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Deterministic modelling of asymptomatic spread and disease stage progression in vaccine preventable infectious diseases 疫苗可预防传染病中无症状传播和疾病阶段进展的确定性建模
Pub Date : 2024-07-14 DOI: 10.1002/qub2.50
Gabor Kiss, S. Moutari, Cara Mctaggart, Lynsey Patterson, Frank Kee, Felicity Lamrock
This study introduces a deterministic formulation for modelling the asymptotic spread of a vaccine preventable disease as well as the different stages for the progression of the disease. We derive the formula for the associated basic reproduction number. To illustrate the proposed model, we use data from the 2017–2018 diphtheria outbreak in Yemen and fit the parameters of the model. A sensitivity analysis of the basic reproduction number, with respect to the model parameters, show that this number increases with an increase of the transmission rate while this number decreases when vaccination rate increases.
本研究介绍了一种确定性模型,用于模拟疫苗可预防疾病的渐进传播以及疾病发展的不同阶段。我们推导出了相关基本繁殖数的公式。为了说明所提出的模型,我们使用了 2017-2018 年也门白喉疫情的数据,并对模型参数进行了拟合。基本繁殖数对模型参数的敏感性分析表明,随着传播率的增加,基本繁殖数会增加,而当疫苗接种率增加时,基本繁殖数会减少。
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引用次数: 0
Perspectives on benchmarking foundation models for network biology 网络生物学基础模型基准的视角
Pub Date : 2024-07-11 DOI: 10.1002/qub2.68
Christina V. Theodoris
Transfer learning has revolutionized fields including natural language understanding and computer vision by leveraging large‐scale general datasets to pretrain models with foundational knowledge that can then be transferred to improve predictions in a vast range of downstream tasks. More recently, there has been a growth in the adoption of transfer learning approaches in biological fields, where models have been pretrained on massive amounts of biological data and employed to make predictions in a broad range of biological applications. However, unlike in natural language where humans are best suited to evaluate models given a clear understanding of the ground truth, biology presents the unique challenge of being in a setting where there are a plethora of unknowns while at the same time needing to abide by real‐world physical constraints. This perspective provides a discussion of some key points we should consider as a field in designing benchmarks for foundation models in network biology.
迁移学习利用大规模通用数据集对具有基础知识的模型进行预训练,然后将这些知识迁移到大量下游任务中以提高预测能力,从而给自然语言理解和计算机视觉等领域带来了革命性的变化。最近,生物领域采用迁移学习方法的情况越来越多,在大量生物数据上对模型进行预训练,并在广泛的生物应用中进行预测。然而,与自然语言不同的是,在自然语言中,人类最适合在清楚了解基本事实的情况下对模型进行评估,而生物学则面临着独特的挑战,即在存在大量未知因素的环境中,同时还需要遵守现实世界的物理限制。本视角讨论了我们在为网络生物学基础模型设计基准时应考虑的一些要点。
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引用次数: 1
In silico designing and optimization of anti‐epidermal growth factor receptor scaffolds by complementary‐determining regions‐grafting technique 通过互补决定区嫁接技术,对抗表皮生长因子受体支架进行硅设计和优化
Pub Date : 2024-07-10 DOI: 10.1002/qub2.63
Razieh Rezaei Adriani, S. M. Mousavi Gargari, Hamid Bakherad, J. Amani
Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary‐determining regions (CDRs). Small proteins with structurally preserved CDRs are promising antibodies mimetics. In this in silico study, we presented new antibody mimetics against the cancer marker epidermal growth factor receptor (EGFR) created by the CDRs grafting technique. Ten potential graft acceptor sites that efficiently immobilize the grafted CDR loops were selected from three small protein scaffolds using a computer. The three most involved CDR loops in antibody‐receptor interactions extracted from panitumumab antibody against the EGFR domain III crystal structure were then grafted to the selected scaffolds through the loop randomization technique. The combination of three CDR loops and 10 grafting sites revealed that three of the 36 combinations showed specific binding to EGFR DIII by binding energy calculations. Thus, the present strategy and selected small protein scaffolds are promising tools in the design of new binders against EGFR with high binding energy.
单克隆抗体通过其互补决定区(CDR)与靶点特异性结合,是治疗多种人类疾病的极具吸引力的药物。结构上保留了 CDR 的小蛋白是很有前景的抗体模拟物。在这项硅学研究中,我们通过 CDRs 嫁接技术,提出了针对癌症标志物表皮生长因子受体(EGFR)的新型抗体模拟物。我们利用计算机从三个小型蛋白质支架中筛选出了十个能有效固定接枝 CDR 环的潜在接枝受体位点。然后通过环路随机化技术,将从帕尼单抗抗表皮生长因子受体结构域 III 晶体结构中提取的抗体-受体相互作用中涉及最多的三个 CDR 环路嫁接到选定的支架上。通过结合能计算发现,3个CDR环和10个嫁接位点的36种组合中有3种与表皮生长因子受体DIII有特异性结合。因此,本策略和所选的小蛋白支架是设计具有高结合能的表皮生长因子受体新结合体的有效工具。
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引用次数: 0
Mathematical modeling of evolution of cell networks in epithelial tissues 上皮组织细胞网络进化的数学建模
Pub Date : 2024-07-07 DOI: 10.1002/qub2.62
I. Krasnyakov
Epithelial cell networks imply a packing geometry characterized by various cell shapes and distributions in terms of number of cell neighbors and areas. Despite such simple characteristics describing cell sheets, the formation of bubble‐like cells during the morphogenesis of epithelial tissues remains poorly understood. This study proposes a topological mathematical model of morphogenesis in a squamous epithelial. We introduce a new potential that takes into account not only the elasticity of cell perimeter and area but also the elasticity of their internal angles. Additionally, we incorporate an integral equation for chemical signaling, allowing us to consider chemo‐mechanical cell interactions. In addition to the listed factors, the model takes into account essential processes in real epithelial, such as cell proliferation and intercalation. The presented mathematical model has yielded novel insights into the packing of epithelial sheets. It has been found that there are two main states: one consists of cells of the same size, and the other consists of “bubble” cells. An example is provided of the possibility of accounting for chemo‐mechanical interactions in a multicellular environment. The introduction of a parameter determining the flexibility of cell shapes enables the modeling of more complex cell behaviors, such as considering change of cell phenotype. The developed mathematical model of morphogenesis of squamous epithelium allows progress in understanding the processes of formation of cell networks. The results obtained from mathematical modeling are of significant importance for understanding the mechanisms of morphogenesis and development of epithelial tissues. Additionally, the obtained results can be applied in developing methods to influence morphogenetic processes in medical applications.
上皮细胞网络意味着一种以各种细胞形状以及细胞邻近数量和面积分布为特征的堆积几何形状。尽管描述细胞片的特征如此简单,但人们对上皮组织形态发生过程中气泡状细胞的形成仍然知之甚少。本研究提出了鳞状上皮形态发生的拓扑数学模型。我们引入了一种新的势,它不仅考虑了细胞周长和面积的弹性,还考虑了细胞内角的弹性。此外,我们还加入了化学信号的积分方程,使我们能够考虑化学-机械细胞相互作用。除上述因素外,该模型还考虑了实际上皮细胞的基本过程,如细胞增殖和插层。所提出的数学模型使我们对上皮片的堆积有了新的认识。研究发现存在两种主要状态:一种由大小相同的细胞组成,另一种由 "气泡 "细胞组成。该研究提供了一个例子,说明在多细胞环境中考虑化学机械相互作用的可能性。通过引入一个决定细胞形状灵活性的参数,可以建立更复杂的细胞行为模型,例如考虑细胞表型的变化。所建立的鳞状上皮细胞形态发生数学模型有助于进一步了解细胞网络的形成过程。数学建模获得的结果对于理解上皮组织的形态发生和发育机制具有重要意义。此外,获得的结果还可用于开发影响形态发生过程的医学应用方法。
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引用次数: 0
Effectiveness of machine learning at modeling the relationship between Hi‐C data and copy number variation 机器学习建模 Hi-C 数据与拷贝数变异之间关系的有效性
Pub Date : 2024-07-06 DOI: 10.1002/qub2.52
Yuyang Wang, Yu Sun, Zeyu Liu, Bijia Chen, Hebing Chen, Chao Ren, Xuanwei Lin, Pengzhen Hu, Peiheng Jia, Xiang Xu, Kang Xu, Ximeng Liu, Hao Li, Xiaochen Bo
Copy number variation (CNV) refers to the number of copies of a specific sequence in a genome and is a type of chromatin structural variation. The development of the Hi‐C technique has empowered research on the spatial structure of chromatins by capturing interactions between DNA fragments. We utilized machine‐learning methods including the linear transformation model and graph convolutional network (GCN) to detect CNV events from Hi‐C data and reveal how CNV is related to three‐dimensional interactions between genomic fragments in terms of the one‐dimensional read count signal and features of the chromatin structure. The experimental results demonstrated a specific linear relation between the Hi‐C read count and CNV for each chromosome that can be well qualified by the linear transformation model. In addition, the GCN‐based model could accurately extract features of the spatial structure from Hi‐C data and infer the corresponding CNV across different chromosomes in a cancer cell line. We performed a series of experiments including dimension reduction, transfer learning, and Hi‐C data perturbation to comprehensively evaluate the utility and robustness of the GCN‐based model. This work can provide a benchmark for using machine learning to infer CNV from Hi‐C data and serves as a necessary foundation for deeper understanding of the relationship between Hi‐C data and CNV.
拷贝数变异(CNV)是指基因组中特定序列的拷贝数,是染色质结构变异的一种类型。Hi-C 技术的发展通过捕捉 DNA 片段之间的相互作用,促进了染色质空间结构的研究。我们利用线性变换模型和图卷积网络(GCN)等机器学习方法从Hi-C数据中检测CNV事件,并从一维读数信号和染色质结构特征方面揭示CNV与基因组片段间三维相互作用的关系。实验结果表明,每条染色体的 Hi-C 读数与 CNV 之间存在特定的线性关系,线性变换模型可以很好地证明这一点。此外,基于 GCN 的模型还能从 Hi-C 数据中准确提取空间结构特征,并推断出癌细胞系中不同染色体上相应的 CNV。我们进行了一系列实验,包括降维、迁移学习和 Hi-C 数据扰动,以全面评估基于 GCN 的模型的实用性和鲁棒性。这项工作为利用机器学习从 Hi-C 数据推断 CNV 提供了一个基准,也为深入理解 Hi-C 数据与 CNV 之间的关系奠定了必要的基础。
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引用次数: 0
Assessing the inhibition efficacy of clinical drugs against the main proteases of SARS‐CoV‐2 variants and other coronaviruses 评估临床药物对 SARS-CoV-2 变体和其他冠状病毒主要蛋白酶的抑制效果
Pub Date : 2024-07-06 DOI: 10.1002/qub2.60
Wenlong Zhao, C. Lupala, Shifeng Hou, Shuxin Yang, Ziqi Yan, Shujie Liao, Xuefei Li, Nan Li
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引用次数: 0
A  substructure‐aware graph neural network incorporating relation features for drug–drug interaction prediction 结合关系特征的亚结构感知图神经网络用于药物相互作用预测
Pub Date : 2024-07-06 DOI: 10.1002/qub2.66
Liangcheng Dong, Baoming Feng, Zengqian Deng, Jinlong Wang, Peihao Ni, Yuanyuan Zhang
Identifying drug–drug interactions (DDIs) is an important aspect of drug design research, and predicting DDIs serves as a crucial guarantee for avoiding potential adverse effects. Current substructure‐based prediction methods still have some limitations: (i) The process of substructure extraction does not fully exploit the graph structure information of drugs, as it only evaluates the importance of different radius substructures from a single perspective. (ii) The process of constructing drug representations has overlooked the significant impact of relation embedding on optimizing drug representations. In this work, we propose a substructure‐aware graph neural network incorporating relation features (RFSA‐DDI) for DDI prediction, which introduces a directed message passing neural network with substructure attention mechanism based on graph self‐adaptive pooling (GSP‐DMPNN) and a substructure‐aware interaction module incorporating relation features (RSAM). GSP‐DMPNN utilizes graph self‐adaptive pooling to comprehensively consider node features and local drug information for adaptive extraction of substructures. RSAM interacts drug features with relation representations to enhance their respective features individually, highlighting substructures that significantly impact predictions. RFSA‐DDI is evaluated on two real‐world datasets. Compared to existing methods, RFSA‐DDI demonstrates certain advantages in both transductive and inductive settings, effectively handling the task of predicting DDIs for unseen drugs and exhibiting good generalization capability. The experimental results show that RFSA‐DDI can effectively capture valuable structural information of drugs more accurately for DDI prediction, and provide more reliable assistance for potential DDIs detection in drug development and treatment stages.
识别药物间相互作用(DDIs)是药物设计研究的一个重要方面,而预测 DDIs 则是避免潜在不良反应的重要保证。目前基于亚结构的预测方法仍存在一些局限性:(i) 亚结构提取过程没有充分利用药物的图结构信息,因为它只是从单一角度评估不同半径亚结构的重要性。(ii) 构建药物表征的过程忽略了关系嵌入对优化药物表征的重要影响。在这项工作中,我们提出了一种结合关系特征的亚结构感知图神经网络(RFSA-DDI)用于 DDI 预测,该网络引入了基于图自适应池的具有亚结构关注机制的有向消息传递神经网络(GSP-DMPNN)和结合关系特征的亚结构感知交互模块(RSAM)。GSP-DMPNN 利用图自适应池综合考虑节点特征和本地药物信息,以自适应提取子结构。RSAM 将药物特征与关系表征相互作用,单独增强各自的特征,突出对预测有重大影响的子结构。RFSA-DDI 在两个实际数据集上进行了评估。与现有方法相比,RFSA-DDI 在转导和归纳环境中都表现出一定的优势,能有效处理预测未见药物的 DDI 任务,并表现出良好的泛化能力。实验结果表明,RFSA-DDI 能有效捕获药物的宝贵结构信息,更准确地进行 DDI 预测,为药物研发和治疗阶段的潜在 DDIs 检测提供更可靠的帮助。
{"title":"A  substructure‐aware graph neural network incorporating relation features for drug–drug interaction prediction","authors":"Liangcheng Dong, Baoming Feng, Zengqian Deng, Jinlong Wang, Peihao Ni, Yuanyuan Zhang","doi":"10.1002/qub2.66","DOIUrl":"https://doi.org/10.1002/qub2.66","url":null,"abstract":"Identifying drug–drug interactions (DDIs) is an important aspect of drug design research, and predicting DDIs serves as a crucial guarantee for avoiding potential adverse effects. Current substructure‐based prediction methods still have some limitations: (i) The process of substructure extraction does not fully exploit the graph structure information of drugs, as it only evaluates the importance of different radius substructures from a single perspective. (ii) The process of constructing drug representations has overlooked the significant impact of relation embedding on optimizing drug representations. In this work, we propose a substructure‐aware graph neural network incorporating relation features (RFSA‐DDI) for DDI prediction, which introduces a directed message passing neural network with substructure attention mechanism based on graph self‐adaptive pooling (GSP‐DMPNN) and a substructure‐aware interaction module incorporating relation features (RSAM). GSP‐DMPNN utilizes graph self‐adaptive pooling to comprehensively consider node features and local drug information for adaptive extraction of substructures. RSAM interacts drug features with relation representations to enhance their respective features individually, highlighting substructures that significantly impact predictions. RFSA‐DDI is evaluated on two real‐world datasets. Compared to existing methods, RFSA‐DDI demonstrates certain advantages in both transductive and inductive settings, effectively handling the task of predicting DDIs for unseen drugs and exhibiting good generalization capability. The experimental results show that RFSA‐DDI can effectively capture valuable structural information of drugs more accurately for DDI prediction, and provide more reliable assistance for potential DDIs detection in drug development and treatment stages.","PeriodicalId":508846,"journal":{"name":"Quantitative Biology","volume":" 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141671660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single‐cell gene regulatory network analysis for mixed cell populations 混合细胞群的单细胞基因调控网络分析
Pub Date : 2024-07-02 DOI: 10.1002/qub2.64
Junjie Tang, Changhu Wang, Fei Xiao, Ruibin Xi
Gene regulatory network (GRN) refers to the complex network formed by regulatory interactions between genes in living cells. In this paper, we consider inferring GRNs in single cells based on single‐cell RNA sequencing (scRNA‐seq) data. In scRNA‐seq, single cells are often profiled from mixed populations, and their cell identities are unknown. A common practice for single‐cell GRN analysis is to first cluster the cells and infer GRNs for every cluster separately. However, this two‐step procedure ignores uncertainty in the clustering step and thus could lead to inaccurate estimation of the networks. Here, we consider the mixture Poisson log‐normal model (MPLN) for network inference of count data from mixed populations. The precision matrices of the MPLN are the GRNs of different cell types. To avoid the intractable optimization of the MPLN’s log‐likelihood, we develop an algorithm called variational mixture Poisson log‐normal (VMPLN) to jointly estimate the GRNs of different cell types based on the variational inference method. We compare VMPLN with state‐of‐the‐art single‐cell regulatory network inference methods. Comprehensive simulation shows that VMPLN achieves better performance, especially in scenarios where different cell types have a high mixing degree. Benchmarking on real scRNA‐seq data also demonstrates that VMPLN can provide more accurate network estimation in most cases. Finally, we apply VMPLN to a large scRNA‐seq dataset from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and find that VMPLN identifies critical differences in regulatory networks in immune cells between patients with moderate and severe symptoms. The source codes are available on the GitHub website (github.com/XiDsLab/SCVMPLN).
基因调控网络(GRN)是指活细胞中基因间调控相互作用形成的复杂网络。本文考虑根据单细胞 RNA 测序(scRNA-seq)数据推断单细胞中的基因调控网络。在 scRNA-seq 中,单细胞通常是从混合群体中提取的,其细胞身份未知。单细胞 GRN 分析的常见做法是首先对细胞进行聚类,然后分别推断每个聚类的 GRN。然而,这种两步法忽略了聚类步骤中的不确定性,因此可能导致对网络的估计不准确。在此,我们考虑采用混合泊松对数正态模型(MPLN)来推断混合群体计数数据的网络。MPLN 的精确矩阵是不同细胞类型的 GRN。为了避免对 MPLN 的对数似然进行棘手的优化,我们开发了一种称为变异混合泊松对数正态(VMPLN)的算法,基于变异推理方法联合估计不同细胞类型的 GRN。我们将 VMPLN 与最先进的单细胞调控网络推断方法进行了比较。综合模拟结果表明,VMPLN 的性能更好,尤其是在不同细胞类型高度混合的情况下。真实 scRNA-seq 数据的基准测试也表明,VMPLN 在大多数情况下都能提供更准确的网络估计。最后,我们将 VMPLN 应用于严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染患者的大型 scRNA-seq 数据集,发现 VMPLN 能识别中度和重度症状患者免疫细胞调控网络的关键差异。源代码可在 GitHub 网站(github.com/XiDsLab/SCVMPLN)上获取。
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引用次数: 0
Current opinions on large cellular models 目前对大型细胞模型的看法
Pub Date : 2024-07-01 DOI: 10.1002/qub2.65
Minsheng Hao, Lei Wei, Fan Yang, Jianhua Yao, Christina V. Theodoris, Bo Wang, Xin Li, Ge Yang, Xuegong Zhang
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引用次数: 0
CShaperApp: Segmenting and analyzing cellular morphologies of the developing Caenorhabditis elegans embryo CShaperApp:分割和分析发育中的秀丽隐杆线虫胚胎的细胞形态
Pub Date : 2024-05-16 DOI: 10.1002/qub2.47
Jianfeng Cao, Lihan Hu, Guoye Guan, Zelin Li, Zhongying Zhao, Chao Tang, Hong Yan
Caenorhabditis elegans has been widely used as a model organism in developmental biology due to its invariant development. In this study, we developed a desktop software CShaperApp to segment fluorescence‐labeled images of cell membranes and analyze cellular morphologies interactively during C. elegans embryogenesis. Based on the previously proposed framework CShaper, CShaperApp empowers biologists to automatically and efficiently extract quantitative cellular morphological data with either an existing deep learning model or a fine‐tuned one adapted to their in‐house dataset. Experimental results show that it takes about 30 min to process a three‐dimensional time‐lapse (4D) dataset, which consists of 150 image stacks at a ∼1.5‐min interval and covers C. elegans embryogenesis from the 4‐cell to 350‐cell stages. The robustness of CShaperApp is also validated with the datasets from different laboratories. Furthermore, modularized implementation increases the flexibility in multi‐task applications and promotes its flexibility for future enhancements. As cell morphology over development has emerged as a focus of interest in developmental biology, CShaperApp is anticipated to pave the way for those studies by accelerating the high‐throughput generation of systems‐level quantitative data collection. The software can be freely downloaded from the website of Github (cao13jf/CShaperApp) and is executable on Windows, macOS, and Linux operating systems.
秀丽隐杆线虫(Caenorhabditis elegans)因其发育的不变性而被广泛用作发育生物学的模式生物。在这项研究中,我们开发了一款桌面软件 CShaperApp,用于在秀丽隐杆线虫胚胎发生过程中分割荧光标记的细胞膜图像并交互式分析细胞形态。CShaperApp 基于之前提出的 CShaper 框架,使生物学家能够利用现有的深度学习模型或根据其内部数据集进行微调的模型,自动、高效地提取定量的细胞形态数据。实验结果表明,处理一个三维延时(4D)数据集大约需要30分钟,该数据集由150幅图像堆叠组成,每幅图像的间隔为1.5分钟,涵盖秀丽隐杆线虫胚胎发育的4细胞至350细胞阶段。来自不同实验室的数据集也验证了 CShaperApp 的鲁棒性。此外,模块化的实现方式增加了多任务应用的灵活性,并提高了未来改进的灵活性。随着细胞形态在发育过程中的变化成为发育生物学的关注焦点,CShaperApp 预计将通过加速系统级定量数据收集的高通量生成,为这些研究铺平道路。该软件可从 Github 网站(cao13jf/CShaperApp)免费下载,并可在 Windows、macOS 和 Linux 操作系统上执行。
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引用次数: 0
期刊
Quantitative Biology
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