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Probing leukemia cells behavior under starvation 探究白血病细胞在饥饿状态下的行为
Pub Date : 2024-08-17 DOI: arxiv-2408.09219
Simone Scalise, Giorgio Gosti, Giancarlo Ruocco, Giovanna Peruzzi, Mattia Miotto
The ability of a cancer cell population to achieve heterogeneity in theirphenotype distributions offers advantages in tumor invasiveness and drugresistance. Studying the mechanisms behind such observed heterogeneity inmammalian cells presents challenges due for instance to the prolongedproliferation times compared to widely studied unicellular organisms likebacteria and yeast. Here, we studied the response of leukemia cell populationsto serum starvation via a protocol, we recently developed, that makes use oflive cell fluorescence and flow cytometry in combination with a quantitativeanalytical model to follow the population proliferation while monitoring thedynamics of its phenotype distributions. We found that upon switching between aserum-rich to a serum-poor media, leukemia cells (i) maintain a memory of theprevious environment up to one generation even in the presence of severemedium-depletion, before (ii) adapting their growth and division rates to thenovel environment while preserving a sizer-like division strategy. Finally,looking at the mitochondria content of the proliferating vs non-proliferatingcells, we found that the latter is characterized by a higher number of oldermitochondria, suggesting a possible functional role of the observed asymmetricpartitioning of (aged) mitochondria in leukemia cells.
癌细胞群体的表型分布具有异质性,这为肿瘤的侵袭性和抗药性提供了优势。与细菌和酵母等广泛研究的单细胞生物相比,哺乳动物细胞的增殖时间较长,因此研究哺乳动物细胞中观察到的这种异质性背后的机制是一项挑战。在这里,我们研究了白血病细胞群对血清饥饿的反应,我们最近开发了一种方案,利用活细胞荧光和流式细胞仪,结合定量分析模型来跟踪细胞群的增殖,同时监测其表型分布的动态变化。我们发现,从富含血清的培养基转换到贫血清的培养基时,白血病细胞(i)即使在介质严重缺乏的情况下,也会对上一代的环境保持记忆长达一代,然后(ii)在保持类似分裂策略的同时,使其生长和分裂率适应新的环境。最后,在观察增殖细胞与非增殖细胞的线粒体含量时,我们发现后者的特点是有更多的老线粒体,这表明在白血病细胞中观察到的(老化)线粒体不对称分布可能具有功能性作用。
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引用次数: 0
mRNA2vec: mRNA Embedding with Language Model in the 5'UTR-CDS for mRNA Design mRNA2vec:在 5'UTR-CDS 中嵌入语言模型,进行 mRNA 设计
Pub Date : 2024-08-16 DOI: arxiv-2408.09048
Honggen Zhang, Xiangrui Gao, June Zhang, Lipeng Lai
Messenger RNA (mRNA)-based vaccines are accelerating the discovery of newdrugs and revolutionizing the pharmaceutical industry. However, selectingparticular mRNA sequences for vaccines and therapeutics from extensive mRNAlibraries is costly. Effective mRNA therapeutics require carefully designedsequences with optimized expression levels and stability. This paper proposes anovel contextual language model (LM)-based embedding method: mRNA2vec. Incontrast to existing mRNA embedding approaches, our method is based on theself-supervised teacher-student learning framework of data2vec. We jointly usethe 5' untranslated region (UTR) and coding sequence (CDS) region as the inputsequences. We adapt our LM-based approach specifically to mRNA by 1)considering the importance of location on the mRNA sequence with probabilisticmasking, 2) using Minimum Free Energy (MFE) prediction and Secondary Structure(SS) classification as additional pretext tasks. mRNA2vec demonstratessignificant improvements in translation efficiency (TE) and expression level(EL) prediction tasks in UTR compared to SOTA methods such as UTR-LM. It alsogives a competitive performance in mRNA stability and protein production leveltasks in CDS such as CodonBERT.
以信使核糖核酸(mRNA)为基础的疫苗正在加速新药的发现,并给制药业带来革命性的变化。然而,从庞大的 mRNA 库中挑选用于疫苗和治疗的特定 mRNA 序列成本高昂。有效的 mRNA 疗法需要精心设计的具有优化表达水平和稳定性的序列。本文提出了一种基于上下文语言模型(LM)的嵌入方法:mRNA2vec。与现有的 mRNA 嵌入方法不同,我们的方法基于 data2vec 的自我监督师生学习框架。我们共同使用 5' 非翻译区(UTR)和编码序列(CDS)区域作为输入序列。与 UTR-LM 等 SOTA 方法相比,mRNA2vec 在 UTR 的翻译效率(TE)和表达水平(EL)预测任务上有显著提高。此外,它在 CDS(如 CodonBERT)中的 mRNA 稳定性和蛋白质生产水平任务方面的表现也很有竞争力。
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引用次数: 0
Long-term tracking of social structure in groups of rats 长期追踪大鼠群体的社会结构
Pub Date : 2024-08-16 DOI: arxiv-2408.08945
Mate NagyMTA-ELTE Statistical and Biological Physics Research Group, Budapest, HungaryMTA-ELTE Lendulet Collective Behaviour Research Group, Budapest, HungaryDepartment of Biological Physics, Eotvos Lorand University, Budapest, HungaryDepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ, USAPrinceton Neuroscience Institute, Princeton University, Princeton, NJ, USALewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA, Jacob D. DavidsonDepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ, USAPrinceton Neuroscience Institute, Princeton University, Princeton, NJ, USALewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA, Gabor VasarhelyiMTA-ELTE Statistical and Biological Physics Research Group, Budapest, HungaryDepartment of Biological Physics, Eotvos Lorand University, Budapest, Hungary, Daniel AbelMTA-ELTE Statistical and Biological Physics Research Group, Budapest, Hungary, Eniko KubinyiDepartment of Ethology, Eotvos Lorand University, Budapest, HungaryMTA-ELTE Comparative Ethology Research Group, Budapest, HungaryResearch Centre for Natural Sciences, Budapest, Hungary, Ahmed El HadyDepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ, USAPrinceton Neuroscience Institute, Princeton University, Princeton, NJ, USALewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA, Tamas VicsekMTA-ELTE Statistical and Biological Physics Research Group, Budapest, HungaryDepartment of Biological Physics, Eotvos Lorand University, Budapest, Hungary
Rodents serve as an important model for examining both individual andcollective behavior. Dominance within rodent social structures can determineaccess to critical resources, such as food and mating opportunities. Yet, manyaspects of the intricate interplay between individual behaviors and theresulting group social hierarchy, especially its evolution over time, remainunexplored. In this study, we utilized an automated tracking system thatcontinuously monitored groups of male rats for over 250 days to enable anin-depth analysis of individual behavior and the overarching group dynamic. Wedescribe the evolution of social structures within a group and additionallyinvestigate how past behaviors influence the emergence of new socialhierarchies when group composition and experimental area changes. Notably, wefind that conventional individual and pairwise tests exhibit a weak correlationwith group behavior, highlighting their limited accuracy in predictingbehavioral outcomes in a collective context. These results emphasize thecontext-dependence of social behavior as an emergent property of interactionswithin a group and highlight the need to measure and quantify social behaviorin more naturalistic environments.
啮齿动物是研究个体行为和集体行为的重要模型。啮齿动物社会结构中的支配地位可以决定能否获得关键资源,如食物和交配机会。然而,个体行为与由此产生的群体社会等级制度之间错综复杂的相互作用,特别是其随时间的演变,在许多方面仍有待探索。在这项研究中,我们利用自动跟踪系统对雄鼠群体进行了超过250天的持续监测,从而对个体行为和群体的总体动态进行了深入分析。我们描述了群体内社会结构的演化,并进一步研究了当群体组成和实验区域发生变化时,过去的行为如何影响新社会等级的出现。值得注意的是,我们发现传统的个体测试和配对测试与群体行为的相关性很弱,这凸显了它们在预测集体背景下行为结果的准确性有限。这些结果强调了社会行为作为群体内部互动的一种新兴属性对环境的依赖性,并突出了在更自然的环境中测量和量化社会行为的必要性。
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引用次数: 0
Escape cascades as a behavioral contagion process with adaptive network dynamics 逃逸级联是一种具有自适应网络动力学的行为传染过程
Pub Date : 2024-08-09 DOI: arxiv-2408.05096
Wenhan Wu, Xiaoping Zheng, Pawel Romanczuk
Complex behavioral contagion in collective evasion of mobile animal groupscan be predicted by reconstructing quantitative interaction networks. Based onthe assumption of time-scale separation between a fast contagion process and aslower movement response, the underlying interaction networks have beenpreviously assumed to be static, determined by the spatial structure at theonset of the collective escape response. This idealization does not account forthe temporal evolution of the spatial network structure, which may have a majorimpact on the behavioral contagion dynamics. Here, we propose aspatially-explicit, agent-based model for the coupling between behavioralcontagion and the network dynamics originating from the spreading movementresponse. We explore the impact of movement parameters (startle speed, initialdirectionality, and directional noise) on average cascade size. By conductingnumerical simulations for different density levels, we show that increasingescape speed suppresses the cascade size in most cases, that the cascade sizedepends strongly on the movement direction of the initially startledindividual, and that large variability in the direction of individual escapemovements (rotational noise) will typically promote the spread of behavioralcontagion through spatial groups. Our work highlights the importance ofaccounting for movement dynamics in behavioral contagion, and facilitates ourunderstanding of rapid coordinated response and collective informationprocessing in animal groups.
通过重建定量相互作用网络,可以预测移动动物群体集体逃避时的复杂行为传染。基于快速传染过程与较慢移动反应之间时间尺度分离的假设,以前一直认为基本的相互作用网络是静态的,由集体逃避反应开始时的空间结构决定。这种理想化并没有考虑到空间网络结构的时间演化,而这种演化可能会对行为传染动力学产生重大影响。在这里,我们提出了一个基于空间的显式代理模型,用于研究行为传染与源自扩散运动反应的网络动力学之间的耦合。我们探讨了运动参数(惊吓速度、初始方向性和方向噪声)对平均级联规模的影响。通过对不同密度水平进行数值模拟,我们发现在大多数情况下,增加逃逸速度会抑制级联大小,级联大小与最初受惊个体的运动方向密切相关,个体逃逸方向的巨大变异(旋转噪声)通常会促进行为传染在空间群中的传播。我们的研究强调了在行为传染中考虑运动动态的重要性,并有助于我们理解动物群体的快速协调反应和集体信息处理。
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引用次数: 0
Robust Approximate Characterization of Single-Cell Heterogeneity in Microbial Growth 微生物生长中单细胞异质性的稳健近似表征
Pub Date : 2024-08-08 DOI: arxiv-2408.04501
Richard D. Paul, Johannes Seiffarth, Hanno Scharr, Katharina Nöh
Live-cell microscopy allows to go beyond measuring average features ofcellular populations to observe, quantify and explain biological heterogeneity.Deep Learning-based instance segmentation and cell tracking form the goldstandard analysis tools to process the microscopy data collected, but trackingin particular suffers severely from low temporal resolution. In this work, weshow that approximating cell cycle time distributions in microbial colonies ofC. glutamicum is possible without performing tracking, even at low temporalresolution. To this end, we infer the parameters of a stochastic multi-stagebirth process model using the Bayesian Synthetic Likelihood method at varyingtemporal resolutions by subsampling microscopy sequences, for which groundtruth tracking is available. Our results indicate, that the proposed approachyields high quality approximations even at very low temporal resolution, wheretracking fails to yield reasonable results.
基于深度学习的实例分割和细胞追踪是处理收集到的显微镜数据的黄金标准分析工具,但追踪尤其受到低时间分辨率的严重影响。在这项工作中,我们展示了即使在低时间分辨率下,也可以在不进行跟踪的情况下近似计算谷氨酸杆菌微生物菌落中的细胞周期时间分布。为此,我们使用贝叶斯合成似然法,在不同的时间分辨率下,通过对显微镜序列进行子采样,推断出一个随机多阶段繁殖过程模型的参数。我们的研究结果表明,即使在时间分辨率非常低的情况下,所提出的方法也能得到高质量的近似值,而在这种情况下,跟踪无法得到合理的结果。
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引用次数: 0
Question Rephrasing for Quantifying Uncertainty in Large Language Models: Applications in Molecular Chemistry Tasks 在大型语言模型中量化不确定性的问题重述:分子化学任务中的应用
Pub Date : 2024-08-07 DOI: arxiv-2408.03732
Zizhang Chen, Pengyu Hong, Sandeep Madireddy
Uncertainty quantification enables users to assess the reliability ofresponses generated by large language models (LLMs). We present a novelQuestion Rephrasing technique to evaluate the input uncertainty of LLMs, whichrefers to the uncertainty arising from equivalent variations of the inputsprovided to LLMs. This technique is integrated with sampling methods thatmeasure the output uncertainty of LLMs, thereby offering a more comprehensiveuncertainty assessment. We validated our approach on property prediction andreaction prediction for molecular chemistry tasks.
不确定性量化使用户能够评估大型语言模型(LLM)生成的回答的可靠性。我们提出了一种新颖的问题重述技术来评估 LLM 的输入不确定性,即 LLM 输入等效变化所产生的不确定性。该技术与测量 LLM 输出不确定性的采样方法相结合,从而提供了更全面的不确定性评估。我们在分子化学任务的性质预测和反应预测中验证了我们的方法。
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引用次数: 0
Beta regression mixed model applied to sensory analysis 应用于感官分析的贝塔回归混合模型
Pub Date : 2024-08-06 DOI: arxiv-2408.03240
João César Reis Alves, Gabriel Rodrigues Palma, Idemauro Antonio Rodrigues de Lara
Sensory analysis is an important area that the food industry can use toinnovate and improve its products. This study involves a sample of individualswho can be trained or not to assess a product using a hedonic scale or notes,where the experimental design is a balanced incomplete block design. In thiscontext, integrating sensory analysis with effective statistical methods, whichconsider the nature of the response variables, is essential to answer the aimof the experimental study. Some techniques are available to analyse sensorydata, such as response surface models or categorical models. This articleproposes using beta regression as an alternative to the proportional oddsmodel, addressing some convergence problems, especially regarding the number ofparameters. Moreover, the beta distribution is flexible for heteroscedasticityand asymmetry data. To this end, we conducted simulation studies that showedagreement rates in product selection using both models. Also, we presented amotivational study that was developed to select prebiotic drinks based oncashew nuts added to grape juice. In this application, the beta regressionmixed model results corroborated with the selected formulations using theproportional mixed model.
感官分析是食品行业用于创新和改进产品的一个重要领域。本研究涉及的样本是经过培训或未经过培训的个人,他们可以使用享乐量表或笔记对产品进行评估,实验设计为平衡不完全区组设计。在这种情况下,将感官分析与考虑响应变量性质的有效统计方法相结合,对于实现实验研究的目标至关重要。目前已有一些分析感官数据的技术,如响应面模型或分类模型。本文建议使用贝塔回归作为比例概率模型的替代方法,以解决一些收敛问题,尤其是参数数量方面的问题。此外,贝塔分布对于异方差和不对称数据具有灵活性。为此,我们进行了模拟研究,显示了使用这两种模型进行产品选择时的一致率。此外,我们还介绍了一项动机研究,该研究旨在选择基于腰果添加到葡萄汁中的益生菌饮料。在这一应用中,贝塔回归混合模型的结果与使用比例混合模型选出的配方相吻合。
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引用次数: 0
Fast Whole-Brain MR Multi-Parametric Mapping with Scan-Specific Self-Supervised Networks 利用特定扫描自监督网络快速绘制全脑 MR 多参数图谱
Pub Date : 2024-08-06 DOI: arxiv-2408.02988
Amir Heydari, Abbas Ahmadi, Tae Hyung Kim, Berkin Bilgic
Quantification of tissue parameters using MRI is emerging as a powerful toolin clinical diagnosis and research studies. The need for multiple long scanswith different acquisition parameters prohibits quantitative MRI from reachingwidespread adoption in routine clinical and research exams. Acceleratedparameter mapping techniques leverage parallel imaging, signal modelling anddeep learning to offer more practical quantitative MRI acquisitions. However,the achievable acceleration and the quality of maps are often limited. JointMAPLE is a recent state-of-the-art multi-parametric and scan-specific parametermapping technique with promising performance at high acceleration rates. Itsynergistically combines parallel imaging, model-based and machine learningapproaches for joint mapping of T1, T2*, proton density and the fieldinhomogeneity. However, Joint MAPLE suffers from prohibitively longreconstruction time to estimate the maps from a multi-echo, multi-flip angle(MEMFA) dataset at high resolution in a scan-specific manner. In this work, wepropose a faster version of Joint MAPLE which retains the mapping performanceof the original version. Coil compression, random slice selection,parameter-specific learning rates and transfer learning are synergisticallycombined in the proposed framework. It speeds-up the reconstruction time up to700 times than the original version and processes a whole-brain MEMFA datasetin 21 minutes on average, which originally requires ~260 hours for Joint MAPLE.The mapping performance of the proposed framework is ~2-fold better than thestandard and the state-of-the-art evaluated reconstruction techniques onaverage in terms of the root mean squared error.
利用核磁共振成像对组织参数进行定量分析正在成为临床诊断和研究的有力工具。由于需要使用不同的采集参数进行多次长时间扫描,定量 MRI 无法在常规临床和研究检查中得到广泛应用。加速参数映射技术利用并行成像、信号建模和深度学习来提供更实用的定量 MRI 采集。然而,可实现的加速度和制图质量往往受到限制。JointMAPLE是一种最新的多参数和特定扫描参数成像技术,在高加速度下具有良好的性能。它协同结合了并行成像、基于模型和机器学习的方法,用于联合绘制 T1、T2*、质子密度和同质性场图。然而,Joint MAPLE 在以特定扫描方式从高分辨率多回波、多翻转角度(MEMFA)数据集估算图谱时,存在重建时间过长的问题。在这项工作中,我们提出了一种更快的联合 MAPLE 版本,它保留了原始版本的映射性能。在提出的框架中,线圈压缩、随机切片选择、特定参数学习率和迁移学习被协同结合在一起。它将重建时间加快到原始版本的 700 倍,处理全脑 MEMFA 数据集的平均时间为 21 分钟,而联合 MAPLE 原本需要约 260 个小时。
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引用次数: 0
Tensorial template matching for fast cross-correlation with rotations and its application for tomography 用于旋转快速交叉相关的张量模板匹配及其在断层扫描中的应用
Pub Date : 2024-08-05 DOI: arxiv-2408.02398
Antonio Martinez-SanchezUniversity of Murcia, Spain, Ulrike HombergThermo Fisher Scientific, José María AlmiraUniversity of Murcia, Spain, Harold PhelippeauThermo Fisher Scientific
Object detection is a main task in computer vision. Template matching is thereference method for detecting objects with arbitrary templates. However,template matching computational complexity depends on the rotation accuracy,being a limiting factor for large 3D images (tomograms). Here, we implement anew algorithm called tensorial template matching, based on a mathematicalframework that represents all rotations of a template with a tensor field.Contrary to standard template matching, the computational complexity of thepresented algorithm is independent of the rotation accuracy. Using both,synthetic and real data from tomography, we demonstrate that tensorial templatematching is much faster than template matching and has the potential to improveits accuracy
物体检测是计算机视觉领域的一项主要任务。模板匹配是利用任意模板检测物体的一种参考方法。然而,模板匹配的计算复杂度取决于旋转精度,这对于大型三维图像(断层图像)来说是一个限制因素。与标准模板匹配相反,本算法的计算复杂度与旋转精度无关。与标准模板匹配算法相反,本算法的计算复杂度与旋转精度无关。我们利用断层扫描的合成数据和真实数据证明,张量模板匹配比模板匹配快得多,而且有可能提高其精度
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引用次数: 0
A four-step Bayesian workflow for improving ecological science 改进生态科学的四步贝叶斯工作流程
Pub Date : 2024-08-05 DOI: arxiv-2408.02603
EM Wolkovich, T Jonathan Davies, William D Pearse, Michael Betancourt
Growing anthropogenic pressures have increased the need for robust predictivemodels. Meeting this demand requires approaches that can handle bigger data toyield forecasts that capture the variability and underlying uncertainty ofecological systems. Bayesian models are especially adept at this and aregrowing in use in ecology. Yet many ecologists today are not trained to takeadvantage of the bigger ecological data needed to generate more flexible robustmodels. Here we describe a broadly generalizable workflow for statisticalanalyses and show how it can enhance training in ecology. Building on theincreasingly computational toolkit of many ecologists, this approach leveragessimulation to integrate model building and testing for empirical data morefully with ecological theory. In turn this workflow can fit models that aremore robust and well-suited to provide new ecological insights -- allowing usto refine where to put resources for better estimates, better models, andbetter forecasts.
日益增长的人为压力增加了对稳健预测模型的需求。要满足这一需求,就必须采用能够处理更多数据、能够捕捉到生态系统的变异性和潜在不确定性的预测方法。贝叶斯模型尤其擅长于此,在生态学中的应用也越来越广泛。然而,当今许多生态学家并没有接受过培训,无法利用更大的生态数据来生成更灵活、更稳健的模型。在这里,我们描述了一种可广泛推广的统计分析工作流程,并展示了它如何能加强生态学方面的培训。这种方法以许多生态学家日益增长的计算工具包为基础,利用模拟将模型构建和经验数据测试与生态理论更有效地结合起来。反过来,这种工作流程也能拟合出更稳健、更适合提供新生态见解的模型--让我们可以调整资源投放的方向,以获得更好的估计、更好的模型和更好的预测。
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引用次数: 0
期刊
arXiv - QuanBio - Quantitative Methods
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