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  1. Book ; Online: Exact lattice-based stochastic cell culture simulation algorithms incorporating spontaneous and contact-dependent reactions

    Boldog, Peter

    2022  

    Abstract: In this paper, we address the modeling issues of cell movement and division with a special focus on the phenomenon of volume exclusion in a lattice-based, exact stochastic simulation framework. We propose a new exact method, called Reduced Rate Method -- ...

    Abstract In this paper, we address the modeling issues of cell movement and division with a special focus on the phenomenon of volume exclusion in a lattice-based, exact stochastic simulation framework. We propose a new exact method, called Reduced Rate Method -- RRM, that is substantially quicker than the previously used exclusion method, for large number of cells. In addition, we introduce three novel reaction types: the contact-inhibited, the contact-promoted, and the spontaneous reactions. To the best of our knowledge, these reaction types have not been taken into account in lattice-based stochastic simulations of cell cultures. These new types of events may be easily applied to complicated systems, enabling the generation of biologically feasible stochastic cell culture simulations. Furthermore, we show that the exclusion algorithm and our RRM algorithm are mathematically equivalent in the sense that the next reaction to be realized and the corresponding sojourn time both belong to the same reaction and time distributions in the two approaches -- even with the newly introduced reaction types. Exact, agent-based, stochastic methods of cell culture simulations seem to be undervalued and are mostly used as benchmarking tools to validate deterministic approximations of the corresponding stochastic models. Our proposed methods are exact, they are easy to implement, have a high predictive value, and can be conveniently extended with new features. Therefore, these approaches promise a great potential.

    Comment: 22 pages, 6 figures
    Keywords Quantitative Biology - Populations and Evolution ; Condensed Matter - Soft Condensed Matter ; Condensed Matter - Statistical Mechanics ; Quantitative Biology - Cell Behavior ; Quantitative Biology - Quantitative Methods ; 92B05 (Primary) ; 92D25 ; 82-10 ; 68Q80 (Secondary)
    Subject code 612
    Publishing date 2022-08-09
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings.

    Meszéna, Domokos / Barlay, Anna / Boldog, Péter / Furuglyás, Kristóf / Cserpán, Dorottya / Wittner, Lucia / Ulbert, István / Somogyvári, Zoltán

    The Journal of physiology

    2023  Volume 601, Issue 15, Page(s) 3351–3376

    Abstract: Although electrophysiologists have been recording intracellular neural activity routinely ever since the ground-breaking work of Hodgkin and Huxley, and extracellular multichannel electrodes have also been used frequently and extensively, a practical ... ...

    Abstract Although electrophysiologists have been recording intracellular neural activity routinely ever since the ground-breaking work of Hodgkin and Huxley, and extracellular multichannel electrodes have also been used frequently and extensively, a practical experimental method to track changes in membrane potential along a complete single neuron is still lacking. Instead of obtaining multiple intracellular measurements on the same neuron, we propose an alternative method by combining single-channel somatic patch-clamp and multichannel extracellular potential recordings. In this work, we show that it is possible to reconstruct the complete spatiotemporal distribution of the membrane potential of a single neuron with the spatial resolution of an extracellular probe during action potential generation. Moreover, the reconstruction of the membrane potential allows us to distinguish between the two major but previously hidden components of the current source density (CSD) distribution: the resistive and the capacitive currents. This distinction provides a clue to the clear interpretation of the CSD analysis, because the resistive component corresponds to transmembrane ionic currents (all the synaptic, voltage-sensitive and passive currents), whereas capacitive currents are considered to be the main contributors of counter-currents. We validate our model-based reconstruction approach on simulations and demonstrate its application to experimental data obtained in vitro via paired extracellular and intracellular recordings from a single pyramidal cell of the rat hippocampus. In perspective, the estimation of the spatial distribution of resistive membrane currents makes it possible to distiguish between active and passive sinks and sources of the CSD map and the localization of the synaptic input currents, which make the neuron fire. KEY POINTS: A new computational method is introduced to calculate the unbiased current source density distribution on a single neuron with known morphology. The relationship between extracellular and intracellular electric potential is determined via mathematical formalism, and a new reconstruction method is applied to reveal the full spatiotemporal distribution of the membrane potential and the resistive and capacitive current components. The new reconstruction method was validated on simulations. Simultaneous and colocalized whole-cell patch-clamp and multichannel silicon probe recordings were performed from the same pyramidal neuron in the rat hippocampal CA1 region, in vitro. The method was applied in experimental measurements and returned precise and distinctive characteristics of various intracellular phenomena, such as action potential generation, signal back-propagation and the initial dendritic depolarization preceding the somatic action potential.
    MeSH term(s) Rats ; Animals ; Membrane Potentials/physiology ; Neurons/physiology ; Pyramidal Cells/physiology ; Action Potentials ; Hippocampus/physiology
    Language English
    Publishing date 2023-01-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP283550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: Propensity matrix method for age dependent stochastic infectious disease models

    Boldog, Péter / Bogya, Norbert / Vizi, Zsolt

    2021  

    Abstract: Mathematical modeling is one of the key factors of the effective control of newly found infectious diseases, such as COVID-19. Our knowledge about the parameters and the course of the infection is highly limited in the beginning of the epidemic, hence ... ...

    Abstract Mathematical modeling is one of the key factors of the effective control of newly found infectious diseases, such as COVID-19. Our knowledge about the parameters and the course of the infection is highly limited in the beginning of the epidemic, hence computer implementation of the models have to be quick and flexible. The propensity matrix - update graph method we discuss in this paper serves as a convenient approach to efficiently implement age structured stochastic epidemic models. The code base we implemented for our forecasting work is also included in the attached GitHub repository.
    Keywords Quantitative Biology - Quantitative Methods ; Mathematics - Probability ; Quantitative Biology - Populations and Evolution
    Publishing date 2021-10-10
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China.

    Boldog, Péter / Tekeli, Tamás / Vizi, Zsolt / Dénes, Attila / Bartha, Ferenc A / Röst, Gergely

    Journal of clinical medicine

    2020  Volume 9, Issue 2

    Abstract: We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the ... ...

    Abstract We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.
    Keywords covid19
    Language English
    Publishing date 2020-02-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9020571
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  5. Book ; Online: Convergence of solutions in a mean-field model of go-or-grow type with reservation of sites for proliferation and cell cycle delay

    Baker, Ruth E. / Boldog, Péter / Röst, Gergely

    2019  

    Abstract: We consider the mean-field approximation of an individual-based model describing cell motility and proliferation, which incorporates the volume exclusion principle, the go-or-grow hypothesis and an explicit cell cycle delay. To utilise the framework of ... ...

    Abstract We consider the mean-field approximation of an individual-based model describing cell motility and proliferation, which incorporates the volume exclusion principle, the go-or-grow hypothesis and an explicit cell cycle delay. To utilise the framework of on-lattice agent-based models, we make the assumption that cells enter mitosis only if they can secure an additional site for the daughter cell, in which case they occupy two lattice sites until the completion of mitosis. The mean-field model is expressed by a system of delay differential equations and includes variables such as the number of motile cells, proliferating cells, reserved sites and empty sites. We prove the convergence of biologically feasible solutions: eventually all available space will be filled by mobile cells, after an initial phase when the proliferating cell population is increasing then diminishing. By comparing the behaviour of the mean-field model for different parameter values and initial cell distributions, we illustrate that the total cell population may follow a logistic-type growth curve, or may grow in a step-function-like fashion.
    Keywords Quantitative Biology - Cell Behavior
    Subject code 612
    Publishing date 2019-03-03
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Potential severity, mitigation, and control of Omicron waves depending on pre-existing immunity and immune evasion

    Bartha, Ferenc A. / Boldog, Péter / Dénes, Attila / Tekeli, Tamás / Vizi, Zsolt / Röst, Gergely

    medRxiv

    Abstract: We assess the potential consequences of the upcoming SARS-CoV-2 waves caused by the Omicron variant. Our results suggest that even in those regions where the Delta variant is controlled at the moment by a combination of non-pharmaceutical interventions ... ...

    Abstract We assess the potential consequences of the upcoming SARS-CoV-2 waves caused by the Omicron variant. Our results suggest that even in those regions where the Delta variant is controlled at the moment by a combination of non-pharmaceutical interventions and population immunity, a significant Omicron wave can be expected. We stratify the population according to prior immunity status, and characterize the possible outbreaks depending on the population level of pre-existing immunity and the immune evasion capability of Omicron. We point out that two countries having similar effective reproduction numbers for the Delta variant can experience very different Omicron waves in terms of peak time, peak size and total number of infections among the high risk population.
    Keywords covid19
    Language English
    Publishing date 2021-12-16
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.12.15.21267884
    Database COVID19

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  7. Book ; Online: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China

    Péter Boldog / Tamás Tekeli / Zsolt Vizi / Attila Dénes / Ferenc A. Bartha / Gergely Röst

    Journal of Clinical Medicine ; Volume 9 ; Issue 2

    2020  

    Abstract: We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the ... ...

    Abstract We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas

    (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination

    and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.
    Keywords novel coronavirus ; transmission ; risk assessment ; interventions ; travel ; outbreak ; COVID-19 ; compartmental model ; branching process ; covid19
    Subject code 950
    Language English
    Publishing date 2020-02-19
    Publisher Multidisciplinary Digital Publishing Institute
    Publishing country ch
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China

    Péter Boldog / Tamás Tekeli / Zsolt Vizi / Attila Dénes / Ferenc A. Bartha / Gergely Röst

    Journal of Clinical Medicine, Vol 9, Iss 2, p

    2020  Volume 571

    Abstract: We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the ... ...

    Abstract We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number <math display="inline"> <semantics> <msub> <mi>R</mi> <mi>loc</mi> </msub> </semantics> </math> ). We found that in countries with low connectivity to China but with relatively high <math display="inline"> <semantics> <msub> <mi>R</mi> <mi>loc</mi> </msub> </semantics> </math> , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low <math display="inline"> <semantics> <msub> <mi>R</mi> <mi>loc</mi> </msub> </semantics> </math> benefit the most from policies that further reduce <math display="inline"> <semantics> <msub> <mi>R</mi> <mi>loc</mi> </msub> </semantics> </math> . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.
    Keywords novel coronavirus ; transmission ; risk assessment ; interventions ; travel ; outbreak ; covid-19 ; compartmental model ; branching process ; Medicine ; R ; covid19
    Subject code 511
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Risk assessment of novel coronavirus COVID-19 outbreaks outside China

    Boldog, Péter / Tekeli, Tamás / Vizi, Zsolt / Dénes, Attila / Bartha, Ferenc Ágoston / Röst, Gergely

    2020  

    Keywords covid19
    Language English
    Publishing country hu
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Risk assessment of novel coronavirus COVID-19 outbreaks outside China

    Boldog, Peter / Tekeli, Tamas / Vizi, Zsolt / Denes, Attila / Bartha, Ferenc / Rost, Gergely

    medRxiv

    Keywords covid19
    Language English
    Publishing date 2020-02-27
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.02.04.20020503
    Database COVID19

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