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Embedding-based Multimodal Learning on Pan-Squamous Cell Carcinomas for Improved Survival Outcomes 基于嵌入式多模态学习的泛鳞状细胞癌改善生存结果
Pub Date : 2024-06-11 DOI: arxiv-2406.08521
Asim Waqas, Aakash Tripathi, Paul Stewart, Mia Naeini, Ghulam Rasool
Cancer clinics capture disease data at various scales, from genetic to organlevel. Current bioinformatic methods struggle to handle the heterogeneousnature of this data, especially with missing modalities. We propose PARADIGM, aGraph Neural Network (GNN) framework that learns from multimodal, heterogeneousdatasets to improve clinical outcome prediction. PARADIGM generates embeddingsfrom multi-resolution data using foundation models, aggregates them intopatient-level representations, fuses them into a unified graph, and enhancesperformance for tasks like survival analysis. We train GNNs on pan-SquamousCell Carcinomas and validate our approach on Moffitt Cancer Center lung SCCdata. Multimodal GNN outperforms other models in patient survival prediction.Converging individual data modalities across varying scales provides a moreinsightful disease view. Our solution aims to understand the patient'scircumstances comprehensively, offering insights on heterogeneous dataintegration and the benefits of converging maximum data views.
癌症诊所从基因到器官层面捕捉各种规模的疾病数据。目前的生物信息学方法很难处理这些数据的异质性,尤其是缺失的模式。我们提出的 PARADIGM 是一种图神经网络(GNN)框架,它可以从多模态、异构数据集中学习,从而改进临床结果预测。PARADIGM 利用基础模型从多分辨率数据中生成嵌入,将它们聚合成患者级别的表示,融合成统一的图,并提高生存分析等任务的性能。我们在泛鳞状细胞癌上训练 GNN,并在 Moffitt 癌症中心的肺 SCC 数据上验证了我们的方法。多模态 GNN 在患者生存预测方面的表现优于其他模型。我们的解决方案旨在全面了解患者的情况,提供关于异构数据整合的见解以及最大数据视图融合的益处。
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引用次数: 0
How cells stay together; a mechanism for maintenance of a robust cluster explored by local and nonlocal continuum models 细胞如何保持在一起;局部和非局部连续模型探索的稳健集群维持机制
Pub Date : 2024-06-05 DOI: arxiv-2406.02846
Andreas Buttenschön, Shona Sinclair, Leah Edelstein-Keshet
Formation of organs and specialized tissues in embryonic development requiresmigration of cells to specific targets. In some instances, such cells migrateas a robust cluster. We here explore a recent local approximation of nonlocalcontinuum models by Falc'o, Baker, and Carrillo (2023). We apply theirtheoretical results by specifying biologically-based cell-cell interactions,showing how such cell communication results in an effectiveattraction-repulsion Morse potential. We then explore the clusteringinstability, the existence and size of the cluster, and its stability. We alsoextend their work by investigating the accuracy of the local approximationrelative to the full nonlocal model.
胚胎发育过程中器官和特化组织的形成需要细胞向特定目标迁移。在某些情况下,这些细胞会以强大的集群形式迁移。在此,我们探讨了 Falc'o, Baker 和 Carrillo(2023 年)最近对非局部连续模型的局部近似。我们应用了他们的理论结果,具体说明了基于生物学的细胞-细胞相互作用,展示了这种细胞交流如何导致有效的吸引-排斥莫尔斯电势。然后,我们探讨了聚类不稳定性、聚类的存在和大小及其稳定性。我们还扩展了他们的工作,研究了局部近似相对于完整非局部模型的准确性。
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引用次数: 0
Lichen-Mediated Self-Growing Construc8on Materials for Habitat Outfitting on Mars 用于火星人居装备的地衣自生长建筑材料
Pub Date : 2024-06-04 DOI: arxiv-2406.02522
Nisha Rokaya, Erin C. Carr, Richard A. Wilson, Congrui Jin
As its next step in space exploration, the National Aeronautics and SpaceAdministration (NASA) revealed plans to establish a permanent human presence onMars. To build the centrally located, monolithic habitat, NASA has a history ofexperimenting with lightweight inflatable habitats to reduce mass and volume.However, the physical structures used to outfit the inflatable must generallybe launched by a second spacecraft. This study proposes that, rather thanshipping prefabricated outfitting elements to Mars, habitat outfitting can berealized by in-situ construction using cyanobacteria and fungi as buildingagents. A synthetic lichen system, composed of diazotrophic cyanobacteria andfilamentous fungi, can be created to produce abundant biominerals (CaCO3) andbiopolymers, which will glue Martian regolith into consolidated buildingblocks. These self-growing building blocks can be assembled into variousstructures, such as floors, walls, partitions, and furniture.
作为太空探索的下一步,美国国家航空航天局(NASA)透露了在火星上建立人类永久存在的计划。为了建造位于中心位置的整体式栖息地,NASA 曾试验过轻型充气式栖息地,以减少质量和体积。然而,用于装备充气式栖息地的实体结构通常必须由第二艘航天器发射。本研究提出,与其将预制装备元件运往火星,不如利用蓝藻和真菌作为建筑材料,在原地建造栖息地装备。由重氮蓝藻和丝状真菌组成的合成地衣系统可以产生丰富的生物矿物(CaCO3)和生物聚合物,将火星岩石粘合成坚固的建筑块。这些自生长的积木可以组装成各种结构,如地板、墙壁、隔板和家具。
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引用次数: 0
The development of drug resistance in metastatic tumours under chemotherapy: an evolutionary perspective 化疗下转移性肿瘤耐药性的产生:进化的视角
Pub Date : 2024-05-30 DOI: arxiv-2405.20203
Federica Padovano, Luis Almeida, Chiara Villa
We present a mathematical model of the evolutionary dynamics of a metastatictumour under chemotherapy, comprising non-local partial differential equationsfor the phenotype-structured cell populations in the primary tumour and itsmetastasis. These equations are coupled with a physiologically-basedpharmacokinetic model of drug delivery, implementing a realistic deliveryschedule. The model is carefully calibrated from the literature, focusing onBRAF-mutated melanoma treated with Dabrafenib as a case study. By means oflong-time asymptotic analysis, global sensitivity analysis and numericalsimulations, we explore the impact of cell migration from the primary to themetastatic site, physiological aspects of the tumour sites and drug dose on thedevelopment of drug resistance and treatment efficacy. Our findings provide apossible explanation for empirical evidence indicating that chemotherapy mayfoster metastatic spread and that metastatic sites may be less impacted bychemotherapy.
我们提出了一个化疗下转移瘤进化动力学数学模型,包括原发肿瘤及其转移瘤中表型结构细胞群的非局部偏微分方程。这些方程与基于生理学的给药药动学模型相结合,实现了现实的给药时间表。该模型根据文献进行了仔细校准,以用达拉非尼治疗的BRAF突变黑色素瘤为案例进行研究。通过长时渐近分析、全局敏感性分析和数值模拟,我们探讨了细胞从原发部位向转移部位迁移、肿瘤部位的生理因素和药物剂量对耐药性和疗效发展的影响。我们的研究结果为实证证据提供了可能的解释,即化疗可能会促进转移扩散,而转移部位受到化疗的影响可能较小。
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引用次数: 0
Immune cells interactions in the tumor microenvironment 肿瘤微环境中免疫细胞的相互作用
Pub Date : 2024-05-28 DOI: arxiv-2405.18452
Mobina Tousian, Christian Solis Calero, Julio Cesar Perez Sansalvador
The tumor microenvironment (TME) plays a critical role in cancer cellproliferation, invasion, and resistance to therapy. A principal component ofthe TME is the tumor immune microenvironment (TIME), which includes variousimmune cells such as macrophages. Depending on the signals received fromenvironmental elements like IL-4 or IFN-$gamma$, macrophages can exhibitpro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. This study uses anenhanced agent-based model to simulate interactions within the TIME, focusingon the dynamic behavior of macrophages. We examine the response of cancer cellpopulations to alterations in macrophages, categorized into three differentbehaviors: M0 (initial-inactive), M1 (immune-upholding), and M2(immune-repressing), as well as environmental differentiations. The resultshighlight the significant impact of macrophage modulation on tumorproliferation and suggest potential therapeutic strategies targeting theseimmune cells.
肿瘤微环境(TME)在癌细胞增殖、侵袭和抗药性方面起着至关重要的作用。肿瘤微环境的一个主要组成部分是肿瘤免疫微环境(TIME),其中包括各种免疫细胞,如巨噬细胞。根据从IL-4或IFN-$gamma$等环境要素接收到的信号,巨噬细胞可表现出促炎症(M1)或抗炎症(M2)表型。本研究使用基于增强代理的模型模拟 TIME 内的相互作用,重点关注巨噬细胞的动态行为。我们研究了癌细胞群对巨噬细胞变化的反应,并将其分为三种不同的行为:M0(初始不活跃)、M1(免疫维持)和 M2(免疫抑制),以及环境分化。研究结果凸显了巨噬细胞调节对肿瘤扩散的重大影响,并提出了针对这些免疫细胞的潜在治疗策略。
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引用次数: 0
Active gel model for one-dimensional cell migration coupling actin flow and adhesion dynamics 连接肌动蛋白流动和粘附动力学的一维细胞迁移活性凝胶模型
Pub Date : 2024-05-27 DOI: arxiv-2405.16870
Valentin WössnerHeidelberg University, Oliver M. DrozdowskiHeidelberg University, Falko ZiebertHeidelberg University, Ulrich S. SchwarzHeidelberg University
Migration of animal cells is based on the interplay between actinpolymerization at the front, adhesion along the cell-substrate interface, andactomyosin contractility at the back. Active gel theory has been used before todemonstrate that actomyosin contractility is sufficient for polarization andself-sustained cell migration in the absence of external cues, but did notconsider the dynamics of adhesion. Likewise, migration models based on themechanosensitive dynamics of adhesion receptors usually do not include theglobal dynamics of intracellular flow. Here we show that both aspects can becombined in a minimal active gel model for one-dimensional cell migration withdynamic adhesion. This model demonstrates that load sharing between theadhesion receptors leads to symmetry breaking, with stronger adhesion at thefront, and that bistability of migration arises for intermediate adhesiveness.Local variations in adhesiveness are sufficient to switch between sessile andmotile states, in qualitative agreement with experiments.
动物细胞的迁移基于前端的肌动蛋白聚合、沿细胞-基质界面的粘附和后端的肌动蛋白收缩之间的相互作用。活性凝胶理论曾被用于证明肌动蛋白收缩力足以在没有外部线索的情况下实现极化和自我维持的细胞迁移,但并未考虑粘附的动态变化。同样,基于粘附受体机械敏感动力学的迁移模型通常不包括细胞内流动的整体动力学。在这里,我们证明了这两个方面可以结合在一个最小活性凝胶模型中,用于一维细胞迁移和动态粘附。该模型表明,粘附受体之间的负载分担会导致对称性打破,前端的粘附力更强,而迁移的双稳态性产生于中间粘附力。
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引用次数: 0
Cell migration: Beyond Brownian motion 细胞迁移:超越布朗运动
Pub Date : 2024-05-27 DOI: arxiv-2405.17578
Rainer Klages
This brief `New & Notable' (perspectives-type) article contains a mini-reviewon stochastic modelling of cell migration before elaborating on the article byKlimek et al., arXiv:2311.16753 [Biophys. J. 123, 1173-1183 (2024)].
这篇简短的 "最新与值得关注"(perspectives-type)文章包含一篇关于细胞迁移随机建模的小型综述,然后阐述了克里梅克等人的文章,arXiv:2311.16753 [Biophys. J. 123, 1173-1183 (2024)]。
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引用次数: 0
Emergent behaviour and phase transitions in spatially distributed multi-cellular metabolic networks 空间分布式多细胞代谢网络中的新兴行为和相变
Pub Date : 2024-05-22 DOI: arxiv-2405.13424
K. Narayanankutty, J. A. Pereiro-Morejon, A. Ferrero, V. Onesto, S. Forciniti, L. L. del Mercato, R. Mulet, A. De Martino, D. S. Tourigny, D. De Martino
Overflow metabolism is a ubiquitous phenomenon whereby cells in aerobicconditions excrete byproducts of glycolysis, such as lactate or acetate, intothe medium in a seemingly wasteful and polluting fashion. Whilst overflow mayconfer microbes a fitness advantage by allowing them to overcome a finiteoxidative capacity, its occurrence in higher organisms is harder to assess.Important insight was however obtained in recent experiments conducted atsingle-cell resolution, which revealed that accumulation of overflow productsin tumor cell cultures known as the Warburg effect arises from imbalances inthe dynamic and heterogeneous inter-cellular exchange network through whichcells collectively regulate the microenvironment. Here we provide aquantitative characterization of this scenario by integrating metabolic networkmodeling with diffusion constraints, statistical physics theory and single-cellexperimental flux data. On the theoretical side, we clarify howdiffusion-limited exchanges shape the space of viable metabolic states of amulti-cellular system. Specifically, a phase transition from a balanced networkof exchanges to an unbalanced overflow regime occurs as the mean cellularglucose and oxygen uptakes vary while single-cell metabolic phenotypes arehighly heterogeneous around this transition. We then show that time-resolveddata from human tumor-stroma cell co-cultures consistently map to thiscrossover region, supporting the idea that environmental deterioration reflectsa failure of coordination among recurrently interacting cells. In summary, ourfindings suggest that, rather than deriving from multiple independentcell-autonomous processes, environmental control is an emergent feature ofmulti-cellular systems.
溢出代谢是一种普遍存在的现象,在有氧条件下,细胞以一种看似浪费和污染的方式将糖酵解的副产物(如乳酸盐或醋酸盐)排泄到培养基中。然而,最近在单细胞分辨率下进行的实验获得了重要启示,该实验揭示了肿瘤细胞培养物中溢出产物的积累(即沃伯格效应)源于动态和异质细胞间交换网络的失衡,细胞通过该网络共同调节微环境。在这里,我们将新陈代谢网络模型与扩散约束、统计物理学理论和单个细胞群实验通量数据相结合,对这种情况进行了定性分析。在理论方面,我们阐明了扩散受限的交换如何塑造多细胞系统的可行代谢状态空间。具体来说,随着平均细胞葡萄糖和氧气摄入量的变化,会出现从平衡交换网络到不平衡溢流机制的相变,而在这一转变过程中,单细胞代谢表型具有高度异质性。我们随后表明,来自人类肿瘤-间质细胞共培养物的时间分辨数据始终映射到这一交叉区域,支持了环境恶化反映了反复相互作用的细胞之间协调失败的观点。总之,我们的研究结果表明,环境控制不是来自多个独立的细胞自主过程,而是多细胞系统的一个新兴特征。
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引用次数: 0
Run-and-tumble particle with saturating rates 具有饱和速率的运行和翻滚粒子
Pub Date : 2024-05-22 DOI: arxiv-2405.13521
Kavita Jain, Sakuntala Chatterjee
We consider a run-and-tumble particle whose speed and tumbling rate arespace-dependent on an infinite line. Unlike most of the previous work on suchmodels, here we make the physical assumption that at large distances, theserates saturate to a constant. For our choice of rate functions, we show that astationary state exists, and the exact steady state distribution decaysexponentially or faster and can be unimodal or bimodal. The effect ofboundedness of rates is seen in the mean-squared displacement of the particlethat displays qualitative features different from those observed in theprevious studies where it approaches the stationary state value monotonicallyin time; in contrast, here we find that if the initial position of the particleis sufficiently far from the origin, the variance in its position either variesnonmonotonically or plateaus before reaching the stationary state. Theseresults are captured quantitatively by the exact solution of the Green'sfunction when the particle has uniform speed but the tumbling rates change as astep-function in space; the insights provided by this limiting case are foundto be consistent with the numerical results for the general model.
我们考虑的是一个奔跑和翻滚的粒子,它的速度和翻滚率在无限长的直线上与空间有关。与以往关于此类模型的大多数研究不同,我们在这里提出了一个物理假设,即在大距离上,粒子的速度会饱和到一个常数。对于我们选择的速率函数,我们证明了静止态的存在,并且精确的稳态分布以指数或更快的速度衰减,可以是单峰或双峰。粒子的均方位移显示出不同于以往研究中观察到的质量特征,在以往研究中,粒子的均方位移随着时间的推移单调地接近稳态值;而在这里,我们发现如果粒子的初始位置离原点足够远,粒子位置的方差要么非单调地变化,要么在达到稳态之前趋于平稳。当粒子速度均匀但翻滚率在空间以阶跃函数变化时,格林函数的精确解定量地捕捉到了这些结果;我们发现这种极限情况提供的启示与一般模型的数值结果是一致的。
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引用次数: 0
Cellular dynamics of host-parasitoid interactions: Insights from the encapsulation process in a partially resistant host 寄主与寄生虫相互作用的细胞动力学:从部分抗性寄主的封装过程中获得的启示
Pub Date : 2024-05-13 DOI: arxiv-2405.07771
Samuel GornardEGCE, Florence Mougel, Isabelle Germon, Véronique Borday-Birraux, Pascaline Venon, Salimata Drabo, Laure Marie-Paule Kaiser-Arnauld
Cotesia typhae is an eastern African endoparasitoid braconid wasp thattargets the larval stage of the lepidopteran stem borer, Sesamia nonagrioides,a maize crop pest in Europe. The French host population is partially resistantto the Makindu strain of the wasp, allowing its development in only 40% of thecases. Resistant larvae can encapsulate the parasitoid and survive theinfection. This interaction provides a very interesting frame for investigatingthe impact of parasitism on host cellular resistance. We characterized theparasitoid ovolarval development in a permissive host and studied theencapsulation process in a resistant host by dissection and histologicalsectioning compared to that of inert chromatography beads. We measured thetotal hemocyte count in parasitized and bead-injected larvae over time tomonitor the magnitude of the immune reaction. Our results show that parasitismof resistant hosts delayed encapsulation but did not affect immune abilitiestowards inert beads. Moreover, while bead injection increased total hemocytecount, it remained constant in resistant and permissive larvae. We concludethat while Cotesia spp virulence factors are known to impair the host immunesystem, our results suggest that passive evasion could also occur.
Cotesia typhae 是一种东非内寄生性喙蜂,以鳞翅目螟虫 Sesamia nonagrioides 的幼虫期为目标,是欧洲的一种玉米作物害虫。法国的寄主种群对该蜂的马金杜(Makindu)品系具有部分抗性,仅有 40% 的病例允许其发展。抗性幼虫可以包裹寄生蜂并在感染后存活下来。这种相互作用为研究寄生虫对宿主细胞抵抗力的影响提供了一个非常有趣的框架。我们描述了寄生虫在允许寄生的宿主体内卵巢发育的特点,并通过解剖和组织学切片研究了寄生虫在抗性宿主体内的包裹过程,并与惰性层析珠的包裹过程进行了比较。我们测量了寄生幼虫和注射珠子幼虫的血细胞总数,以监测免疫反应的程度。我们的结果表明,寄生于抗性宿主的幼虫会延迟封装,但不会影响对惰性色谱珠的免疫能力。此外,虽然珠子注射会增加总血细胞数,但在抗性幼虫和允许幼虫中,总血细胞数保持不变。我们的结论是,虽然已知 Cotesia spp 的致病因子会损害宿主的免疫系统,但我们的结果表明被动规避也可能发生。
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引用次数: 0
期刊
arXiv - QuanBio - Cell Behavior
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