PLoS Computational Biology最新文献

{"title":"Predicting the infecting dengue serotype from antibody titre data using machine learning.","authors":"Bethan Cracknell Daniels, Darunee Buddhari, Taweewun Hunsawong, Sopon Iamsirithaworn, Aaron R Farmer, Derek A T Cummings, Kathryn B Anderson, Ilaria Dorigatti","doi":"10.1371/journal.pcbi.1012188","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012188","url":null,"abstract":"<p><p>The development of a safe and efficacious vaccine that provides immunity against all four dengue virus serotypes is a priority, and a significant challenge for vaccine development has been defining and measuring serotype-specific outcomes and correlates of protection. The plaque reduction neutralisation test (PRNT) is the gold standard assay for measuring serotype-specific antibodies, but this test cannot differentiate homotypic and heterotypic antibodies and characterising the infection history is challenging. To address this, we present an analysis of pre- and post-infection antibody titres measured using the PRNT, collected from a prospective cohort of Thai children. We applied four machine learning classifiers and multinomial logistic regression to the titre data to predict the infecting serotype. The models were validated against the true infecting serotype, identified using RT-PCR. Model performance was calculated using 100 bootstrap samples of the train and out-of-sample test sets. Our analysis showed that, on average, the greatest change in titre was against the infecting serotype. However, in 53.4% (109/204) of the subjects, the highest titre change did not correspond to the infecting serotype, including in 34.3% (11/35) of dengue-naïve individuals (although 8/11 of these seronegative individuals were seropositive to Japanese encephalitis virus prior to their infection). The highest post-infection titres of seropositive cases were more likely to match the serotype of the highest pre-infection titre than the infecting serotype, consistent with antigenic seniority or cross-reactive boosting of pre-infection titres. Despite these challenges, the best performing machine learning algorithm achieved 76.3% (95% CI 57.9-89.5%) accuracy on the out-of-sample test set in predicting the infecting serotype from PRNT data. Incorporating additional spatiotemporal data improved accuracy to 80.6% (95% CI 63.2-94.7%), while using only post-infection titres as predictor variables yielded an accuracy of 71.7% (95% CI 57.9-84.2%). These results show that machine learning classifiers can be used to overcome challenges in interpreting PRNT titres, making them useful tools in investigating dengue immune dynamics, infection history and identifying serotype-specific correlates of protection, which in turn can support the evaluation of clinical trial endpoints and vaccine development.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012188"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882656","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":"Evaluation and comparison of methods for neuronal parameter optimization using the Neuroptimus software framework.","authors":"Máté Mohácsi, Márk Patrik Török, Sára Sáray, Luca Tar, Gábor Farkas, Szabolcs Káli","doi":"10.1371/journal.pcbi.1012039","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012039","url":null,"abstract":"<p><p>Finding optimal parameters for detailed neuronal models is a ubiquitous challenge in neuroscientific research. In recent years, manual model tuning has been gradually replaced by automated parameter search using a variety of different tools and methods. However, using most of these software tools and choosing the most appropriate algorithm for a given optimization task require substantial technical expertise, which prevents the majority of researchers from using these methods effectively. To address these issues, we developed a generic platform (called Neuroptimus) that allows users to set up neural parameter optimization tasks via a graphical interface, and to solve these tasks using a wide selection of state-of-the-art parameter search methods implemented by five different Python packages. Neuroptimus also offers several features to support more advanced usage, including the ability to run most algorithms in parallel, which allows it to take advantage of high-performance computing architectures. We used the common interface provided by Neuroptimus to conduct a detailed comparison of more than twenty different algorithms (and implementations) on six distinct benchmarks that represent typical scenarios in neuronal parameter search. We quantified the performance of the algorithms in terms of the best solutions found and in terms of convergence speed. We identified several algorithms, including covariance matrix adaptation evolution strategy and particle swarm optimization, that consistently, without any fine-tuning, found good solutions in all of our use cases. By contrast, some other algorithms including all local search methods provided good solutions only for the simplest use cases, and failed completely on more complex problems. We also demonstrate the versatility of Neuroptimus by applying it to an additional use case that involves tuning the parameters of a subcellular model of biochemical pathways. Finally, we created an online database that allows uploading, querying and analyzing the results of optimization runs performed by Neuroptimus, which enables all researchers to update and extend the current benchmarking study. The tools and analysis we provide should aid members of the neuroscience community to apply parameter search methods more effectively in their research.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012039"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882864","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":"Surveillance for TB drug resistance using routine rapid diagnostic testing data: Methodological development and application in Brazil.","authors":"Sarah E Baum, Daniele M Pelissari, Fernanda Dockhorn Costa, Luiza O Harada, Mauro Sanchez, Patricia Bartholomay, Ted Cohen, Marcia C Castro, Nicolas A Menzies","doi":"10.1371/journal.pcbi.1012662","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012662","url":null,"abstract":"<p><p>Effectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal (i.e. not all patients are offered testing), surveillance for rifampicin-resistance-one of the core drugs in the TB treatment regimen-has relied on resource-intensive and infrequent nationally-representative prevalence surveys. The expanded availability of rapid diagnostic tests (RDTs) over the past decade has increased testing coverage in many settings. However, RDT data collected in the course of routine (but not universal) use may provide biased estimates of resistance if the subset of patients receiving RDTs is not representative of the overall cohort. Here, we developed a method that attempts to correct for non-random use of RDT testing in the context of routine TB diagnosis to recover unbiased estimates of resistance among new and previously treated TB cases. Specifically, we employed statistical corrections to model rifampicin resistance among TB notifications with observed Xpert MTB/RIF (a WHO-recommended RDT) results using a hierarchical generalized additive regression model, and then used model output to impute results for untested individuals. We applied this model to 2017-2023 case-level data on over 800,000 patients from Brazil. Modeled estimates of the prevalence of rifampicin resistance were substantially higher than naïve estimates, with estimated prevalence ranging between 28-44% higher for new cases and 2-17% higher for previously treated cases. Our estimates of RR-TB incidence were estimated with narrower uncertainty intervals relative to WHO estimates for the same time period, and were robust to alternative model specifications. Our approach provides a generalizable method to leverage routine RDT data to derive timely estimates of RR-TB prevalence among notified TB cases in settings where testing for TB drug resistance is not universal.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012662"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882592","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":"A multivalent binding model infers antibody Fc species from systems serology.","authors":"Armaan A Abraham, Zhixin Cyrillus Tan, Priyanka Shrestha, Emily R Bozich, Aaron S Meyer","doi":"10.1371/journal.pcbi.1012663","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012663","url":null,"abstract":"<p><p>Systems serology aims to broadly profile the antigen binding, Fc biophysical features, immune receptor engagement, and effector functions of antibodies. This experimental approach excels at identifying antibody functional features that are relevant to a particular disease. However, a crucial limitation of this approach is its incomplete description of what structural features of the antibodies are responsible for the observed immune receptor engagement and effector functions. Knowing these antibody features is important for both understanding how effector responses are naturally controlled through antibody Fc structure and designing antibody therapies with specific effector profiles. Here, we address this limitation by modeling the molecular interactions occurring in these assays and using this model to infer quantities of specific antibody Fc species among the antibodies being profiled. We used several validation strategies to show that the model accurately infers antibody properties and then applied the model to infer previously unavailable antibody fucosylation information from existing systems serology data. Using this capability, we find that COVID-19 vaccine efficacy is associated with the induction of afucosylated spike protein-targeting IgG. Our results also question an existing assumption that controllers of HIV exhibit gp120-targeting IgG that are less fucosylated than those of progressors. Additionally, we confirm that afucosylated IgG is associated with membrane-associated antigens for COVID-19 and HIV, and present new evidence indicating that this relationship is specific to the host cell membrane. Finally, we use the model to identify redundant assay measurements and subsets of information-rich measurements from which Fc properties can be inferred. In total, our modeling approach provides a quantitative framework for the reasoning typically applied in these studies, improving the ability to draw mechanistic conclusions from these data.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012663"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882825","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":"Estimating the time-varying effective reproduction number via Cycle Threshold-based Transformer.","authors":"Xin-Yu Zhang, Lan-Lan Yu, Wei-Yi Wang, Gui-Quan Sun, Jian-Cheng Lv, Tao Zhou, Quan-Hui Liu","doi":"10.1371/journal.pcbi.1012694","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012694","url":null,"abstract":"<p><p>Monitoring the spread of infectious disease is essential to design and adjust the interventions timely for the prevention of the epidemic outbreak and safeguarding the public health. The governments have generally adopted the incidence-based statistical method to estimate the time-varying effective reproduction number Rt and evaluate the transmission ability of epidemics. However, this method exhibits biases arising from the reported incidence data and assumes the generation interval distribution which is not available at the early stage of epidemic. Recent studies showed that the viral loads characterized by cycle threshold (Ct) of the infected populations evolving throughout the course of epidemic and providing a possibility to infer the epidemic trajectory. In this work, we propose the Cycle Threshold-based Transformer (Ct-Transformer) to estimate Rt. We find the supervised learning of Ct-Transformer outperforms the traditional incidence-based statistic and Ct-based Rt estimating methods, and more importantly Ct-Transformer is robustness to the detection resources. Further, we apply the proposed model to self-supervised pre-training tasks and obtain excellent fine-tuning performance, which attains comparable performance with the supervised Ct-Transformer, verified by both the synthetic and real-world datasets. We demonstrate that the Ct-based deep learning method can improve the real-time estimates of Rt, enabling more easily adapted to the track of the newly emerged epidemic.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012694"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882792","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":"Integration of partially observed multimodal and multiscale neural signals for estimating a neural circuit using dynamic causal modeling.","authors":"Jiyoung Kang, Hae-Jeong Park","doi":"10.1371/journal.pcbi.1012655","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012655","url":null,"abstract":"<p><p>Integrating multiscale, multimodal neuroimaging data is essential for a comprehensive understanding of neural circuits. However, this is challenging due to the inherent trade-offs between spatial coverage and resolution in each modality, necessitating a computational strategy that combines modality-specific information effectively. This study introduces a dynamic causal modeling (DCM) framework designed to address the challenge of combining partially observed, multiscale signals across a larger-scale neural circuit by employing a shared neural state model with modality-specific observation models. The proposed method achieves robust circuit inference by iteratively integrating parameter estimates from local microscale and global meso- or macroscale circuits, derived from signals across various scales and modalities. Parameters estimated from high-resolution data within specific regions inform global circuit estimation by constraining neural properties in unobserved regions, while large-scale circuit data help elucidate detailed local circuitry. Using a virtual ground truth system, we validated the method across diverse experimental settings, combining calcium imaging (CaI), voltage-sensitive dye imaging (VSDI), and blood-oxygen-level-dependent (BOLD) signals-each with distinct coverage and resolution. Our reciprocal and iterative parameter estimation approach markedly improves the accuracy of neural property and connectivity estimates compared to traditional one-step estimation methods. This iterative integration of local and global parameters presents a reliable approach to inferring extensive, complex neural circuits from partially observed, multimodal, and multiscale data, showcasing how information from different scales reciprocally enhances entire circuit parameter estimation.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012655"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882828","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":"Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.","authors":"Kenneth Y Wertheim, Robert Chisholm, Paul Richmond, Dawn Walker","doi":"10.1371/journal.pcbi.1012648","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012648","url":null,"abstract":"<p><p>Neuroblastoma is the most common extra-cranial solid tumour in children. Over half of all high-risk cases are expected to succumb to the disease even after chemotherapy, surgery, and immunotherapy. Although the importance of MYCN amplification in this disease is indisputable, the mechanistic details remain enigmatic. Here, we present a multicellular model of neuroblastoma comprising a continuous automaton, discrete cell agents, and a centre-based mechanical model, as well as the simulation results we obtained with it. The continuous automaton represents the tumour microenvironment as a grid-like structure, where each voxel is associated with continuous variables such as the oxygen level therein. Each discrete cell agent is defined by several attributes, including its cell cycle position, mutations, gene expression pattern, and more with behaviours such as cell cycling and cell death being stochastically dependent on these attributes. The centre-based mechanical model represents the properties of these agents as physical objects, describing how they repel each other as soft spheres. By implementing a stochastic simulation algorithm on modern GPUs, we simulated the dynamics of over one million neuroblastoma cells over a period of months. Specifically, we set up 1200 heterogeneous tumours and tracked the MYCN-amplified clone's dynamics in each, revealed the conditions that favour its growth, and tested its responses to 5000 drug combinations. Our results are in agreement with those reported in the literature and add new insights into how the MYCN-amplified clone's reproductive advantage in a tumour, its gene expression profile, the tumour's other clones (with different mutations), and the tumour's microenvironment are inter-related. Based on the results, we formulated a hypothesis, which argues that there are two distinct populations of neuroblastoma cells in the tumour; the p53 protein is pro-survival in one and pro-apoptosis in the other. It follows that alternating between inhibiting MDM2 to restore p53 activity and inhibiting ARF to attenuate p53 activity is a promising, if unorthodox, therapeutic strategy. The multicellular model has the advantages of modularity, high resolution, and scalability, making it a potential foundation for creating digital twins of neuroblastoma patients.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012648"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882485","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":"Estimating the distribution of parameters in differential equations with repeated cross-sectional data.","authors":"Hyeontae Jo, Sung Woong Cho, Hyung Ju Hwang","doi":"10.1371/journal.pcbi.1012696","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012696","url":null,"abstract":"<p><p>Differential equations are pivotal in modeling and understanding the dynamics of various systems, as they offer insights into their future states through parameter estimation fitted to time series data. In fields such as economy, politics, and biology, the observation data points in the time series are often independently obtained (i.e., Repeated Cross-Sectional (RCS) data). RCS data showed that traditional methods for parameter estimation in differential equations, such as using mean values of RCS data over time, Gaussian Process-based trajectory generation, and Bayesian-based methods, have limitations in estimating the shape of parameter distributions, leading to a significant loss of data information. To address this issue, this study proposes a novel method called Estimation of Parameter Distribution (EPD) that provides accurate distribution of parameters without loss of data information. EPD operates in three main steps: generating synthetic time trajectories by randomly selecting observed values at each time point, estimating parameters of a differential equation that minimizes the discrepancy between these trajectories and the true solution of the equation, and selecting the parameters depending on the scale of discrepancy. We then evaluated the performance of EPD across several models, including exponential growth, logistic population models, and target cell-limited models with delayed virus production, thereby demonstrating the ability of the proposed method in capturing the shape of parameter distributions. Furthermore, we applied EPD to real-world datasets, capturing various shapes of parameter distributions over a normal distribution. These results address the heterogeneity within systems, marking a substantial progression in accurately modeling systems using RCS data. Therefore, EPD marks a significant advancement in accurately modeling systems with RCS data, realizing a deeper understanding of system dynamics and parameter variability.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012696"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882789","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":"Machine learning mathematical models for incidence estimation during pandemics.","authors":"Oscar Fajardo-Fontiveros, Mattia Mattei, Giulio Burgio, Clara Granell, Sergio Gómez, Alex Arenas, Marta Sales-Pardo, Roger Guimerà","doi":"10.1371/journal.pcbi.1012687","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012687","url":null,"abstract":"<p><p>Accurate estimates of the incidence of infectious diseases are key for the control of epidemics. However, healthcare systems are often unable to test the population exhaustively, especially when asymptomatic and paucisymptomatic cases are widespread; this leads to significant and systematic under-reporting of the real incidence. Here, we propose a machine learning approach to estimate the incidence of a pandemic in real-time, using reported cases and the overall test rate. In particular, we use Bayesian symbolic regression to automatically learn the closed-form mathematical models that most parsimoniously describe incidence. We develop and validate our models using COVID-19 incidence values for nine different countries, confirming their ability to accurately predict daily incidence. Remarkably, despite the differences in epidemic trajectories and dynamics across countries, we find that a single model for all countries offers a more parsimonious description and is more predictive of actual incidence compared to separate models for each country. Our results show the potential to accurately model incidence in real-time using closed-form mathematical models, providing a valuable tool for public health decision-makers.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012687"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882359","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":"Extracting interpretable signatures of whole-brain dynamics through systematic comparison.","authors":"Annie G Bryant, Kevin Aquino, Linden Parkes, Alex Fornito, Ben D Fulcher","doi":"10.1371/journal.pcbi.1012692","DOIUrl":"https://doi.org/10.1371/journal.pcbi.1012692","url":null,"abstract":"<p><p>The brain's complex distributed dynamics are typically quantified using a limited set of manually selected statistical properties, leaving the possibility that alternative dynamical properties may outperform those reported for a given application. Here, we address this limitation by systematically comparing diverse, interpretable features of both intra-regional activity and inter-regional functional coupling from resting-state functional magnetic resonance imaging (rs-fMRI) data, demonstrating our method using case-control comparisons of four neuropsychiatric disorders. Our findings generally support the use of linear time-series analysis techniques for rs-fMRI case-control analyses, while also identifying new ways to quantify informative dynamical fMRI structures. While simple statistical representations of fMRI dynamics performed surprisingly well (e.g., properties within a single brain region), combining intra-regional properties with inter-regional coupling generally improved performance, underscoring the distributed, multifaceted changes to fMRI dynamics in neuropsychiatric disorders. The comprehensive, data-driven method introduced here enables systematic identification and interpretation of quantitative dynamical signatures of multivariate time-series data, with applicability beyond neuroimaging to diverse scientific problems involving complex time-varying systems.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 12","pages":"e1012692"},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882814","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}