PLoS Computational Biology最新文献

{"title":"Capturing continuous, long timescale behavioral changes in Drosophila melanogaster postural data.","authors":"Grace C McKenzie-Smith, Scott W Wolf, Julien F Ayroles, Joshua W Shaevitz","doi":"10.1371/journal.pcbi.1012753","DOIUrl":"10.1371/journal.pcbi.1012753","url":null,"abstract":"<p><p>Animal behavior spans many timescales, from short, seconds-scale actions to daily rhythms over many hours to life-long changes during aging. To access longer timescales of behavior, we continuously recorded individual Drosophila melanogaster at 100 frames per second for up to 7 days at a time in featureless arenas on sucrose-agarose media. We use the deep learning framework SLEAP to produce a full-body postural dataset for 47 individuals resulting in nearly 2 billion pose instances. We identify stereotyped behaviors such as grooming, proboscis extension, and locomotion and use the resulting ethograms to explore how the flies' behavior varies across time of day and days in the experiment. We find distinct daily patterns in all stereotyped behaviors, adding specific information about trends in different grooming modalities, proboscis extension duration, and locomotion speed to what is known about the D. melanogaster circadian cycle. Using our holistic measurements of behavior, we find that the hour after dawn is a unique time point in the flies' daily pattern of behavior, and that the behavioral composition of this hour tracks well with other indicators of health such as locomotion speed and the fraction of time spend moving vs. resting. The method, data, and analysis presented here give us a new and clearer picture of D. melanogaster behavior across timescales, revealing novel features that hint at unexplored underlying biological mechanisms.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 2","pages":"e1012753"},"PeriodicalIF":3.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123431","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":"Simulation-based validation of a method to detect changes in SARS-CoV-2 reinfection risk.","authors":"Belinda Lombard, Harry Moultrie, Juliet R C Pulliam, Cari van Schalkwyk","doi":"10.1371/journal.pcbi.1012792","DOIUrl":"10.1371/journal.pcbi.1012792","url":null,"abstract":"<p><p>Given the high global seroprevalence of SARS-CoV-2, understanding the risk of reinfection has become increasingly important. Models developed to track trends in reinfection risk should be robust against possible biases arising from imperfect data observation processes. We performed simulation-based validation of an existing catalytic model designed to detect changes in the risk of reinfection by SARS-CoV-2. The catalytic model assumes the risk of reinfection is proportional to observed infections. Validation involved using simulated primary infections, consistent with the number of observed infections in South Africa. To assess the performance of the catalytic model, we simulated reinfection datasets that incorporated different processes that may bias inference, including imperfect observation and mortality. A Bayesian approach was used to fit the model to simulated data, assuming a negative binomial distribution around the expected number of reinfections, and model projections were compared to the simulated data using different magnitudes of change in reinfection risk. We assessed the model's ability to accurately detect changes in reinfection risk when included in the simulations, as well as the occurrence of false positives when reinfection risk remained constant. The model parameters converged in most scenarios leading to model outputs aligning with anticipated outcomes. The model successfully detected changes in the risk of reinfection when such a change was introduced to the data. Low observation probabilities (10%) of both primary- and reinfections resulted in low numbers of observed cases from the simulated data and poor convergence. The model's performance was assessed on simulated data representative of the South African SARS-CoV-2 epidemic, reflecting its timing of waves and outbreak magnitude. Model performance under similar scenarios may be different in settings with smaller epidemics (and therefore smaller numbers of reinfections). Ensuring model parameter convergence is essential to avoid false-positive detection of shifts in reinfection risk. While the model is robust in most scenarios of imperfect observation and mortality, further simulation-based validation for regions experiencing smaller outbreaks is recommended. Caution must be exercised in directly extrapolating results across different epidemiological contexts without additional validation efforts.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 2","pages":"e1012792"},"PeriodicalIF":3.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123440","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":"RSero: A user-friendly R package to reconstruct pathogen circulation history from seroprevalence studies.","authors":"Nathanaël Hozé, Margarita Pons-Salort, C Jessica E Metcalf, Michael White, Henrik Salje, Simon Cauchemez","doi":"10.1371/journal.pcbi.1012777","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012777","url":null,"abstract":"<p><p>Population-based serological surveys are a key tool in epidemiology to characterize the level of population immunity and reconstruct the past circulation of pathogens. A variety of serocatalytic models have been developed to estimate the force of infection (FOI) (i.e., the rate at which susceptible individuals become infected) from age-stratified seroprevalence data. However, few tool currently exists to easily implement, combine, and compare these models. Here, we introduce an R package, Rsero, that implements a series of serocatalytic models and estimates the FOI from age-stratified seroprevalence data using Bayesian methods. The package also contains a series of features to perform model comparison and visualise model fit. We introduce new serocatalytic models of successive outbreaks and extend existing models of seroreversion to any transmission model. The different features of the package are illustrated with simulated and real-life data. We show we can identify the correct epidemiological scenario and recover model parameters in different epidemiological settings. We also show how the package can support serosurvey study design in a variety of epidemic situations. This package provides a standard framework to epidemiologists and modellers to study the dynamics of past pathogen circulation from cross-sectional serological survey data.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 2","pages":"e1012777"},"PeriodicalIF":3.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123437","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":"Design of field trials for the evaluation of transmissible vaccines in animal populations.","authors":"Justin K Sheen, Lee Kennedy-Shaffer, Michael Z Levy, Charlotte Jessica E Metcalf","doi":"10.1371/journal.pcbi.1012779","DOIUrl":"10.1371/journal.pcbi.1012779","url":null,"abstract":"<p><p>Vaccines which can transmit from vaccinated to unvaccinated animals may be especially useful for increasing immunity in hard to reach populations or in populations where achieving high coverage is logistically infeasible. However, gauging the public health utility for future use of such transmissible vaccines and assessing their risk-benefit tradeoff, given their potential for unintended evolution, hinges on accurate estimates of their indirect protective effect. Here, we establish the conditions under which a two-stage randomized field trial can characterize the protective effects of a transmissible vaccine relative to a traditional vaccine. We contrast the sample sizes required to adequately power these trials when the vaccine is weakly and strongly transmissible. We also identify how required sample sizes change based on the characteristics of host ecology such as the overdispersion of the contact structure of the population, as well as the efficacy of the vaccine and timing of vaccination. Our results indicate the range of scenarios where two-stage randomized field trial designs are feasible and appropriate to capture the protective effects of transmissible vaccines. Our estimates identify the protective benefit of using transmissible vaccines compared to traditional vaccines, and thus can be used to weigh against evolutionary risks.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 2","pages":"e1012779"},"PeriodicalIF":3.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123435","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":"Bayesian identification of differentially expressed isoforms using a novel joint model of RNA-seq data.","authors":"Xu Shi, Xiao Wang, Lu Jin, Leena Halakivi-Clarke, Robert Clarke, Andrew F Neuwald, Jianhua Xuan","doi":"10.1371/journal.pcbi.1012750","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012750","url":null,"abstract":"<p><p>We develop a Bayesian approach, BayesIso, to identify differentially expressed isoforms from RNA-seq data. The approach features a novel joint model of the sample variability and the deferential state of isoforms. Specifically, the within-sample variability and the between-sample variability of each isoform are modeled by a Poisson-Lognormal model and a Gamma-Gamma model, respectively. Using a Bayesian framework, the differential state of each isoform and the model parameters are jointly estimated by a Markov Chain Monte Carlo (MCMC) method. Extensive studies using simulation and real data demonstrate that BayesIso can effectively detect isoforms of less differentially expressed and differential transcripts for genes with multiple isoforms. We applied the approach to breast cancer RNA-seq data and uncovered a unique set of isoforms that form key pathways associated with breast cancer recurrence. First, PI3K/AKT/mTOR signaling and PTEN signaling pathways are identified as being involved in breast cancer development. Further integrated with protein-protein interaction data, pathways of Jak-STAT, mTOR, MAPK and Wnt signaling are revealed in association with breast cancer recurrence. Finally, several pathways are activated in the early recurrence of breast cancer. In tumors that occur early, members of pathways of cellular metabolism and cell cycle (such as CD36 and TOP2A) are upregulated, while immune response genes such as NFATC1 are downregulated.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012750"},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071232","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":"ASGCL: Adaptive Sparse Mapping-based graph contrastive learning network for cancer drug response prediction.","authors":"Yunyun Dong, Yuanrong Zhang, Yuhua Qian, Yiming Zhao, Ziting Yang, Xiufang Feng","doi":"10.1371/journal.pcbi.1012748","DOIUrl":"10.1371/journal.pcbi.1012748","url":null,"abstract":"<p><p>Personalized cancer drug treatment is emerging as a frontier issue in modern medical research. Considering the genomic differences among cancer patients, determining the most effective drug treatment plan is a complex and crucial task. In response to these challenges, this study introduces the Adaptive Sparse Graph Contrastive Learning Network (ASGCL), an innovative approach to unraveling latent interactions in the complex context of cancer cell lines and drugs. The core of ASGCL is the GraphMorpher module, an innovative component that enhances the input graph structure via strategic node attribute masking and topological pruning. By contrasting the augmented graph with the original input, the model delineates distinct positive and negative sample sets at both node and graph levels. This dual-level contrastive approach significantly amplifies the model's discriminatory prowess in identifying nuanced drug responses. Leveraging a synergistic combination of supervised and contrastive loss, ASGCL accomplishes end-to-end learning of feature representations, substantially outperforming existing methodologies. Comprehensive ablation studies underscore the efficacy of each component, corroborating the model's robustness. Experimental evaluations further illuminate ASGCL's proficiency in predicting drug responses, offering a potent tool for guiding clinical decision-making in cancer therapy.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012748"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067498","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":"The role of oscillations in grid cells' toroidal topology.","authors":"Giovanni di Sarra, Siddharth Jha, Yasser Roudi","doi":"10.1371/journal.pcbi.1012776","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012776","url":null,"abstract":"<p><p>Persistent homology applied to the activity of grid cells in the Medial Entorhinal Cortex suggests that this activity lies on a toroidal manifold. By analyzing real data and a simple model, we show that neural oscillations play a key role in the appearance of this toroidal topology. To quantitatively monitor how changes in spike trains influence the topology of the data, we first define a robust measure for the degree of toroidality of a dataset. Using this measure, we find that small perturbations ( ~ 100 ms) of spike times have little influence on both the toroidality and the hexagonality of the ratemaps. Jittering spikes by  ~ 100-500 ms, however, destroys the toroidal topology, while still having little impact on grid scores. These critical jittering time scales fall in the range of the periods of oscillations between the theta and eta bands. We thus hypothesized that these oscillatory modulations of neuronal spiking play a key role in the appearance and robustness of toroidal topology and the hexagonal spatial selectivity is not sufficient. We confirmed this hypothesis using a simple model for the activity of grid cells, consisting of an ensemble of independent rate-modulated Poisson processes. When these rates were modulated by oscillations, the network behaved similarly to the real data in exhibiting toroidal topology, even when the position of the fields were perturbed. In the absence of oscillations, this similarity was substantially lower. Furthermore, we find that the experimentally recorded spike trains indeed exhibit temporal modulations at the eta and theta bands, and that the ratio of the power in the eta band to that of the theta band, [Formula: see text], correlates with the critical jittering time at which the toroidal topology disappears.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012776"},"PeriodicalIF":3.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067524","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":"The calcitron: A simple neuron model that implements many learning rules via the calcium control hypothesis.","authors":"Toviah Moldwin, Li Shay Azran, Idan Segev","doi":"10.1371/journal.pcbi.1012754","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012754","url":null,"abstract":"<p><p>Theoretical neuroscientists and machine learning researchers have proposed a variety of learning rules to enable artificial neural networks to effectively perform both supervised and unsupervised learning tasks. It is not always clear, however, how these theoretically-derived rules relate to biological mechanisms of plasticity in the brain, or how these different rules might be mechanistically implemented in different contexts and brain regions. This study shows that the calcium control hypothesis, which relates synaptic plasticity in the brain to the calcium concentration ([Ca2+]) in dendritic spines, can produce a diverse array of learning rules. We propose a simple, perceptron-like neuron model that has four sources of [Ca2+]: local (following the activation of an excitatory synapse and confined to that synapse), heterosynaptic (resulting from the activity of other synapses), postsynaptic spike-dependent, and supervisor-dependent. We demonstrate that by modulating the plasticity thresholds and calcium influx from each calcium source, we can reproduce a wide range of learning and plasticity protocols, such as Hebbian and anti-Hebbian learning, frequency-dependent plasticity, and unsupervised recognition of frequently repeating input patterns. Moreover, by devising simple neural circuits to provide supervisory signals, we show how the calcitron can implement homeostatic plasticity, perceptron learning, and BTSP-inspired one-shot learning. Our study bridges the gap between theoretical learning algorithms and their biological counterparts, not only replicating established learning paradigms but also introducing novel rules.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012754"},"PeriodicalIF":3.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067520","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":"Spherical harmonics texture extraction for versatile analysis of biological objects.","authors":"Oane Gros, Josiah B Passmore, Noa O Borst, Dominik Kutra, Wilco Nijenhuis, Timothy Fuqua, Lukas C Kapitein, Justin M Crocker, Anna Kreshuk, Simone Köhler","doi":"10.1371/journal.pcbi.1012349","DOIUrl":"10.1371/journal.pcbi.1012349","url":null,"abstract":"<p><p>The characterization of phenotypes in cells or organisms from microscopy data largely depends on differences in the spatial distribution of image intensity. Multiple methods exist for quantifying the intensity distribution - or image texture - across objects in natural images. However, many of these texture extraction methods do not directly adapt to 3D microscopy data. Here, we present Spherical Texture extraction, which measures the variance in intensity per angular wavelength by calculating the Spherical Harmonics or Fourier power spectrum of a spherical or circular projection of the angular mean intensity of the object. This method provides a 20-value characterization that quantifies the scale of features in the spherical projection of the intensity distribution, giving a different signal if the intensity is, for example, clustered in parts of the volume or spread across the entire volume. We apply this method to different systems and demonstrate its ability to describe various biological problems through feature extraction. The Spherical Texture extraction characterizes biologically defined gene expression patterns in Drosophila melanogaster embryos, giving a quantitative read-out for pattern formation. Our method can also quantify morphological differences in Caenorhabditis elegans germline nuclei, which lack a predefined pattern. We show that the classification of germline nuclei using their Spherical Texture outperforms a convolutional neural net when training data is limited. Additionally, we use a similar pipeline on 2D cell migration data to extract the polarization direction and quantify the alignment of fluorescent markers to the migration direction. We implemented the Spherical Texture method as a plugin in ilastik to provide a parameter-free and data-agnostic application to any segmented 3D or 2D dataset. Additionally, this technique can also be applied through a Python package to provide extra feature extraction for any object classification pipeline or downstream analysis.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012349"},"PeriodicalIF":3.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067517","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":"Correction: Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation.","authors":"Phoebe Asplin, Matt J Keeling, Rebecca Mancy, Edward M Hill","doi":"10.1371/journal.pcbi.1012791","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012791","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pcbi.1012096.].</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"21 1","pages":"e1012791"},"PeriodicalIF":3.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067501","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}