arXiv - QuanBio - Subcellular Processes最新文献_第5页

T cell receptor binding prediction: A machine learning revolution T 细胞受体结合预测：机器学习革命

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-12-27 DOI: arxiv-2312.16594

Anna Weber, Aurélien Pélissier, María Rodríguez Martínez

{"title":"T cell receptor binding prediction: A machine learning revolution","authors":"Anna Weber, Aurélien Pélissier, María Rodríguez Martínez","doi":"arxiv-2312.16594","DOIUrl":"https://doi.org/arxiv-2312.16594","url":null,"abstract":"Recent advancements in immune sequencing and experimental techniques are\u0000generating extensive T cell receptor (TCR) repertoire data, enabling the\u0000development of models to predict TCR binding specificity. Despite the\u0000computational challenges due to the vast diversity of TCRs and epitopes,\u0000significant progress has been made. This paper discusses the evolution of the\u0000computational models developed for this task, with a focus on machine learning\u0000efforts, including the early unsupervised clustering approaches, supervised\u0000models, and the more recent applications of Protein Language Models (PLMs). We\u0000critically assess the most prominent models in each category, and discuss\u0000recurrent challenges, such as the lack of generalization to new epitopes,\u0000dataset biases, and biases in the validation design of the models. Furthermore, our paper discusses the transformative role of transformer-based\u0000protein models in bioinformatics. These models, pretrained on extensive\u0000collections of unlabeled protein sequences, can convert amino acid sequences\u0000into vectorized embeddings that capture important biological properties. We\u0000discuss recent attempts to leverage PLMs to deliver very competitive\u0000performances in TCR-related tasks. Finally, we address the pressing need for\u0000improved interpretability in these often opaque models, proposing strategies to\u0000amplify their impact in the field.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064251","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

mRNA translation from a unidirectional traffic perspective 从单向运输角度看 mRNA 翻译

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-12-19 DOI: arxiv-2312.12062

Binil Shyam T V, Rati Sharma

{"title":"mRNA translation from a unidirectional traffic perspective","authors":"Binil Shyam T V, Rati Sharma","doi":"arxiv-2312.12062","DOIUrl":"https://doi.org/arxiv-2312.12062","url":null,"abstract":"mRNA translation is a crucial process that leads to protein synthesis in\u0000living cells. Therefore, it is a process that needs to work optimally for a\u0000cell to stay healthy and alive. With advancements in microscopy and novel\u0000experimental techniques, a lot of the intricate details about the translation\u0000mechanism are now known. However, the why and how of this mechanism are still\u0000ill understood, and therefore, is an active area of research. Theoretical\u0000studies of mRNA translation typically view it in terms of the Totally\u0000Asymmetric Simple Exclusion Process or TASEP. Various works have used the TASEP\u0000model in order to study a wide range of phenomena and factors affecting\u0000translation, such as ribosome traffic on an mRNA under noisy (codon-dependent\u0000or otherwise) conditions, ribosome stalling, premature termination, ribosome\u0000reinitiation and dropoff, codon-dependent elongation and competition among mRNA\u0000for ribosomes, among others. In this review, we relay the history and physics\u0000of the translation process in terms of the TASEP framework. In particular, we\u0000discuss the viability and evolution of this model and its limitations while\u0000also formulating the reasons behind its success. Finally, we also identify gaps\u0000in the existing literature and suggest possible extensions and applications\u0000that will lead to a better understanding of ribosome traffic on the mRNA.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138821030","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

Target search on DNA -- effect of coiling 在 DNA 上搜索目标 - 卷绕的影响

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-12-10 DOI: arxiv-2312.05876

Michael A. Lomholt, Ralf Metzler

引用次数: 0

Gene expression in growing cells: A biophysical primer 生长细胞中的基因表达:生物物理引物

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-11-20 DOI: arxiv-2311.12143

Ido Golding, Ariel Amir

{"title":"Gene expression in growing cells: A biophysical primer","authors":"Ido Golding, Ariel Amir","doi":"arxiv-2311.12143","DOIUrl":"https://doi.org/arxiv-2311.12143","url":null,"abstract":"Cell growth and gene expression, essential elements of all living systems,\u0000have long been the focus of biophysical interrogation. Advances in single-cell\u0000methods have invigorated theoretical studies into these processes. However,\u0000until recently, there was little dialog between the two areas of study. Most\u0000theoretical models for gene regulation assumed gene activity to be oblivious to\u0000the progression of the cell cycle between birth and division. But there are\u0000numerous ways in which the periodic character of all cellular observables can\u0000modulate gene expression. The molecular factors required for transcription and\u0000translation increase in number during the cell cycle, but are also diluted due\u0000to the continuous increase in cell volume. The replication of the genome\u0000changes the dosage of those same cellular players but also provides competing\u0000targets for regulatory binding. Finally, cell division reduces their number\u0000again, and so forth. Stochasticity is inherent to all these biological\u0000processes, manifested in fluctuations in the synthesis and degradation of new\u0000cellular components as well as the random partitioning of molecules at each\u0000cell division. The notion of gene expression as stationary is thus hard to\u0000justify. In this review, we survey the emerging paradigm of cell-cycle\u0000regulated gene expression, with an emphasis on the global expression patterns\u0000rather than gene-specific regulation. We discuss recent experimental reports\u0000where cell growth and gene expression were simultaneously measured in\u0000individual cells, providing first glimpses into the coupling between the two.\u0000While the experimental findings, not surprisingly, differ among genes and\u0000organisms, several theoretical models have emerged that attempt to reconcile\u0000these differences and form a unifying framework for understanding gene\u0000expression in growing cells.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510933","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

Modeling ionic flow between small targets: insights from diffusion and electro-diffusion theory 模拟小目标之间的离子流动:从扩散和电扩散理论的见解

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-11-14 DOI: arxiv-2311.08169

Frédéric Paquin-Lefebvre, David Holcman

{"title":"Modeling ionic flow between small targets: insights from diffusion and electro-diffusion theory","authors":"Frédéric Paquin-Lefebvre, David Holcman","doi":"arxiv-2311.08169","DOIUrl":"https://doi.org/arxiv-2311.08169","url":null,"abstract":"The flow of ions through permeable channels causes voltage drop in\u0000physiological nanodomains such as synapses, dendrites and dendritic spines, and\u0000other protrusions. How the voltage changes around channels in these nanodomains\u0000has remained poorly studied. We focus this book chapter on summarizing recent\u0000efforts in computing the steady-state current, voltage and ionic concentration\u0000distributions based on the Poisson-Nernst-Planck equations as a model of\u0000electro-diffusion. We first consider the spatial distribution of an uncharged\u0000particle density and derive asymptotic formulas for the concentration\u0000difference by solving the Laplace's equation with mixed boundary conditions. We\u0000study a constant particles injection rate modeled by a Neumann flux condition\u0000at a channel represented by a small boundary target, while the injected\u0000particles can exit at one or several narrow patches. We then discuss the case\u0000of two species (positive and negative charges) and take into account motions\u0000due to both concentration and electrochemical gradients. The voltage resulting\u0000from charge interactions is calculated by solving the Poisson's equation. We\u0000show how deep an influx diffusion propagates inside a nanodomain, for\u0000populations of both uncharged and charged particles. We estimate the\u0000concentration and voltage changes in relations with geometrical parameters and\u0000quantify the impact of membrane curvature.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510941","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

Phosphatidylserine transport in cell life and death 磷脂酰丝氨酸在细胞生与死中的转运

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-11-09 DOI: arxiv-2311.05223

Alenka {Č}opi{č}CRBM, Thibaud DieudonnéI2BC, Guillaume LenoirI2BC

引用次数: 0

Inferring stochastic rates from heterogeneous snapshots of particle positions 从粒子位置的非均匀快照推断随机速率

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-11-08 DOI: arxiv-2311.04880

Christopher E. Miles, Scott A. McKinley, Fangyuan Ding, Richard B. Lehoucq

{"title":"Inferring stochastic rates from heterogeneous snapshots of particle positions","authors":"Christopher E. Miles, Scott A. McKinley, Fangyuan Ding, Richard B. Lehoucq","doi":"arxiv-2311.04880","DOIUrl":"https://doi.org/arxiv-2311.04880","url":null,"abstract":"Many imaging techniques for biological systems -- like fixation of cells\u0000coupled with fluorescence microscopy -- provide sharp spatial resolution in\u0000reporting locations of individuals at a single moment in time but also destroy\u0000the dynamics they intend to capture. These snapshot observations contain no\u0000information about individual trajectories, but still encode information about\u0000movement and demographic dynamics, especially when combined with a\u0000well-motivated biophysical model. The relationship between spatially evolving\u0000populations and single-moment representations of their collective locations is\u0000well-established with partial differential equations (PDEs) and their inverse\u0000problems. However, experimental data is commonly a set of locations whose\u0000number is insufficient to approximate a continuous-in-space PDE solution. Here,\u0000motivated by popular subcellular imaging data of gene expression, we embrace\u0000the stochastic nature of the data and investigate the mathematical foundations\u0000of parametrically inferring demographic rates from snapshots of particles\u0000undergoing birth, diffusion, and death in a nuclear or cellular domain. Toward\u0000inference, we rigorously derive a connection between individual particle paths\u0000and their presentation as a Poisson spatial process. Using this framework, we\u0000investigate the properties of the resulting inverse problem and study factors\u0000that affect quality of inference. One pervasive feature of this experimental\u0000regime is the presence of cell-to-cell heterogeneity. Rather than being a\u0000hindrance, we show that cell-to-cell geometric heterogeneity can increase the\u0000quality of inference on dynamics for certain parameter regimes. Altogether, the\u0000results serve as a basis for more detailed investigations of subcellular\u0000spatial patterns of RNA molecules and other stochastically evolving populations\u0000that can only be observed for single instants in their time evolution.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511127","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

A Colour-Encoded Nanometric Ruler for Axial Super-Resolution Microscopies 用于轴向超分辨率显微镜的颜色编码纳米尺

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-11-01 DOI: arxiv-2311.00590

Ilya Olevsko, Omer Shavit, Moshe Feldberg, Yossi Abulafia, Adi Salomon, Martin Oheim

{"title":"A Colour-Encoded Nanometric Ruler for Axial Super-Resolution Microscopies","authors":"Ilya Olevsko, Omer Shavit, Moshe Feldberg, Yossi Abulafia, Adi Salomon, Martin Oheim","doi":"arxiv-2311.00590","DOIUrl":"https://doi.org/arxiv-2311.00590","url":null,"abstract":"Recent progress has boosted the resolving power of optical microscopies to\u0000spatial dimensions well below the diffraction limit. Yet, axial\u0000super-resolution and axial single-molecule localisation typically require more\u0000complicated implementations than their lateral counterparts. In the present\u0000work, we propose a simple solution for axial metrology by providing a\u0000multi-layered single-excitation, dual-emission test slide, in which axial\u0000distance is colour-encoded. Our test slide combines on a standard microscope\u0000coverslip substrate two flat, thin, uniform and brightly emitting fluorophore\u0000layers, separated by a nanometric transparent spacer layer having a refractive\u0000index close to a biological cell. The ensemble is sealed in an index-matched\u0000protective polymer. As a proof-of-principle, we estimate the light confinement\u0000resulting from evanescent-wave excitation in total internal reflection\u0000fluorescence (TIRF) microscopy. Our test sample permits, even for the\u0000non-expert user, a facile axial metrology at the sub-100-nm scale, a critical\u0000requirement for axial super-resolution, as well as near-surface imaging,\u0000spectroscopy and sensing.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510937","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

Form, function, mind: what doesn't compute (and what might) 形式、功能、思维:哪些不能计算(哪些可以计算)

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-10-21 DOI: arxiv-2310.13910

Stuart A. Newman

引用次数: 0

Minimal Mechanisms of Microtubule Length Regulation in Living Cells 活细胞中微管长度调节的最小机制

arXiv - QuanBio - Subcellular Processes Pub Date : 2023-10-20 DOI: arxiv-2310.13666

Anna C Nelson, Melissa Rolls, Maria-Veronica Ciocanel, Scott A McKinley

{"title":"Minimal Mechanisms of Microtubule Length Regulation in Living Cells","authors":"Anna C Nelson, Melissa Rolls, Maria-Veronica Ciocanel, Scott A McKinley","doi":"arxiv-2310.13666","DOIUrl":"https://doi.org/arxiv-2310.13666","url":null,"abstract":"The microtubule cytoskeleton is responsible for sustained, long-range\u0000intracellular transport of mRNAs and proteins in neurons. Neuronal microtubules\u0000must be stable enough to ensure reliable transport, but they also undergo\u0000dynamic instability, as their plus and minus ends continuously switch between\u0000growth and shrinking. This process allows for continuous rebuilding of the\u0000cytoskeleton and for flexibility in injury settings. Motivated by textit{in\u0000vivo} experimental data on microtubule behavior in textit{Drosophila} neurons,\u0000we propose a spatially-explicit mathematical model of dendritic microtubule\u0000dynamics. We find that experimental parameters predict unbounded microtubule\u0000growth. We therefore investigate two minimal length-limiting factors\u0000(limitation due to resource constraints and limitation due to large length\u0000instability) for microtubule growth using a stochastic modeling framework. We\u0000show that steady-state analysis of a mean-field model using ordinary\u0000differential equations model aids in parameterizing the stochastic model. This\u0000framework enables investigation of qualitatively different parameter regimes\u0000and provides predictions for both observable and unobservable biological\u0000measurements, such as tubulin allocation and tubulin photoconversion\u0000measurements.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"52 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511043","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