In Silico Biology最新文献_第2页

Moonlighting proteins - an approach to systematize the concept. 兼职蛋白质-一种系统化概念的方法。

In Silico Biology Pub Date : 2020-01-01 DOI: 10.3233/ISB-190473

Maria Krantz, Edda Klipp

{"title":"Moonlighting proteins - an approach to systematize the concept.","authors":"Maria Krantz, Edda Klipp","doi":"10.3233/ISB-190473","DOIUrl":"https://doi.org/10.3233/ISB-190473","url":null,"abstract":"Moonlighting refers to a protein with at least two unrelated, mechanistically different functions. As a concept, moonlighting describes a large and diverse group of proteins which have been discovered in a multitude of organisms. As of today, a systematized view on these proteins is missing. Here, we propose a classification of moonlighting proteins by two classifiers. We use the function of the protein as a first classifier: activating - activating (Type I), activating - inhibiting (Type II), inhibiting - activating (Type III) and inhibiting - inhibiting (Type IV). To further specify the type of moonlighting protein, we used a second classifier based on the character of the factor that switches the function of the protein: external factor affecting the protein (Type A), change in the first pathway (Type B), change in the second pathway (Type C), equal competition between both pathways (Type D). Using a small two-pathway model we simulated these types of moonlighting proteins to elucidate possible behaviors of the types of moonlighting proteins. We find that, using the results of our simulations, we can classify the behavior of the moonlighting types into Blinker, Splitter andSwitch.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-190473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37829807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

A computational model of bidirectional axonal growth in micro-tissue engineered neuronal networks (micro-TENNs). 微组织工程神经元网络（micro-TENNs）中轴突双向生长的计算模型。

In Silico Biology Pub Date : 2020-01-01 DOI: 10.3233/ISB-180172

Toma Marinov, Haven A López Sánchez, Liang Yuchi, Dayo O Adewole, D Kacy Cullen, Reuben H Kraft

{"title":"A computational model of bidirectional axonal growth in micro-tissue engineered neuronal networks (micro-TENNs).","authors":"Toma Marinov, Haven A López Sánchez, Liang Yuchi, Dayo O Adewole, D Kacy Cullen, Reuben H Kraft","doi":"10.3233/ISB-180172","DOIUrl":"10.3233/ISB-180172","url":null,"abstract":"Micro-Tissue Engineered Neural Networks (Micro-TENNs) are living three-dimensional constructs designed to replicate the neuroanatomy of white matter pathways in the brain and are being developed as implantable micro-tissue for axon tract reconstruction, or as anatomically-relevant in vitro experimental platforms. Micro-TENNs are composed of discrete neuronal aggregates connected by bundles of long-projecting axonal tracts within miniature tubular hydrogels. In order to help design and optimize micro-TENN performance, we have created a new computational model including geometric and functional properties. The model is built upon the three-dimensional diffusion equation and incorporates large-scale uni- and bi-directional growth that simulates realistic neuron morphologies. The model captures unique features of 3D axonal tract development that are not apparent in planar outgrowth and may be insightful for how white matter pathways form during brain development. The processes of axonal outgrowth, branching, turning and aggregation/bundling from each neuron are described through functions built on concentration equations and growth time distributed across the growth segments. Once developed we conducted multiple parametric studies to explore the applicability of the method and conducted preliminary validation via comparisons to experimentally grown micro-TENNs for a range of growth conditions. Using this framework, the model can be applied to study micro-TENN growth processes and functional characteristics using spiking network or compartmental network modeling. This model may be applied to improve our understanding of axonal tract development and functionality, as well as to optimize the fabrication of implantable tissue engineered brain pathways for nervous system reconstruction and/or modulation.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/bb/isb-13-isb180172.PMC7505002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37921296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A hybrid multiscale model for investigating tumor angiogenesis and its response to cell-based therapy. 研究肿瘤血管生成及其对细胞治疗反应的混合多尺度模型。

In Silico Biology Pub Date : 2019-01-01 DOI: 10.3233/ISB-170469

Melisa Hendrata, Janti Sudiono

{"title":"A hybrid multiscale model for investigating tumor angiogenesis and its response to cell-based therapy.","authors":"Melisa Hendrata, Janti Sudiono","doi":"10.3233/ISB-170469","DOIUrl":"https://doi.org/10.3233/ISB-170469","url":null,"abstract":"Angiogenesis, a formation of blood vessels from an existing vasculature, plays a key role in tumor growth and its progression into cancer. The lining of blood vessels consists of endothelial cells (ECs) which proliferate and migrate, allowing the capillaries to sprout towards the tumor to deliver the needed oxygen. Various treatments aiming to suppress or even inhibit angiogenesis have been explored. Mesenchymal stem cells (MSCs) have recently been undergoing development in cell-based therapy for cancer due to their ability to migrate towards the capillaries and induce the apoptosis of the ECs, causing capillary degeneration. However, further investigations in this direction are needed as it is usually difficult to preclinically assess the efficacy of such therapy. We develop a hybrid multiscale model that integrates molecular, cellular, tissue and extracellular components of tumor system to investigate angiogenesis and tumor growth under MSC-mediated therapy. Our simulations produce angiogenesis and vascular tumor growth profiles as observed in the experiments. Furthermore, the simulations show that the effectiveness of MSCs in inducing EC apoptosis is density dependent and its full effect is reached within several days after MSCs application. Quantitative agreements with experimental data indicate the predictive potential of our model for evaluating the efficacy of cell-based therapies targeting angiogenesis.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-170469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35239545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Modeling cell population dynamics. 细胞群体动力学建模。

In Silico Biology Pub Date : 2019-01-01 DOI: 10.3233/ISB-180470

Daniel A Charlebois, Gábor Balázsi

引用次数: 44

Lower connectivity of tumor coexpression networks is not specific to cancer. 肿瘤共表达网络的低连通性并不是癌症特有的。

In Silico Biology Pub Date : 2019-01-01 DOI: 10.3233/ISB-190472

Ertuğrul Dalgıç, Özlen Konu, Zehra Safi Öz, Christina Chan

{"title":"Lower connectivity of tumor coexpression networks is not specific to cancer.","authors":"Ertuğrul Dalgıç, Özlen Konu, Zehra Safi Öz, Christina Chan","doi":"10.3233/ISB-190472","DOIUrl":"https://doi.org/10.3233/ISB-190472","url":null,"abstract":"Global level network analysis of molecular links is necessary for systems level view of complex diseases like cancer. Using genome-wide expression datasets, we constructed and compared gene co-expression based specific networks of pre-cancerous tumors (adenoma) and cancerous tumors (carcinoma) with paired normal networks to assess for any possible changes in network connectivity. Previously, loss of connectivity was reported as a characteristics of cancer samples. Here, we observed that pre-cancerous conditions also had significantly less connections than paired normal samples. We observed a loss of connectivity trend for colorectal adenoma, aldosterone producing adenoma and uterine leiomyoma. We also showed that the loss of connectivity trend is not specific to positive or negative correlation based networks. Differential hub genes, which were the most highly differentially less connected genes in tumor, were mostly different between different datasets. No common gene list could be defined which underlies the lower connectivity of tumor specific networks. Connectivity of colorectal cancer methylation targets was different from other genes. Extracellular space related terms were enriched in negative correlation based differential hubs and common methylation targets of colorectal carcinoma. Our results indicate a systems level change of lower connectivity as cells transform to not only cancer but also pre-cancerous conditions. This systems level behavior could not be attributed to a group of genes.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-190472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37301274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Calibration, Selection and Identifiability Analysis of a Mathematical Model of the in vitro Erythropoiesis in Normal and Perturbed Contexts. 正常和扰动条件下体外红细胞生成数学模型的校准、选择和可识别性分析。

In Silico Biology Pub Date : 2019-01-01 DOI: 10.3233/ISB-190471

Ronan Duchesne, Anissa Guillemin, Fabien Crauste, Olivier Gandrillon

{"title":"Calibration, Selection and Identifiability Analysis of a Mathematical Model of the in vitro Erythropoiesis in Normal and Perturbed Contexts.","authors":"Ronan Duchesne, Anissa Guillemin, Fabien Crauste, Olivier Gandrillon","doi":"10.3233/ISB-190471","DOIUrl":"https://doi.org/10.3233/ISB-190471","url":null,"abstract":"The in vivo erythropoiesis, which is the generation of mature red blood cells in the bone marrow of whole organisms, has been described by a variety of mathematical models in the past decades. However, the in vitro erythropoiesis, which produces red blood cells in cultures, has received much less attention from the modelling community. In this paper, we propose the first mathematical model of in vitro erythropoiesis. We start by formulating different models and select the best one at fitting experimental data of in vitro erythropoietic differentiation obtained from chicken erythroid progenitor cells. It is based on a set of linear ODE, describing 3 hypothetical populations of cells at different stages of differentiation. We then compute confidence intervals for all of its parameters estimates, and conclude that our model is fully identifiable. Finally, we use this model to compute the effect of a chemical drug called Rapamycin, which affects all states of differentiation in the culture, and relate these effects to specific parameter variations. We provide the first model for the kinetics of in vitro cellular differentiation which is proven to be identifiable. It will serve as a basis for a model which will better account for the variability which is inherent to the experimental protocol used for the model calibration.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-190471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37172496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calibration, Selection and Identifiability Analysis of a Mathematical Model of the in vitro Erythropoiesis in Normal and Perturbed Contexts 正常和扰动条件下体外红细胞生成数学模型的校准、选择和可识别性分析

In Silico Biology Pub Date : 2018-05-05 DOI: 10.1101/314955

Ronan Duchesne, Anissa Guillemin, F. Crauste, O. Gandrillon

{"title":"Calibration, Selection and Identifiability Analysis of a Mathematical Model of the in vitro Erythropoiesis in Normal and Perturbed Contexts","authors":"Ronan Duchesne, Anissa Guillemin, F. Crauste, O. Gandrillon","doi":"10.1101/314955","DOIUrl":"https://doi.org/10.1101/314955","url":null,"abstract":"The in vivo erythropoiesis, which is the generation of mature red blood cells in the bone marrow of whole organisms, has been described by a variety of mathematical models in the past decades. However, the in vitro erythropoiesis, which produces red blood cells in cultures, has received much less attention from the modelling community. In this paper, we propose the first mathematical model of in vitro erythropoiesis. We start by formulating different models and select the best one at fitting experimental data of in vitro erythropoietic differentiation. It is based on a set of linear ODE, describing 3 hypothetical populations of cells at different stages of differentiation. We then compute confidence intervals for all of its parameters estimates, and conclude that our model is fully identifiable. Finally, we use this model to compute the effect of a chemical drug called Rapamycin, which affects all states of differentiation in the culture, and relate these effects to specific parameter variations. We provide the first model for the kinetics of in vitro cellular differentiation which is proven to be identifiable. It will serve as a basis for a model which will better account for the variability which is inherent to experimental protocol used for the model calibration.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43637124","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: 6

Differential transcriptional regulation by alternatively designed mechanisms: A mathematical modeling approach. 不同设计机制的差异转录调控:数学建模方法。

In Silico Biology Pub Date : 2017-01-01 DOI: 10.3233/ISB-160467

Necmettin Yildirim, Mehmet Emin Aktas, Seyma Nur Ozcan, Esra Akbas, Ahmet Ay

{"title":"Differential transcriptional regulation by alternatively designed mechanisms: A mathematical modeling approach.","authors":"Necmettin Yildirim, Mehmet Emin Aktas, Seyma Nur Ozcan, Esra Akbas, Ahmet Ay","doi":"10.3233/ISB-160467","DOIUrl":"https://doi.org/10.3233/ISB-160467","url":null,"abstract":"Cells maintain cellular homeostasis employing different regulatory mechanisms to respond external stimuli. We study two groups of signal-dependent transcriptional regulatory mechanisms. In the first group, we assume that repressor and activator proteins compete for binding to the same regulatory site on DNA (competitive mechanisms). In the second group, they can bind to different regulatory regions in a noncompetitive fashion (noncompetitive mechanisms). For both competitive and noncompetitive mechanisms, we studied the gene expression dynamics by increasing the repressor or decreasing the activator abundance (inhibition mechanisms), or by decreasing the repressor or increasing the activator abundance (activation mechanisms). We employed delay differential equation models. Our simulation results show that the competitive and noncompetitive inhibition mechanisms exhibit comparable repression effectiveness. However, response time is fastest in the noncompetitive inhibition mechanism due to increased repressor abundance, and slowest in the competitive inhibition mechanism by increased repressor level. The competitive and noncompetitive inhibition mechanisms through decreased activator abundance show comparable and moderate response times, while the competitive and noncompetitive activation mechanisms by increased activator protein level display more effective and faster response. Our study exemplifies the importance of mathematical modeling and computer simulation in the analysis of gene expression dynamics.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-160467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34628179","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: 1

Cellular automata model for human articular chondrocytes migration, proliferation and cell death: An in vitro validation 人关节软骨细胞迁移、增殖和细胞死亡的细胞自动机模型:体外验证

In Silico Biology Pub Date : 2017-01-01 DOI: 10.3233/ISB-150466

J. J. Vaca-González, M. L. Gutiérrez, J. Guevara, D. Garzón-Alvarado

{"title":"Cellular automata model for human articular chondrocytes migration, proliferation and cell death: An in vitro validation","authors":"J. J. Vaca-González, M. L. Gutiérrez, J. Guevara, D. Garzón-Alvarado","doi":"10.3233/ISB-150466","DOIUrl":"https://doi.org/10.3233/ISB-150466","url":null,"abstract":"Articular cartilage is characterized by low cell density of only one cell type, chondrocytes, and has limited self-healing properties. When articular cartilage is affected by traumatic injuries, a therapeutic strategy such as autologous chondrocyte implantation is usually proposed for its treatment. This approach requires in vitro chondrocyte expansion to yield high cell number for cell transplantation. To improve the efficiency of this procedure, it is necessary to assess cell dynamics such as migration, proliferation and cell death during culture. Computational models such as cellular automata can be used to simulate cell dynamics in order to enhance the result of cell culture procedures. This methodology has been implemented for several cell types; however, an experimental validation is required for each one. For this reason, in this research a cellular automata model, based on random-walk theory, was devised in order to predict articular chondrocyte behavior in monolayer culture during cell expansion. Results demonstrated that the cellular automata model corresponded to cell dynamics and computed-accurate quantitative results. Moreover, it was possible to observe that cell dynamics depend on weighted probabilities derived from experimental data and cell behavior varies according to the cell culture period. Thus, depending on whether cells were just seeded or proliferated exponentially, culture time probabilities differed in percentages in the CA model. Furthermore, in the experimental assessment a decreased chondrocyte proliferation was observed along with increased passage number. This approach is expected to having other uses as in enhancing articular cartilage therapies based on tissue engineering and regenerative medicine.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-150466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69960308","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: 4

Limits of computational biology. 计算生物学的极限。

In Silico Biology Pub Date : 2015-01-01 DOI: 10.3233/ISB-140461

Dennis Bray

{"title":"Limits of computational biology.","authors":"Dennis Bray","doi":"10.3233/ISB-140461","DOIUrl":"https://doi.org/10.3233/ISB-140461","url":null,"abstract":"Are we close to a complete inventory of living processes so that we might expect in the near future to reproduce every essential aspect necessary for life? Or are there mechanisms and processes in cells and organisms that are presently inaccessible to us? Here I argue that a close examination of a particularly well-understood system--that of Escherichia coli chemotaxis--shows we are still a long way from a complete description. There is a level of molecular uncertainty, particularly that responsible for fine-tuning and adaptation to myriad external conditions, which we presently cannot resolve or reproduce on a computer. Moreover, the same uncertainty exists for any process in any organism and is especially pronounced and important in higher animals such as humans. Embryonic development, tissue homeostasis, immune recognition, memory formation, and survival in the real world, all depend on vast numbers of subtle variations in cell chemistry most of which are presently unknown or only poorly characterized. Overcoming these limitations will require us to not only accumulate large quantities of highly detailed data but also develop new computational methods able to recapitulate the massively parallel processing of living cells.","PeriodicalId":39379,"journal":{"name":"In Silico Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/ISB-140461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32748919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8