arXiv Quantitative Biology @arxiv_bio@qoto.org

Deep neural networks (DNNs) once showed increasing alignment with primate neural responses as they improved on computer vision benchmarks. This trend raised the exciting possibility that better models of biological vision would come as a byproduct of the deep learning revolution in artificial intelligence. However, the trend has reversed over recent years as DNNs have scaled to human or superhuman recognition accuracy, a divergence that may stem from modern DNNs learning to rely on different visual features than primates to solve tasks. Where will better computational models of biological vision come from? We propose that vision science must break from artificial intelligence to develop algorithms that are designed with biological visual systems in mind instead of internet data benchmarks. We predict that the next generation of deep learning models of biological vision will be trained with data diets, training routines, and objectives that are closer to those that shape human vision than those that are in use today.

This study presents a novel mathematical model derived from cohomology, leveraging the KEEL-proven theorem that establishes cohomology as tautological, generated by boundary classes of curves with fixed dual graphs. Simplicial complexes are constructed using skew-commutative graded algebra, and the structure theorem is applied to connect distinct homologies, enabling precise interpretations of the resulting geometric forms. The proposed model is utilized for protein structure analysis and prediction, with a specific application to the Flagellar Motor structure. This approach offers new insights into the geometric and algebraic foundations of biological macromolecular modeling, highlighting its potential for advancement in structural biology.

Automating the annotation of benthic imagery (i.e., images of the seafloor and its associated organisms, habitats, and geological features) is critical for monitoring rapidly changing ocean ecosystems. Deep learning approaches have succeeded in this purpose; however, consistent annotation remains challenging due to ambiguous seafloor images, potential inter-user annotation disagreements, and out-of-distribution samples. Marine scientists implementing deep learning models often obtain predictions based on one-hot representations trained using a cross-entropy loss objective with softmax normalization, resulting with a single set of model parameters. While efficient, this approach may lead to overconfident predictions for context-challenging datasets, raising reliability concerns that present risks for downstream tasks such as benthic habitat mapping and marine spatial planning. In this study, we investigated classification uncertainty as a tool to improve the labeling of benthic habitat imagery. We developed a framework for two challenging sub-datasets of the recently publicly available BenthicNet dataset using Bayesian neural networks, Monte Carlo dropout inference sampling, and a proposed single last-layer committee machine. This approach resulted with a > 95% reduction of network parameters to obtain per-sample uncertainties while obtaining near-identical performance compared to computationally more expensive strategies such as Bayesian neural networks, Monte Carlo dropout, and deep ensembles. The method proposed in this research provides a strategy for obtaining prioritized lists of uncertain samples for human-in-the-loop interventions to identify ambiguous, mislabeled, out-of-distribution, and/or difficult images for enhancing existing annotation tools for benthic mapping and other applications.

Automated breast cancer detection via computer vision techniques is challenging due to the complex nature of breast tissue, the subtle appearance of cancerous lesions, and variations in breast density. Mainstream techniques primarily focus on visual cues, overlooking complementary patient-specific textual features that are equally important and can enhance diagnostic accuracy. To address this gap, we introduce Multi-modal Cancer Detection Network (MMDCNet) that integrates visual cues with clinical data to improve breast cancer detection. Our approach processes medical images using computer vision techniques while structured patient metadata patterns are learned through a custom fully connected network. The extracted features are fused to form a comprehensive representation, allowing the model to leverage both visual and clinical information. The final classifier is trained based on the joint features embedding space of visual and clinical cues and experiments prove enhanced performance, improving accuracy from 79.38\% to 90.87\% on a Mini-DDSM dataset. Additionally, our approach achieves 97.05\% accuracy on an image-only dataset, highlighting the robustness and effectiveness of visual feature extraction. These findings emphasise the potential of multi-modal learning in medical diagnostics, paving the way for future research on optimising data integration strategies and refining AI-driven clinical decision support systems.

In this study, we built an end-to-end tumor-infiltrating lymphocytes (TILs) assessment pipeline within QuPath, demonstrating the potential of easily accessible tools to perform complex tasks in a fully automatic fashion. First, we trained a pixel classifier to segment tumor, tumor-associated stroma, and other tissue compartments in breast cancer H&E-stained whole-slide images (WSI) to isolate tumor-associated stroma for subsequent analysis. Next, we applied a pre-trained StarDist deep learning model in QuPath for cell detection and used the extracted cell features to train a binary classifier distinguishing TILs from other cells. To evaluate our TILs assessment pipeline, we calculated the TIL density in each WSI and categorized them as low, medium, or high TIL levels. Our pipeline was evaluated against pathologist-assigned TIL scores, achieving a Cohen's kappa of 0.71 on the external test set, corroborating previous research findings. These results confirm that existing software can offer a practical solution for the assessment of TILs in H&E-stained WSIs of breast cancer.

Mobile genetic elements like conjugative plasmids play a crucial role in shaping the genetic content and population dynamics of bacterial species. Bacterial populations often contain not one, but multiple co-circulating MGEs, which modify each other's population dynamics in a myriad of ways. Mathematical modeling is a powerful tool to gain intuition about the expected eco-evolutionary dynamics in a biological system with many interacting players. Here, we detail how to develop a mathematical model of plasmid co-infection, how to implement this computationally, and we give examples of what can be learned from such models.

Malignant gliomas (MGs), particularly glioblastoma, are among the most aggressive brain tumors, with limited treatment options and a poor prognosis. Maximal safe resection and the so-called Stupp protocol are the standard first-line therapies. Despite combining radiotherapy and chemotherapy in an intensive manner, it provides limited survival benefits over radiation therapy alone, underscoring the need for innovative therapeutic strategies. Emerging evidence suggests that alternative dosing schedules, such as less aggressive regimens with extended intervals between consecutive treatment applications, may improve outcomes, enhancing survival, delaying the emergence of resistance, and minimizing side effects. In this study, we develop, calibrate, and validate in animal models a novel ordinary differential equation-based mathematical model, using in vivo data to describe MG dynamics under combined chemoradiotherapy. The proposed model incorporates key biological processes, including cancer cell dormancy, phenotypic switching, drug resistance through persister cells, and treatment-induced effects. Through in silico trials, we identified optimized combination treatment protocols that may outperform the standard Stupp protocol. Finally, we computationally extrapolated the results obtained from the in vivo animal model to humans, showing up to a four-fold increase in median survival with protracted administration protocols in silico. Although further experimental and clinical validation is required, our framework provides a computational foundation to optimize and personalize treatment strategies for MG and potentially other cancers with similar biological mechanisms.

The human brain is a complex dynamical system which displays a wide range of macroscopic and mesoscopic patterns of neural activity, whose mechanistic origin remains poorly understood. Whole-brain modelling allows us to explore candidate mechanisms causing the observed patterns. However, it is not fully established how the choice of model type and the networks' resolution influence the simulation results, hence, it remains unclear, to which extent conclusions drawn from these results are limited by modelling artefacts. Here, we compare the dynamics of a biophysically realistic, linear-nonlinear cascade model of whole-brain activity with a phenomenological Wilson-Cowan model using three structural connectomes based on the Schaefer parcellation scheme with 100, 200, and 500 nodes. Both neural mass models implement the same mechanistic hypotheses, which specifically address the interaction between excitation, inhibition, and a slow adaptation current, which affects the excitatory populations. We quantify the emerging dynamical states in detail and investigate how consistent results are across the different model variants. Then we apply both model types to the specific phenomenon of slow oscillations, which are a prevalent brain rhythm during deep sleep. We investigate the consistency of model predictions when exploring specific mechanistic hypotheses about the effects of both short- and long-range connections and of the antero-posterior structural connectivity gradient on key properties of these oscillations. Overall, our results demonstrate that the coarse-grained dynamics are robust to changes in both model type and network resolution. In some cases, however, model predictions do not generalize. Thus, some care must be taken when interpreting model results.

Terracettes, striking, step-like landforms that stripe steep, vegetated hillslopes, have puzzled scientists for more than a century. Competing hypotheses invoke either slow mass-wasting or the relentless trampling of grazing animals, yet no mechanistic model has linked hoof-scale behavior to landscape-scale form. Here we bridge that gap with an active-walker model in which ungulates are represented as stochastic foragers moving on an erodible slope. Each agent weighs the energetic cost of climbing against the benefit of fresh forage; every hoof-fall compacts soil and lowers local biomass, subtly reshaping the energy landscape that guides subsequent steps. Over time, these stigmergic feedbacks concentrate traffic along cross-slope paths that coalesce into periodic tread-and-riser bands, morphologically analogous to natural terracettes. Our model illustrates how local foraging rules governing movement and substrate feedback can self-organize into large-scale topographic patterns, highlighting the wider role of decentralized biological processes in sculpting terrestrial landscapes.

Neurotensin receptor 1 (NTSR1), a member of the Class A G protein-coupled receptor superfamily, plays an important role in modulating dopaminergic neuronal activity and eliciting opioid-independent analgesia. Recent studies suggest that promoting \{beta}-arrestin-biased signaling in NTSR1 may diminish drugs of abuse, such as psychostimulants, thereby offering a potential avenue for treating human addiction-related disorders. In this study, we utilized a novel computational and experimental approach that combined nudged elastic band-based molecular dynamics simulations, Markov state models, temporal communication network analysis, site-directed mutagenesis, and conformational biosensors, to explore the intricate mechanisms underlying NTSR1 activation and biased signaling. Our study reveals a dynamic stepwise transition mechanism and activated transmission network associated with NTSR1 activation. It also yields valuable insights into the complex interplay between the unique polar network, non-conserved ion locks, and aromatic clusters in NTSR1 signaling. Moreover, we identified a cryptic allosteric site located in the intracellular region of the receptor that exists in an intermediate state within the activation pathway. Collectively, these findings contribute to a more profound understanding of NTSR1 activation and biased signaling at the atomic level, thereby providing a potential strategy for the development of NTSR1 allosteric modulators in the realm of G protein-coupled receptor biology, biophysics, and medicine.

Exosomes are small vesicles crucial for cell signaling and disease biomarkers. Due to their complexity, an "omics" approach is preferable to individual biomarkers. While Raman spectroscopy is effective for exosome analysis, it requires high sample concentrations and has limited sensitivity to lipids and proteins. Surface-enhanced Raman spectroscopy helps overcome these challenges. In this study, we leverage Neo4j graph databases to organize 3,045 Raman spectra of exosomes, enhancing data generalization. To further refine spectral analysis, we introduce a novel spectral filtering process that integrates the PageRank Filter with optimal Dimensionality Reduction. This method improves feature selection, resulting in superior classification performance. Specifically, the Extra Trees model, using our spectral processing approach, achieves 0.76 and 0.857 accuracy in classifying hyperglycemic, hypoglycemic, and normal exosome samples based on Raman spectra and surface, respectively, with group 10-fold cross-validation. Our results show that graph-based spectral filtering combined with optimal dimensionality reduction significantly improves classification accuracy by reducing noise while preserving key biomarker signals. This novel framework enhances Raman-based exosome analysis, expanding its potential for biomedical applications, disease diagnostics, and biomarker discovery.

Comparing mathematical models offers a means to evaluate competing scientific theories. However, exact methods of model calibration are not applicable to many probabilistic models which simulate high-dimensional spatio-temporal data. Approximate Bayesian Computation is a widely-used method for parameter inference and model selection in such scenarios, and it may be combined with Topological Data Analysis to study models which simulate data with fine spatial structure. We develop a flexible pipeline for parameter inference and model selection in spatio-temporal models. Our pipeline identifies topological summary statistics which quantify spatio-temporal data and uses them to approximate parameter and model posterior distributions. We validate our pipeline on models of tumour-induced angiogenesis, inferring four parameters in three established models and identifying the correct model in synthetic test-cases.

This chapter introduces evolutionary antifragility as the time-scale interaction characteristics of a natural dynamic system. It describes the benefit derived from input distribution unevenness, based on the emergent system dynamics and its uncertain and volatile interactions with the operating environment described by unknown disturbances. We consider methods for the detection, analysis, and modelling of cancer, environmental, microbiota, and social systems antifragility. This is a preprint of the following work Cristia Axenie, Roman Bauer, Oliver Lopez Corona, Jeffrey West, Applied Antifragility in Natural Systems From Principles to Applications, Springer Nature reproduced with the permissions of Springer Nature. The final authenticated version is available online at https://link.springer.com/book/9783031903908

This is the first half of a two-part paper dealing with the geometry of color perception. Here we analyze in detail the seminal 1974 work by H.L. Resnikoff, who showed that there are only two possible geometric structures and Riemannian metrics on the perceived color space P compatible with the set of Schrödinger's axioms completed with the hypothesis of homogeneity. We recast Resnikoff's model into a more modern colorimetric setting, provide a much simpler proof of the main result of the original paper and motivate the need of psychophysical experiments to confute or confirm the linearity of background transformations, which act transitively on P. Finally, we show that the Riemannian metrics singled out by Resnikoff through an axiom on invariance under background transformations are not compatibles with the crispening effect, thus motivating the need of further research about perceptual color metrics.

Functional amyloid fibrils, once primarily associated with amyloidosis, are now recognized for their exceptional potential as biomaterials due to their unique structural features, including remarkable mechanical strength, high stability, and self-assembly capabilities. This review highlights their transformative applications across a wide range of industries, from cutting-edge drug delivery systems and next-generation biosensors to tissue engineering, surface technologies, energy storage, and environmental solutions. Their versatility extends into innovative sectors like information transfer systems, cell adhesion, protein fusion, food technology, and novel catalytic systems. Despite significant progress, critical gaps remain in the research. This review not only consolidates current applications but also underscores the vast potential for future advancements, positioning functional amyloids as key players in emerging biomaterials technologies.

We introduce GenPhylo, a Python module that simulates nucleotide sequence data along a phylogeny avoiding the restriction of continuous-time Markov processes. GenPhylo uses directly a general Markov model and therefore naturally incorporates heterogeneity across lineages. We solve the challenge of generating transition matrices with a pre-given expected number of substitutions (the branch length information) by providing an algorithm that can be incorporated in other simulation software.

This paper studies subtypes of restricted, repetitive and stereotypical behaviors (RRBs) in adolescent males with autism spectrum disorder (ASD) from the viewpoint of the dynamics of brain functional connectivities (FCs). Data from the ABIDE-II repository and Repetitive Behavior Scale-Revised (RBS-R) metrics are used to form two ASD groups with tightly controlled demographics; one comprises subjects with scores above threshold for the self-injurious behaviors (SIBs) subscale, and the other subjects with scores below threshold for SIBs, but above threshold for at least one of the other subscales (stereotyped, compulsive, ritualistic, insistence on sameness, restricted interests). The dynamics of the coherence for FCs across distinct frequency bands are compared against matched controls, using a novel volatility measure computed in time-frequency space. We find statistically significant differences, on average, in the volatility of a relatively small set of FCs, most mapping to either the default mode network or the cerebellum, in the mid- and high-frequency bands, and yielding higher volatility in subjects with high levels of SIBs. Results suggest a distinct underlying profile for SIBs involving multiple brain regions associated with rewards and emotions processing. The work contributes to the identification of neural substrates potentially underlying behavioral subtypes, and may help target interventions.

Weak magnetic fields and isotopes have been shown to influence biological processes; however, the underlying mechanisms remain poorly understood, particularly because the corresponding interaction energies are far below thermal energies, making classical explanations challenging or impossible. Microtubules, dynamic cytoskeletal fibers, offer an ideal system to test weak magnetic field effects due to their self-assembling capabilities, sensitivity to magnetic fields, and their central role in cellular processes. In this study, we use a combination of experiments and simulations to explore how nuclear spin dynamics affect microtubule polymerization by examining interactions between magnesium isotope substitution and weak magnetic fields. Our experiments reveal an isotope-dependent effect, which can be explained via a radical pair mechanism, explicitly arising from nuclear spin properties rather than isotopic mass differences. This nuclear spin-driven isotope effect is notably enhanced under an applied weak magnetic field of approximately 3 mT. Our theoretical model based on radical pairs achieves quantitative agreement with our experimental observations. These results establish a direct connection between quantum spin dynamics and microtubule assembly, providing new insights into how weak magnetic fields influence cellular and biomolecular functions.

Standardized performance evaluation of fluorescence imaging systems remains a critical unmet need in the field of fluorescence-guided surgery (FGS). While the American Association of Physicists in Medicine (AAPM) TG311 report and recent FDA draft guidance provide recommended metrics for system characterization, practical tools for extracting these metrics remain limited, inconsistent, and often inaccessible. We present QUEL-QAL, an open-source Python library designed to streamline and standardize the quantitative analysis of fluorescence images using solid reference targets. The library provides a modular, reproducible workflow that includes region of interest (ROI) detection, statistical analysis, and visualization capabilities. QUEL-QAL supports key metrics such as response linearity, limit of detection, depth sensitivity, and spatial resolution, in alignment with regulatory and academic guidance. Built on widely adopted Python packages, the library is designed to be extensible, enabling users to adapt it to novel target designs and analysis protocols. By promoting transparency, reproducibility, and regulatory alignment, QUEL-QAL offers a foundational tool to support standardized benchmarking and accelerate the development and evaluation of fluorescence imaging systems.

Typology is a subfield of linguistics that focuses on the study and classification of languages based on their structural features. Unlike genealogical classification, which examines the historical relationships between languages, typology seeks to understand the diversity of human languages by identifying common properties and patterns, known as universals. In recent years, computational methods have played an increasingly important role in typological research, enabling the analysis of large-scale linguistic data and the testing of hypotheses about language structure and evolution. This article provides an illustration of the benefits of computational statistical modeling in typology.