracy and evaluate their stability and robustness on simulated and real datasets. We further examine how multimodality in posterior distributions and poor mixing can substantially affect ESS estimates, highlighting the need for careful interpretation. Our CCD-based estimators perform comparably to existing approaches, with two methods showing lower variance by averaging across multiple estimates. In contrast, the probabilistic estimator and two previously recommended methods incur prohibitive computational costs for long chains. Together, these results provide guidance for reliable and efficient tree ESS estimation in complex phylogenetic analyses.

2603.03493 2026-03-05 q-bio.MN cs.LG

Quantifying Ranking Instability Across Evaluation Protocol Axes in Gene Regulatory Network Benchmarking

Ihor Kendiukhov

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Benchmark rankings are routinely used to justify scientific claims about method quality in gene regulatory network (GRN) inference, yet the stability of these rankings under plausible evaluation protocol choices is rarely examined. We present a systematic diagnostic framework for measuring ranking instability under protocol shift, including decomposition tools that separate base rate effects from discrimination effects. Using existing single cell GRN benchmark outputs across three human tissues and six inference methods, we quantify pairwise reversal rates across four protocol axes: candidate set restriction (16.3 percent, 95 percent CI 11.0 to 23.4 percent), tissue context (19.3 percent), reference network choice (32.1 percent), and symbol mapping policy (0.0 percent). A permutation null confirms that observed reversal rates are far below random order expectations (0.163 versus null mean 0.500), indicating partially stable but non invariant ranking structure. Our decomposition reveals that reversals are driven by changes in the relative discrimination ability of methods rather than by base rate inflation, a finding that challenges a common implicit assumption in GRN benchmarking. We propose concrete reporting practices for stability aware evaluation and provide a diagnostic toolkit for identifying method pairs at risk of reversal.

2603.03476 2026-03-05 q-bio.NC cs.DS cs.IR cs.NE

Stringology-Based Motif Discovery from EEG Signals: an ADHD Case Study

Anat Dahan, Samah Ghazawi

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英文摘要

We propose a novel computational framework for analyzing electroencephalography (EEG) time series using methods from stringology, the study of efficient algorithms for string processing, to systematically identify and characterize recurrent temporal patterns in neural signals. The primary aim is to introduce quantitative measures to understand neural signal dynamics, with the present findings serving as a proof-of-concept. The framework adapts order-preserving matching (OPM) and Cartesian tree matching (CTM) to detect temporal motifs that preserve relative ordering and hierarchical structure while remaining invariant to amplitude scaling. This approach provides a temporally precise representation of EEG dynamics that complements traditional spectral and global complexity analyses. To evaluate its utility, we applied the framework to multichannel EEG recordings from individuals with attention-deficit/hyperactivity disorder (ADHD) and matched controls using a publicly available dataset. Highly recurrent, group-specific motifs were extracted and quantified using both OPM and CTM. The ADHD group exhibited significantly higher motif frequencies, suggesting increased repetitiveness in neural activity. OPM analysis revealed shorter motif lengths and greater gradient instability in ADHD, reflected in larger mean and maximal inter-sample amplitude changes. CTM analysis further demonstrated reduced hierarchical complexity in ADHD, characterized by shallower tree structures and fewer hierarchical levels despite comparable motif lengths. These findings suggest that ADHD-related EEG alterations involve systematic differences in the structure, stability, and hierarchical organization of recurrent temporal patterns. The proposed stringology-based motif framework provides a complementary computational tool with potential applications for objective biomarker development in neurodevelopmental disorders.

2603.03414 2026-03-05 q-bio.NC

Cognitive Dark Matter: Measuring What AI Misses

Patrick J. Mineault, Thomas L. Griffiths, Sean Escola

Comments 11 pages, 3 figures

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We propose that the jagged intelligence landscape of modern AI systems arises from a missing training signal that we call "cognitive dark matter" (CDM): brain functions that meaningfully shape behavior yet are hard to infer from behavior alone. We identify key CDM domains-metacognition, cognitive flexibility, episodic memory, lifelong learning, abductive reasoning, social and common-sense reasoning, and emotional intelligence-and present evidence that current AI benchmarks and large-scale neuroscience datasets are both heavily skewed toward already-mastered capabilities, with CDM-loaded functions largely unmeasured. We then outline a research program centered on three complementary data types designed to surface CDM for model training: (i) latent variables from large-scale cognitive models, (ii) process-tracing data such as eye-tracking and think-aloud protocols, and (iii) paired neural-behavioral data. These data will enable AI training on cognitive process rather than behavioral outcome alone, producing models with more general, less jagged intelligence. As a dual benefit, the same data will advance our understanding of human intelligence itself.

2603.03362 2026-03-05 q-bio.NC

Metric-Topology Factorization: A Computational Framework for Hippocampal-Neocortical Intelligence

Xin Li

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The brain achieves stability and plasticity in a topologically complex, shifting world through Metric-Topology Factorization (MTF), separating discrete topological indexing for context selection from continuous metric condensation for local inference. Semantically rich environments defy single globally contractive geometries, causing obstructions under shifts, so intelligence factorizes these: the hippocampus provides sparse signatures indexing manifold identity, while the neocortex untangles geometry hierarchically. In the ventral stream, a dynamic-programming-like process quotients symmetries (e.g., translation, scale), transforming non-convex sensory mazes into separable bowls. Offline replay and consolidation amortize transformations for rapid task switching. Dreaming in REM involves stochastic hippocampal traversal to expose and regularize latent structures. Consciousness arises from resolving topological uncertainty into stable embeddings, with awareness for unamortized states. Evolutionarily, transitions like sensorimotor control to language expand topological complexity, demanding advanced indexing-metric separation. Intelligence emerges via recalibrating context-specific geometries, converting global navigation into local dynamics, not deeper search.

2603.03358 2026-03-05 q-bio.NC

Contextuality, Incompatibility, and Intra-System Entanglement of Mental Markers

Andrei Khrennikov, Felix Benninger, Oded Shor

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英文摘要

Over the past two decades, quantum-like modeling (QLM) has emerged as a powerful framework for describing non-classical features of cognition and decision-making. Rather than assuming physical quantum processes in the brain, QLM employs the Hilbert space formalism to model contextuality, incompatibility of mental observables, and entanglement-like correlations. In this paper, we develop a quantum-informational model of mental markers within the broader I-field (information field) approach. We propose that, under conditions of information overload and limited cognitive resources, individuals primarily respond not to detailed semantic content but to compact content labels - mental markers - carrying cognitive and affective components. We formalize mental markers as structured quantum-like states and analyze the nonclassical correlations between their cognitive and affective components using the Contextuality-Incompatibility-Entanglement triad. Special attention is given to intra-system entanglement between rational (cognitive) evaluation and emotional (affective) coloring, accounting for context-dependent judgments, order effects, and affect-driven decision shifts. Illustrative examples with psychological interpretation and experimental perspectives are provided. An Appendix briefly discusses neurobiological analogues of information overload in neural networks, highlighting structural parallels with the proposed marker-based framework; coupling to the origin and diagnostics of neurological diseases is analyzed. The paper contributes to QLM by distinguishing inter-system and intra-system entanglement and by demonstrating that cognitive - affective entanglement constitutes a fundamental structural feature of mental markers in socially mediated information environments.

2603.03355 2026-03-05 q-bio.NC cs.AI

Inhibitory Cross-Talk Enables Functional Lateralization in Attention-Coupled Latent Memory

Hong Jeong

Comments 10 pages, 3 figures, conference style

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英文摘要

We present a memory-augmented transformer in which attention serves simultaneously as a retrieval, consolidation, and write-back operator. The core update, $A^\top A V W$, re-grounds retrieved values into persistent memory slots via the Gram matrix $A^\top A$, providing a principled tripartite projection: observation space $\to$ latent memory $\to$ supervised transformation. We partition the memory into lateralized left and right banks coupled through a sign-controlled cross-talk matrix $W_s$, and show that the sign of this coupling is decisive for specialization. Excitatory cross-talk ($s=+1$) causes bank-dominance collapse: one bank monopolises all inputs and $\mathcal{P}_{ct} \to 0.5$, despite lowering task loss. Inhibitory cross-talk ($s=-1$), motivated by the net inhibitory effect of callosal projections in human cortex, actively suppresses contralateral bank activation and achieves saturated specialization ($\mathcal{D}_{sep} = \pm 1.00$, $\mathcal{P}_{ct} \approx 0$). On a controlled symbolic benchmark combining an episodic bijection cipher (requiring associative recall) with a strict arithmetic progression (requiring rule extraction), the inhibitory model reduces cipher-domain loss by $124{\times}$ over the baseline while matching it on the arithmetic domain, confirming that persistent lateralized memory is necessary for episodic recall but not for rule-based prediction.

2603.03350 2026-03-05 q-bio.QM cs.LG cs.SD eess.AS

Automated Measurement of Geniohyoid Muscle Thickness During Speech Using Deep Learning and Ultrasound

Alisher Myrgyyassov, Bruce Xiao Wang, Yu Sun, Shuming Huang, Zhen Song, Min Ney Wong, Yongping Zheng

Comments 6 pages, including references and acknowledgements. Submitted to Interspeech 2026

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英文摘要

Manual measurement of muscle morphology from ultrasound during speech is time-consuming and limits large-scale studies. We present SMMA, a fully automated framework that combines deep-learning segmentation with skeleton-based thickness quantification to analyze geniohyoid (GH) muscle dynamics. Validation demonstrates near-human-level accuracy (Dice = 0.9037, MAE = 0.53 mm, r = 0.901). Application to Cantonese vowel production (N = 11) reveals systematic patterns: /a:/ shows significantly greater GH thickness (7.29 mm) than /i:/ (5.95 mm, p < 0.001, Cohen's d > 1.3), suggesting greater GH activation during production of /a:/ than /i:/, consistent with its role in mandibular depression. Sex differences (5-8% greater in males) reflect anatomical scaling. SMMA achieves expert-validated accuracy while eliminating the need for manual annotation, enabling scalable investigations of speech motor control and objective assessment of speech and swallowing disorders.

2603.03345 2026-03-05 q-bio.NC physics.comp-ph quant-ph

Characterization of Phase Transitions in a Lipkin-Meshkov-Glick Quantum Brain Model

Elvira Romera, Joaquín J. Torres

Comments 20 pages, 9 figures

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英文摘要

In this work we analyze the emergence of phase transitions in a quantum brain model inspired by the Lipkin-Meshkov-Glick framework, where biologically motivated synaptic feedback modulates the collective interaction in a nonlinear and state-dependent manner. We demonstrate that incorporating this retroactive mechanism substantially reshapes the phase structure, yielding an expansion of the paramagnetic phase at the expense of the ferromagnetic phases relative to the feedback-free scenario. This effect is markedly enhanced in the presence of a longitudinal field, as the feedback couples directly to the longitudinal magnetization, leading to an appreciable displacement of the critical boundaries. We characterize the ensuing transitions from a phase-space perspective by means of the ground-state Husimi distribution and the Wehrl entropy, which provide a robust diagnosis of qualitative changes in localization and enable a quantitative assessment of feedback-induced deformations of the phase diagram. Additionally, we perform an explicit dynamical analysis based on mean-field equations for the collective-spin orientation self-consistently coupled to the synaptic dynamics, which reproduces with high fidelity the quantum time evolution of collective observables for the protocols considered. Overall, these findings substantiate the suitability of this quantum brain model as a controlled theoretical framework for elucidating how synaptic plasticity mechanisms can parametrically tune and reshape collective criticality.

2603.03343 2026-03-05 q-bio.NC cs.AI cs.LG

Neuro-Symbolic Decoding of Neural Activity

Yanchen Wang, Joy Hsu, Ehsan Adeli, Jiajun Wu

Comments ICLR 2026. First two authors contributed equally

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英文摘要

We propose NEURONA, a neuro-symbolic framework for fMRI decoding and concept grounding in neural activity. Leveraging image- and video-based fMRI question-answering datasets, NEURONA learns to decode interacting concepts from visual stimuli based on patterns of fMRI responses, integrating symbolic reasoning and compositional execution with fMRI grounding across brain regions. We demonstrate that incorporating structural priors (e.g., compositional predicate-argument dependencies between concepts) into the decoding process significantly improves both decoding accuracy over precise queries, and notably, generalization to unseen queries at test time. With NEURONA, we highlight neuro-symbolic frameworks as promising tools for understanding neural activity.

2603.03342 2026-03-05 eess.IV cs.AI q-bio.BM

Cryo-SWAN: the Multi-Scale Wavelet-decomposition-inspired Autoencoder Network for molecular density representation of molecular volumes

Rui Li, Artsemi Yushkevich, Mikhail Kudryashev, Artur Yakimovich

Comments 16 pages, 5 figures

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英文摘要

Learning robust representations of 3D shapes from voxelized data is essential for advancing AI methods in biomedical imaging. However, most contemporary 3D computer vision approaches operate on point clouds, meshes, or octrees, while volumetric density maps, the native format of structural biology and cryo-EM, remain comparatively underexplored. We present Cryo-SWAN, a voxel-based variational autoencoder inspired by multi-scale wavelet decomposition. The model performs conditional coarse-to-fine latent encoding and recursive residual quantization across perception scales, enabling accurate capture of both global geometry and high-frequency structural detail in molecular density volumes. Evaluated on ModelNet40, BuildingNet, and a newly curated dataset of cryo-EM volumes, ProteinNet3D, Cryo-SWAN consistently improves reconstruction quality over state-of-the-art 3D autoencoders. We demonstrate that the molecular densities organize in learned latent space according to shared geometric features, while integration with diffusion models enables denoising and conditional shape generation. Together, Cryo-SWAN is a practical framework for data-driven structural biology and volumetric imaging.

2603.01387 2026-03-05 q-bio.NC cs.IT math.IT

An Information-Theoretic Framework For Optimizing Experimental Design To Distinguish Probabilistic Neural Codes

Po-Chen Kuo, Edgar Y. Walker

Comments Accepted to The Fourteenth International Conference on Learning Representations (ICLR 2026)

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英文摘要

The Bayesian brain hypothesis has been a leading theory in understanding perceptual decision-making under uncertainty. While extensive psychophysical evidence supports the notion of the brain performing Bayesian computations, how uncertainty information is encoded in sensory neural populations remains elusive. Specifically, two competing hypotheses propose that early sensory populations encode either the likelihood function (exemplified by probabilistic population codes) or the posterior distribution (exemplified by neural sampling codes) over the stimulus, with the key distinction lying in whether stimulus priors would modulate the neural responses. However, experimentally differentiating these two hypotheses has remained challenging, as it is unclear what task design would effectively distinguish the two. In this work, we present an information-theoretic framework for optimizing the task stimulus distribution that would maximally differentiate competing probabilistic neural codes. To quantify how distinguishable the two probabilistic coding hypotheses are under a given task design, we derive the information gap--the expected performance difference when likelihood versus posterior decoders are applied to neural populations--by evaluating the Kullback-Leibler divergence between the true posterior and a task-marginalized surrogate posterior. Through extensive simulations, we demonstrate that the information gap accurately predicts decoder performance differences across diverse task settings. Critically, maximizing the information gap yields stimulus distributions that optimally differentiate likelihood and posterior coding hypotheses. Our framework enables principled, theory-driven experimental designs with maximal discriminative power to differentiate probabilistic neural codes, advancing our understanding of how neural populations represent and process sensory uncertainty.