PLoS Computational Biology最新文献

{"title":"Identification of letters distorted by physiologically-inspired spatial scrambling.","authors":"Raffles Xingqi Zhu, Alex S Baldwin","doi":"10.1371/journal.pcbi.1014856","DOIUrl":"10.1371/journal.pcbi.1014856","url":null,"abstract":"<p><p>In the geniculostriate pathway of the human visual system, neuronal projections carry signals from a particular retinal locus in parallel from one anatomical area to the next. Imprecision in the fidelity of these projections would place constraints on the ability of the system to perform tasks requiring positional information. We investigated the impact that \"spatial scrambling\" between stages would have on visual performance. We consider two stages in a simple canonical model of the early visual cortex where scrambling might occur: either the input to the first orientation-tuned mechanisms (analogous to V1 simple cells), or the output from those mechanisms. These are referred as \"subcortical\" (SCS) and \"cortical scrambling\" (CS). We developed a wavelet decomposition and resynthesis algorithm to mimic these effects, and measured human performance in letter identification affected by the two types of scrambling. Our results showed SCS and CS have distinguishable effects on both perceived noisiness of letters and letter identification threshold. Comparing human performance against a suite of pre-trained and custom convolutional neural networks (CNNs) that were trained on the scrambled stimuli, relative efficiency (calculated from the ratio of human:CNN thresholds) is higher for CS than SCS. However, in modelling human inefficiency by reducing the proportion of wavelets available to the CNNs, humans are less efficient in CS than SCS. These differences in efficiencies show humans are better at processing orientation redundant stimuli (CS) than orientation noisy stimuli (SCS). We hypothesize this reflects differences in integration properties at the input and output stages of simple cells in the cortex.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014856"},"PeriodicalIF":3.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.","authors":"Marta Sánchez-Carbonell, Sonia Bolshakova, Juan E Ávila-Pagán, Yaseer A Sabir, Clay Griffin-Derr, Dominik G Stich, Sofia V Cieslewicz, Sheyla Esther Carmen Sifuentes, Rhushikesh A Phadke, Alison Brack, Anna Hasche-Kluender, Paige Caley, Caroline Dias, Alberto Cruz-Martín","doi":"10.1371/journal.pcbi.1014871","DOIUrl":"10.1371/journal.pcbi.1014871","url":null,"abstract":"<p><p>The complement component C4 regulates synaptic refinement and plasticity in the brain and has been implicated in multiple neurological and psychiatric disorders, with especially strong genetic evidence linking elevated C4A expression to schizophrenia. However, it remains unclear whether localized C4 elevation in a small neuronal population is sufficient to reshape broader cortical gene-regulatory programs and cellular phenotypes. To address this question, we overexpressed mouse C4 in approximately 2% of prefrontal cortical neurons using in utero electroporation and performed bulk RNA sequencing on microdissected prefrontal cortex. Despite the sparse manipulation, C4-OE was associated with broad transcriptional remodeling across tissue composed predominantly of untransfected cells, including coordinated changes in cholesterol biosynthesis, axon- and synaptic-associated programs, vascular/ECM pathways, and immune- and stress-related responses. Comparison with a schizophrenia synaptic proteomic dataset identified limited global correspondence but selective gene- and pathway-level overlap in specific molecular programs. Reference-based projection of directional DEG signatures onto a cortical single-cell transcriptomic reference further identified cell-type-associated structure, including prominent astrocyte- and vascular-associated axes and distinct lipid/metabolic, vascular/endothelial-interferon-associated, and immune/stress correlation domains. Spatial validation with MFISH showed increased Hmgcr expression in neighboring GFP-negative cells, while PLIN2 imaging revealed increased DAPI-associated/perinuclear lipid-droplet burden within the local C4-OE field. Together, these findings support a model in which sparse neuronal C4 elevation is associated with broader remodeling of the local cortical environment, including a non-cell-autonomous component involving neighboring-cell lipid-associated responses. These results expand the interpretation of C4 risk biology beyond synapse elimination alone and suggest that focal immune-gene dysregulation can engage lipid-homeostatic, stress-related, and cell-type-associated transcriptional programs relevant to cortical circuit vulnerability.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014871"},"PeriodicalIF":3.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latent encoding of movement in primary visual cortex.","authors":"Hannah Germaine, Isaiah Choi, Stephen D Van Hooser, Jérôme Ribot, Jonathan David Touboul","doi":"10.1371/journal.pcbi.1014826","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1014826","url":null,"abstract":"<p><p>Neurons in the primary visual cortex (V1) are classically thought to encode spatial features of visual stimuli through simple population codes: each neuron exhibits a preferred orientation and preferred spatial frequency, both of which remaining invariant to other aspects of the visual stimulus. Here, we show that this simple rule does not apply to the representation of major features of stimulus motion, including stimulus direction and temporal frequency (TF). We collected an extensive dataset of cat V1 responses to stimuli covarying in orientation, direction, spatial frequency, and TF to assess the extent of motion selectivity. We show that preferred TF is mostly uniform across the cortical surface. Yet, in over half of V1, the preferred direction is reversed with changing stimulus TF, revealing four distinct map motifs embedded in V1's functional architecture. Similarly, despite the lack of spatial modulation for the preferred TF map and the lack of invariance for the preferred direction map, we found using convolutional neural networks that direction, TF and stimulus speed can be accurately decoded from V1 responses at all cortical locations. These findings suggest a latent encoding of information where subtle, spatially distributed modulations of V1 activity may convey fine information about stimulus motion, pointing to a novel primary sensory encoding mechanism despite complex co-variation of responses to multiple attributes across V1 neurons.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014826"},"PeriodicalIF":3.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding cell fate decisions with temporal attention.","authors":"Florian Bürger, Martim Dias Gomes, Adrián E Granada, Noémie Moreau, Katarzyna Bozek","doi":"10.1371/journal.pcbi.1014813","DOIUrl":"10.1371/journal.pcbi.1014813","url":null,"abstract":"<p><p>Understanding non-genetic determinants of cell fate is critical for developing and improving cancer therapies, as genetically identical cells can exhibit divergent outcomes under the same treatment conditions. In this work, we present a deep learning approach for cell fate prediction from raw long-term live-cell recordings of cancer cell populations under chemotherapeutic treatment. Our Transformer model is trained to predict cell fate directly from raw image sequences, without relying on predefined morphological or molecular features. Beyond classification, we introduce a comprehensive explainability framework for interpreting the temporal and morphological cues guiding the model's predictions. We demonstrate that prediction of cell outcomes is possible based on the video only, our model achieves balanced accuracy of 0.94 and an F1-score of 0.93. Attention and masking experiments further indicate that the signal predictive of the cell fate is not uniquely located in the final frames of a cell trajectory, as reliable predictions are possible up to 8 h before the event. Our analysis reveals distinct temporal distribution of predictive information in the mitotic and apoptotic sequences, as well as the role of cell morphology and p53 signaling in determining cell outcomes. Together, these findings demonstrate that attention-based temporal models enable accurate cell fate prediction while providing biologically interpretable insights into non-genetic determinants of cellular decision-making.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014813"},"PeriodicalIF":3.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimony 3: Extending human-readable model definitions for SBML Level 3 Core and Packages.","authors":"Adel Heydarabadipour, Lucian P Smith, Joseph L Hellerstein, Herbert M Sauro","doi":"10.1371/journal.pcbi.1014207","DOIUrl":"10.1371/journal.pcbi.1014207","url":null,"abstract":"<p><p>Antimony is a human-readable language for defining and sharing models developed by the systems biology community. It enables scientists to describe biochemical networks with a simple syntax, while supporting seamless conversion to and from the Systems Biology Markup Language (SBML) community standard. Since Antimony's original release, both SBML and modeling practices have evolved significantly, creating a need to update Antimony to maintain its standards compliance and practical relevance. In this paper, we introduce Antimony 3, a comprehensive update that formalizes its cumulative improvements and extends its support for SBML Level 3 Core and Flux Balance Constraints (FBC), Distributions, Layout, and Render packages. Antimony 3 enables model specifications that combine kinetic reactions with flux balance analysis, represent uncertainty using probability distributions, add biological context through annotations, and define publication-ready visualizations, all within a unified plain-text format. Antimony 3 is delivered as a lightweight C/C++ library with a stable C API. It is available through official bindings for Python, Julia, and JavaScript/WebAssembly, as well as a cross-platform desktop GUI, which enables straightforward use across scripting environments, desktop applications, and browser-based tools. Antimony 3 is released as open-source software under the BSD 3-Clause License and is available at https://github.com/sys-bio/antimony.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014207"},"PeriodicalIF":3.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic workforce modulation and foraging efficiency in Eusocial insect colonies.","authors":"Daniel Campos, Javier Cristín, Pol Fernández-López, Roger Lloret-Cabot, Meritxell Genovart, Frederic Bartumeus","doi":"10.1371/journal.pcbi.1014258","DOIUrl":"10.1371/journal.pcbi.1014258","url":null,"abstract":"<p><p>Understanding the fitness advantages conferred by eusociality remains a central challenge in behavioral ecology. One promising approach is to identify collective strategies that shift efficiency within social groups. Here, we explore the hypothesis that reserve workforces in ant colonies represent an adaptive mechanism that enhances flexibility and foraging efficiency under fluctuating environmental conditions. We examine how departure and return rates of foragers modulate such reserve workers and how these time-dependent dynamics shape the colony's overall energetic balance. By integrating an energetic-balance framework with stochastic search simulations inspired by empirical results from four colonies of Aphaenogaster senilis ants, we quantify the energetic requirements for colony viability, incorporating energy intake, search costs, and basal metabolic demands. Our results show that as colonies grow, maintaining a positive energy balance requires a disproportionately larger relative workforce. By modulating departure and return rates over time, colonies control the synchrony of their collective search and efficiently activate or suppress their reserve workforce to scale foraging effort as needed. These findings suggest that the \"lazy\" or weakly engaged workers commonly observed in large colonies function as an essential reserve that stabilizes colony energetics and enhances responsiveness. Together, our results provide a functional explanation for sublinear metabolic scaling in eusocial groups and highlight workforce modulation as a key factor underlying their energetic stability and evolutionary success.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014258"},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A statistical damage model for coupled mechano-electrophysiological axonal injury.","authors":"Zexuan Chen, Liqun Tang, Bao Yang, Yiping Liu, Zhenyu Jiang, Licheng Zhou, Zejia Liu","doi":"10.1371/journal.pcbi.1014837","DOIUrl":"10.1371/journal.pcbi.1014837","url":null,"abstract":"<p><p>Deformation-induced injury of white matter nerve bundles is prevalent in central nervous system injuries, leading to a series of neurological dysfunctions. To describe the effect of deformation injury on the physiological electrical signals of neurons, several axonal electrophysiological damage models based on the Hodgkin-Huxley equations have been proposed. However, none of these models can fully characterize the results of white matter nerve stretching experiments under different rates and amplitudes. Building on previous work by peers, we propose a novel axonal deformation damage model that comprehensively considers the coupled effects of sodium and potassium channel damage on gating variable rate constants, as well as the differences in mechanical properties and injury among individual axons during deformation-with these differences continuously modeled by a statistical distribution. The proposed model can not only reasonably describe the sodium left-shift phenomenon (a key post-injury feature) but also accurately reproduce the neuro-electrophysiological responses of nerve fascicles under various stretching conditions. This new neuro-electrophysiological model for nerve fascicle injury exhibits good universality and provides a mechanical mechanism-based reference for future clinical treatment strategies of nerve injury.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014837"},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Process bigraphs and the architecture of compositional systems biology.","authors":"Eran Agmon, Ryan K Spangler","doi":"10.1371/journal.pcbi.1014819","DOIUrl":"10.1371/journal.pcbi.1014819","url":null,"abstract":"<p><p>Building multiscale biological models requires the integration of independently developed submodels, which means moving shared variables between them and coordinating when each submodel runs. Existing tools typically address isolated biological mechanisms with specific numerical methods, rarely specify which variables each model reads and writes, how those variables are translated, and how model updates are synchronized. We present Process Bigraph, a framework for composing and simulating multiscale models. Process Bigraph generalizes the architectural ideas previously used in the Vivarium software into a shared specification that describes process interfaces, hierarchical data structures, composition patterns, and orchestration patterns. The paper explains how the framework is organized and why it makes biological models easier to understand, reuse, and build on; S1 Text provides the formal specification. We introduce Vivarium 2.0 as an open-source implementation of the process bigraph framework. We demonstrate its utility with Spatio-Flux, a standalone library of microbial ecosystem simulations that combine kinetic equations, dynamic flux balance analysis, and different spatial processes. These simulations illustrated how the framework effectively integrates diverse biological processes, leading to emergent spatially organized population dynamics. Finally, we discuss implications for emerging multiscale modeling standards. Availability and implementation: Vivarium 2.0 is a suite of software libraries that include: (1) bigraph-schema, for defining and operating on data types within a hierarchical JSON-based format; (2) process-bigraph, for defining process interfaces, composite simulations, and executing them; and (3) viva-superpowers, for AI-assisted construction and composition of process bigraphs. Spatio-Flux is a reference application used in this paper to demonstrate the framework's utility. S1 Text provides detailed descriptions of these software libraries. All software is open-source and available at: https://github.com/vivarium-collective.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014819"},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyper-mutational processes provide a head-start for weak cancer drivers: Explaining atypical KRAS variants.","authors":"Michael D Nicholson, Ian Tomlinson","doi":"10.1371/journal.pcbi.1014858","DOIUrl":"10.1371/journal.pcbi.1014858","url":null,"abstract":"<p><p>Hypermutant cancers frequently contain atypical driver gene variants, which may provide sub-optimal oncogenic advantages. The reason why weak cancer drivers prevail and are not outcompeted by stronger alternatives is unclear. Here, using mathematical modelling, we show that aberrant mutational processes alone can account for the detection of weak, rather than canonical, driver mutations. We find that simply increasing the mutation rate per cell division, without altering selection or mutational biases, can lead to the dominance of weak drivers due to rapidly occurring further driver events. This effect can be further enhanced by mutational biases towards specific nucleotide sequence contexts. Focusing on POLE-mutant (DNA polymerase epsilon proofreading-deficient) colorectal cancers, we quantify the mutation bias for varied KRAS drivers under both POLE-mutant and non-hypermutant mutational processes. In POLE-mutant cancers, the combination of the bias coupled with an elevated mutation rate is sufficient to explain the enrichment of atypical KRAS drivers. Furthermore, model predictions are consistent with the observed prevalence of atypical KRAS drivers observed in mismatch repair deficient colorectal cancers. Thus, differential selection across these cancer types need not be invoked to explain the variation in driver mutations. Our study clarifies the interplay of mutation and selection during the evolutionary dynamics of tumourigenesis.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014858"},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How does explicit reliability guide choices? Effect of trustworthiness on choice and metacognition.","authors":"Keiji Ota, Anthony Ciston, Patrick Haggard, Thibault Gajdos Preuss, Lucie Charles","doi":"10.1371/journal.pcbi.1014818","DOIUrl":"10.1371/journal.pcbi.1014818","url":null,"abstract":"<p><p>A key challenge in today's fast-paced digital world is to integrate information from various sources, which differ in their reliability. Yet, little is known about how explicit probabilistic information about the likelihood that a source provides correct information is used in decision-making. Here, we investigated how such explicit reliability markers are integrated into decisions and the extent to which individuals have metacognitive insight into this process. We developed a novel paradigm where participants viewed predictions from sources of varying explicit reliability to help them make a choice between two options. After each decision, they rated how much they felt a given source influenced their choice. Using computational modelling, we estimated the effective reliability that participants assigned to each source. Overall, we found that participants did not take source reliability at face value, inappropriately using the stated probabilities of source correctness to make a choice. Interestingly, even sources that were explicitly labelled as unreliable biased choices, as if these were treated as moderately reliable. Additionally, the presence of sources flagged as lying ones and known to be reliably predicting the incorrect answer impaired performance by increasing leakiness in evidence accumulation. Despite these biases, participants showed some metacognitive awareness of what influenced their choices: they were aware of the impact unreliable sources had on their decisions and could evaluate how much a given source had increased the likelihood of their response. These results suggest that people distort explicit source reliability but have some awareness of this process.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"22 10","pages":"e1014818"},"PeriodicalIF":3.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}