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Michael Meyer-Hermann

Publications and source records attributed to Michael Meyer-Hermann.

At least 19 recordsLinked to original sources

MEmilio -- A high performance Modular EpideMIcs simuLatIOn software for multi-scale and comparative simulations of infectious disease dynamics

Epidemic and pandemic preparedness with rapid outbreak response rely on timely, trustworthy evidence. Mathematical models are crucial for supporting timely and reliable evidence generation for public health decision-making with models spanning approaches from compartmental and metapopulation models to detailed agent-based simulations. Yet, the accompanying software ecosystem remains fragmented across model types, spatial resolutions, and computational targets, making models harder to compare, extend, and deploy at scale. Here we present MEmilio, a modular, high-performance framework for epidemic simulation that harmonizes the specification and execution of diverse dynamic epidemiological models within a unified and harmonized architecture. MEmilio couples an efficient C++ simulation core with coherent model descriptions and a user-friendly Python interface, enabling workflows that run on laptops as well as high-performance computing systems. Standardized representations of space, demography, and mobility support straightforward adaptations in resolution and population size, facilitating systematic inter-model comparisons and ensemble studies. The framework integrates readily with established tools for uncertainty quantification and parameter inference, supporting a broad range of applications from scenario exploration to calibration. Finally, strict software-engineering practices, including extensive unit and continuous integration testing, promote robustness and minimize the risk of errors as the framework evolves. By unifying implementations across modeling paradigms, MEmilio aims to lower barriers to reuse and generalize models, enable principled comparisons of implicit assumptions, and accelerate the development of novel approaches that strengthen modeling-based outbreak preparedness.

q-bio.PE

A full software stack for epidemic disease management: Unlocking the joint potential of software technology and supercomputing

Infectious diseases remain a major threat to human societies. During the recent COVID-19 pandemic, mathematical modeling and extensive computer simulations proved highly effective in supporting public health experts and decision makers. Despite these advances, the full potential of modern modeling approaches and digital technologies has not yet been realized. Many critical tasks -- including expert consultations, model execution, scenario analyses, report preparation, and result communication -- still relied heavily on manual, human-driven processes with each manual interaction introducing avoidable delays and limiting responsiveness during rapidly evolving outbreaks. Pandemic preparedness should opt for automated workflows and seamlessly integrated software modules that can improve pandemic mitigation capabilities by substantially reducing response times. For this step, we require robust and flexible computational infrastructure capable of supporting heterogeneous hardware and continuously evolving infectious-disease models. In addition, data sources need to be dynamically integrated. Managing such demands needs infrastructure that supports automated high-performance computing (HPC) workflows. Beyond computational performance, software infrastructure must ensure secure user and data management to comply with data-protection regulations and provide clear, transparent presentation of results to both decision makers and the public. Meeting the aforementioned challenges requires tight integration of state-of-the-art scientific software with modern, scalable infrastructure that can leverage supercomputing resources when necessary. For rapid deployment in future epidemic or pandemic scenarios, adherence to the FAIR principles for research software is critical to ensure reusability and sustainability.

cs.CE

Agent-based modeling for realistic reproduction of human mobility and contact behavior to evaluate test and isolation strategies in epidemic infectious disease spread

Agent-based models have proven to be useful tools in supporting decision-making processes in different application domains. The advent of modern computers and supercomputers has enabled these bottom-up approaches to realistically model human mobility and contact behavior. The COVID-19 pandemic showcased the urgent need for detailed and informative models that can answer research questions on transmission dynamics. We present a sophisticated agent-based model to simulate the spread of respiratory diseases. The model is highly modularized and can be used on various scales, from a small collection of buildings up to cities or countries. Although not being the focus of this paper, the model has undergone performance engineering on a single core and provides an efficient intra- and inter-simulation parallelization for time-critical decision-making processes. In order to allow answering research questions on individual level resolution, nonpharmaceutical intervention strategies such as face masks or venue closures can be implemented for particular locations or agents. In particular, we allow for sophisticated testing and isolation strategies to study the effects of minimal-invasive infectious disease mitigation. With realistic human mobility patterns for the region of Brunswick, Germany, we study the effects of different interventions between March 1st and May 30, 2021 in the SARS-CoV-2 pandemic. Our analyses suggest that symptom-independent testing has limited impact on the mitigation of disease dynamics if the dark figure in symptomatic cases is high. Furthermore, we found that quarantine length is more important than quarantine efficiency but that, with sufficient symptomatic control, also short quarantines can have a substantial effect.

cs.MA

Hybrid metapopulation agent-based epidemiological models for efficient insight on the individual scale: a contribution to green computing

Emerging infectious diseases and climate change are two of the major challenges in 21st century. Although over the past decades, highly-resolved mathematical models have contributed in understanding dynamics of infectious diseases and are of great aid when it comes to finding suitable intervention measures, they may need substantial computational effort and produce significant CO2 emissions. Two popular modeling approaches for mitigating infectious disease dynamics are agent-based and population-based models. Agent-based models (ABMs) offer a microscopic view and are thus able to capture heterogeneous human contact behavior and mobility patterns. However, insights on individual-level dynamics come with high computational effort that scales with the number of agents. On the other hand, population-based models using e.g. ordinary differential equations (ODEs) are computationally efficient even for large populations due to their complexity being independent of the population size. Yet, population-based models are restricted in their granularity as they assume a (to some extent) homogeneous and well-mixed population. To manage the trade-off between computational complexity and level of detail, we propose spatial- and temporal-hybrid models that use ABMs only in an area or time frame of interest. To account for relevant influences to disease dynamics, e.g., from outside, due to commuting activities, we use population-based models, only adding moderate computational costs. Our hybridization approach demonstrates significant reduction in computational effort by up to 98% -- without losing the required depth in information in the focus frame. Concluding, hybrid epidemiological models can provide insights on the individual scale where necessary, using aggregated models where possible, thereby making a contribution to green computing.

q-bio.PE

ESID: Exploring the Design and Development of a Visual Analytics Tool for Epidemiological Emergencies

Visual analytics tools can help illustrate the spread of infectious diseases and enable informed decisions on epidemiological and public health issues. To create visualisation tools that are intuitive, easy to use, and effective in communicating information, continued research and development focusing on user-centric and methodological design models is extremely important. As a contribution to this topic, this paper presents the design and development process of the visual analytics application ESID (Epidemiological Scenarios for Infectious Diseases). ESID is a visual analytics tool aimed at projecting the future developments of infectious disease spread using reported and simulated data based on sound mathematical-epidemiological models. The development process involved a collaborative and participatory design approach with project partners from diverse scientific fields. The findings from these studies, along with the guidelines derived from them, played a pivotal role in shaping the visualisation tool.

cs.HC

Inferring the effect of interventions on COVID-19 transmission networks

Countries around the world implement nonpharmaceutical interventions (NPIs) to mitigate the spread of COVID-19. Design of efficient NPIs requires identification of the structure of the disease transmission network. We here identify the key parameters of the COVID-19 transmission network for time periods before, during, and after the application of strict NPIs for the first wave of COVID-19 infections in Germany combining Bayesian parameter inference with an agent-based epidemiological model. We assume a Watts-Strogatz small-world network which allows to distinguish contacts within clustered cliques and unclustered, random contacts in the population, which have been shown to be crucial in sustaining the epidemic. In contrast to other works, which use coarse-grained network structures from anonymized data, like cell phone data, we consider the contacts of individual agents explicitly. We show that NPIs drastically reduced random contacts in the transmission network, increased network clustering, and resulted in a change from an exponential to a constant regime of newcases. In this regime, the disease spreads like a wave with a finite wave speed that depends on the number of contacts in a nonlinear fashion, which we can predict by mean field theory. Our analysis indicates that besides the well-known transitionbetween exponential increase and exponential decrease in the number of new cases, NPIs can induce a transition to another, previously unappreciated regime of constant new cases.

q-bio.PE

Potential benefits of delaying the second mRNA COVID-19 vaccine dose

Vaccination against COVID-19 with the recently approved mRNA vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) is currently underway in a large number of countries. However, high incidence rates and rapidly spreading SARS-CoV-2 variants are concerning. In combination with acute supply deficits in Europe in early 2021, the question arises of whether stretching the vaccine, for instance by delaying the second dose, can make a significant contribution to preventing deaths, despite associated risks such as lower vaccine efficacy, the potential emergence of escape mutants, enhancement, waning immunity, reduced social acceptance of off-label vaccination, and liability shifts. A quantitative epidemiological assessment of risks and benefits of non-standard vaccination protocols remains elusive. To clarify the situation and to provide a quantitative epidemiological foundation we develop a stochastic epidemiological model that integrates specific vaccine rollout protocols into a risk-group structured infectious disease dynamical model. Using the situation and conditions in Germany as a reference system, we show that delaying the second vaccine dose is expected to prevent deaths in the four to five digit range, should the incidence resurge. We show that this considerable public health benefit relies on the fact that both mRNA vaccines provide substantial protection against severe COVID-19 and death beginning 12 to 14 days after the first dose. The benefits of protocol change are attenuated should vaccine compliance decrease substantially. To quantify the impact of protocol change on vaccination adherence we performed a large-scale online survey. We find that, in Germany, changing vaccination protocols may lead to small reductions in vaccination intention. In sum, we therefore expect the benefits of a strategy change to remain substantial and stable.

q-bio.PE

The foreshadow of a second wave: An analysis of current COVID-19 fatalities in Germany

A second wave of SARS-CoV-2 is unfolding in dozens of countries. However, this second wave manifests itself strongly in new reported cases, but less in death counts compared to the first wave. Over the past three months in Germany, the reported cases increased by a factor five or more, whereas the death counts hardly grew. This discrepancy fueled speculations that the rise of reported cases would not reflect a second wave but only wider testing. We find that this apparent discrepancy can be explained to a large extent by the age structure of the infected, and predict a pronounced increase of death counts in the near future, as the spread once again expands into older age groups. To re-establish control, and to avoid the tipping point when TTI capacity is exceeded, case numbers have to be lowered. Otherwise the control of the spread and the protection of vulnerable people will require more restrictive measures latest when the hospital capacity is reached.

q-bio.PE

Entropy-driven cell-decision making predicts fluid-to-solid transition in multicellular systems

Cellular decision making allows cells to assume functionally different phenotypes in response to microenvironmental cues, without genetic change. It is an open question, how individual cell decisions influence the dynamics at the tissue level. Here, we study spatio-temporal pattern formation in a population of cells exhibiting phenotypic plasticity, which is a paradigm of cell decision making. We focus on the migration/resting and the migration/proliferation plasticity which underly the epithelial-mesenchymal transition (EMT) and the go or grow dichotomy. We assume that cells change their phenotype in order to minimize their microenvironmental entropy (LEUP: Least microEnvironmental Uncertainty Principle) and study the impact of the LEUP-driven migration/resting and migration/proliferation plasticity on the corresponding multicellular spatio-temporal dynamics with a stochastic cell-based mathematical model for the spatio-temporal dynamics of the cell phenotypes. In the case of the go or rest plasticity, a corresponding mean-field approximation allows to identify a bistable switching mechanism between a diffusive (fluid) and an epithelial (solid) tissue phase which depends on the sensitivity of the phenotypes to the environment. For the go or grow plasticity, we show the possibility of Turing pattern formation for the "solid" tissue phase and its relation with the parameters of the LEUP-driven cell decisions.

physics.bio-ph

Avian photoreceptor patterns represent a disordered hyperuniform solution to a multiscale packing problem

Optimal spatial sampling of light rigorously requires that identical photoreceptors be arranged in perfectly regular arrays in two dimensions. Examples of such perfect arrays in nature include the compound eyes of insects and the nearly crystalline photoreceptor patterns of some fish and reptiles. Birds are highly visual animals with five different cone photoreceptor subtypes, yet their photoreceptor patterns are not perfectly regular. By analyzing the chicken cone photoreceptor system consisting of five different cell types using a variety of sensitive microstructural descriptors, we find that the disordered photoreceptor patterns are ``hyperuniform'' (exhibiting vanishing infinite-wavelength density fluctuations), a property that had heretofore been identified in a unique subset of physical systems, but had never been observed in any living organism. Remarkably, the photoreceptor patterns of both the total population and the individual cell types are simultaneously hyperuniform. We term such patterns ``multi-hyperuniform'' because multiple distinct subsets of the overall point pattern are themselves hyperuniform. We have devised a unique multiscale cell packing model in two dimensions that suggests that photoreceptor types interact with both short- and long-ranged repulsive forces and that the resultant competition between the types gives rise to the aforementioned singular spatial features characterizing the system, including multi-hyperuniformity.

cond-mat.stat-mech

Modeling emergent tissue organization involving high-speed migrating cells in a flow equilibrium

There is increasing interest in the analysis of biological tissue, its organization and its dynamics with the help of mathematical models. In the ideal case emergent properties on the tissue scale can be derived from the cellular scale. However, this has been achieved in rare examples only, in particular, when involving high-speed migration of cells. One major difficulty is the lack of a suitable multiscale simulation platform, which embeds reaction-diffusion of soluble substances, fast cell migration and mechanics, and, being of great importance in several tissue types, cell flow homeostasis. In this paper a step into this direction is presented by developing an agent-based mathematical model specifically designed to incorporate these features with special emphasis on high speed cell migration. Cells are represented as elastic spheres migrating on a substrate in lattice-free space. Their movement is regulated and guided by chemoattractants that can be derived from the substrate. The diffusion of chemoattractants is considered to be slower than cell migration and, thus, to be far from equilibrium. Tissue homeostasis is not achieved by the balance of growth and death but by a flow equilibrium of cells migrating in and out of the tissue under consideration. In this sense the number and the distribution of the cells in the tissue is a result of the model and not part of the assumptions. For purpose of demonstration of the model properties and functioning, the model is applied to a prominent example of tissue in a cellular flow equilibrium, the secondary lymphoid tissue. The experimental data on cell speed distributions in these tissues can be reproduced using reasonable mechanical parameters for the simulated cell migration in dense tissue.

q-bio.TO

A modelling approach towards Epidermal homoeostasis control

In order to grasp the features arising from cellular discreteness and individuality, in large parts of cell tissue modelling agent-based models are favoured. The subclass of off-lattice models allows for a physical motivation of the intercellular interaction rules. We apply an improved version of a previously introduced off-lattice agent-based model to the steady-state flow equilibrium of skin. The dynamics of cells is determined by conservative and drag forces,supplemented with delta-correlated random forces. Cellular adjacency is detected by a weighted Delaunay triangulation. The cell cycle time of keratinocytes is controlled by a diffusible substance provided by the dermis. Its concentration is calculated from a diffusion equation with time-dependent boundary conditions and varying diffusion coefficients. The dynamics of a nutrient is also taken into account by a reaction-diffusion equation. It turns out that the analysed control mechanism suffices to explain several characteristics of epidermal homoeostasis formation. In addition, we examine the question of how {\em in silico} melanoma with decreased basal adhesion manage to persist within the steady-state flow-equilibrium of the skin.Interestingly, even for melanocyte cell cycle times being substantially shorter than for keratinocytes, tiny stochastic effects can lead to completely different outcomes. The results demonstrate that the understanding of initial states of tumour growth can profit significantly from the application of off-lattice agent-based models in computer simulations.

physics.bio-ph

The electrophysiology of the betacell based on single transmembrane protein characteristics

The electrophysiology of betacells is at the origin of insulin secretion. Betacells exhibit a complex behaviour upon stimulation with glucose including repeated and uninterrupted bursting. Mathematical modelling is most suitable to improve knowledge about the function of various transmembrane currents provided the model is based on reliable data. This is the first attempt to build a mathematical model for the betacell-electrophysiology in a bottom-up approach which relies on single protein conductivity data. The results of previous whole-cell-based models are reconsidered. The full simulation including all prominent transmembrane proteins in betacells is used to provide a functional interpretation of their role in betacell-bursting and an updated vantage point of betacell-electrophysiology. As a result of a number of in silico knock-out- and block-experiments the novel model makes some unexpected predictions: Single-channel conductivity data imply that calcium-gated potassium currents are rather small. Thus, their role in burst interruption has to be revisited. An alternative role in high calcium level oscillations is proposed and an alternative burst interruption model is presented. It also turns out that sodium currents are more relevant than expected so far. Experiments are proposed to verify these predictions.

q-bio.CB

Mechanisms of organogenesis of primary lymphoid follicles

Primary lymphoid follicles in secondary lymphoid tissue of mammals are the backbone for the formation of follicular dendritic cell networks. These are important for germinal center reactions. In the context of organogenesis molecular requirements for the formation of follicles have been identified. The present study complements this work with a simulation of the dynamics of the primary lymphoid follicle formation. In contrast to other problems of pattern formation, here, the homeostasis of the cell population is not governed by a growth-death balance but by a flow equilibrium of migrating cells. The influx of cells into secondary lymphoid tissue was extensively studied while less information is available about the efflux of lymphocytes from secondary lymphoid tissues. This study formulates the minimal requirements for cell efflux that guarantee a flow equilibrium and, thus, a stable primary lymphoid follicle. The model predicts that in addition to already identified mechanisms a negative regulation of the generation of follicular dendritic cells is required. Furthermore, a comparison with data concerning the microanatomy of secondary lymphoid tissues yields the conclusion that dynamical changes during the formation of FDC networks of the lymphatic endothelium are necessary to understand the genesis and maintenance of follicles.

q-bio.TO

An analysis of B cell selection mechanisms in germinal centers

Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for the antigen. The mechanism underlying B cell selection has not yet been defined. By employing an agent-based model, we show that for physiologically reasonable parameter values affinity maturation can neither be driven by competition for binding sites nor antigen -- even in the presence of competing secreted antibodies. Within the tested mechanisms, only clonal competition for T cell help or a refractory time for the interaction of centrocytes with follicular dendritic cells are found to enable affinity maturation while generating the experimentally observed germinal center characteristics and tolerating large variations in the initial antigen density.

q-bio.CB

A theory of Plasma Membrane Calcium Pump stimulation and activity

The ATP-driven Plasma Membrane Calcium pump or Ca(2+)-ATPase (PMCA) is characterized by a high affinity to calcium and a low transport rate compared to other transmembrane calcium transport proteins. It plays a crucial role for calcium extrusion from cells. Calmodulin is an intracellular calcium buffering protein which is capable in its Ca(2+) liganded form of stimulating the PMCA by increasing both the affinity to calcium and the maximum calcium transport rate. We introduce a new model of this stimulation process and derive analytical expressions for experimental observables in order to determine the model parameters on the basis of specific experiments. We furthermore develop a model for the pumping activity. The pumping description resolves the seeming contradiction of the Ca(2+):ATP stoichiometry of 1:1 during a translocation step and the observation that the pump binds two calcium ions at the intracellular site. The combination of the calcium pumping and the stimulation model correctly describes PMCA function. We find that the processes of calmodulin-calcium complex attachment to the pump and of stimulation have to be separated. Other PMCA properties are discussed in the framework of the model. The presented model can serve as a tool for calcium dynamics simulations and provides the possibility to characterize different pump isoforms by different type-specific parameter sets.

physics.bio-ph

Multicellular Tumor Spheroid in an off-lattice Voronoi/Delaunay cell model

We study multicellular tumor spheroids by introducing a new three-dimensional agent-based Voronoi/Delaunay hybrid model. In this model, the cell shape varies from spherical in thin solution to convex polyhedral in dense tissues. The next neighbors of the cells are provided by a weighted Delaunay triangulation with in average linear computational complexity. The cellular interactions include direct elastic forces and cell-cell as well as cell-matrix adhesion. The spatiotemporal distribution of two nutrients -- oxygen and glucose -- is described by reaction-diffusion equations. Viable cells consume the nutrients, which are converted into biomass by increasing the cell size during G_1 phase. We test hypotheses on the functional dependence of the uptake rates and use the computer simulation to find suitable mechanisms for induction of necrosis. This is done by comparing the outcome with experimental growth curves, where the best fit leads to an unexpected ratio of oxygen and glucose uptake rates. The model relies on physical quantities and can easily be generalized towards tissues involving different cell types. In addition, it provides many features that can be directly compared with the experiment.

q-bio.TO

A quantitative model for presynaptic free calcium dynamics during different stimulation protocols

The presynaptic free calcium dynamics of neurons due to various stimulation protocols is investigated in a mathematical model. The model includes calcium influx through voltage-dependent calcium channels, calcium buffering by endogenous and exogenous buffers as well as calcium efflux through ATP-driven plasma membrane calcium pumps and sodium/calcium exchangers. We want to support a specific way of modeling which starts on the level of single proteins. Each protein is represented by characteristics that are determined by single protein experiments and that are considered to be widely independent of neuron types. This allows the applications of the model to different classes of neurons and experiments. The procedure is demonstrated for single boutons of pyramidal neurons of the rat neocortex. The corresponding fluorescence measurements of Koester & Sakmann (2000, J. Physiol., 529, 625) are quantitatively reproduced. The model enables us to reconstruct the free calcium dynamics in neurons as it would have been without fluorescence indicators starting from the fluorescence data. We discuss the different calcium responses and find that during high-frequency stimulation an accumulation of free calcium occurs above some threshold stimulation frequency. The threshold frequency depends on the amount of fluorescence indicator used in the experiment.

physics.bio-ph