Quantitative Biology

Metastasis, the spread of cancer cells from a primary tumor to secondary location(s) in the human organism, is the ultimate cause of death for the majority of cancer patients. That is why, it is crucial to understand metastases evolution in order to successfully combat the disease. We consider a metastasized cancer cell population after medical treatment (e.g. chemotherapy). Arriving in a different environment the cancer cells may change their lifespan and reproduction, thus they may proliferate into different types. If the treatment is effective, in the context of branching processes it means, the reproduction of cancer cells is such that the mean offspring of each cell is less than one. However, it is possible mutations to occur during cell division cycle. These mutations can produce a new cancer cell type, which is resistant to the treatment. Cancer cells from this new type may lead to the rise of a non-extinction branching process. The above scenario leads us to the choice of a reducible multi-type age-dependent branching process as a relevant framework for studying the asymptotic behavior of such complex structures. Our previous theoretical results are related to the asymptotic behavior of the waiting time until the first occurrence of a mutant starting a non-extinction process and the modified hazard function as a measure of immediate recurrence of cancer disease. In the present paper these asymptotic results are used for developing numerical schemes and algorithms implemented in Python via the NumPy package for approximate calculation of the corresponding quantities. In conclusion, our conjecture is that this methodology can be advantageous in revealing the role of the lifespan distribution of the cancer cells in the context of cancer disease evolution and other complex cell population systems, in general.

The interpretation of sampling data plays a crucial role in policy response to the spread of a disease during an epidemic, such as the COVID-19 epidemic of 2020. However, this is a non-trivial endeavor due to the complexity of real world conditions and limits to the availability of diagnostic tests, which necessitate a bias in testing favoring symptomatic individuals. A thorough understanding of sampling confidence and bias is necessary in order make accurate conclusions. In this manuscript, we provide a stochastic model of sampling for assessing confidence in disease metrics such as trend detection, peak detection, and disease spread estimation. Our model simulates testing for a disease in an epidemic with known dynamics, allowing us to use Monte-Carlo sampling to assess metric confidence. This model can provide realistic simulated data which can be used in the design and calibration of data analysis and prediction methods. As an example, we use this method to show that trends in the disease may be identified using under 10000 biased samples each day, and an estimate of disease spread can be made with additional 1000-2000 unbiased samples each day. We also demonstrate that the model can be used to assess more advanced metrics by finding the precision and recall of a strategy for finding peaks in the dynamics.

A central question of evolutionary dynamics on graphs is whether or not a mutation introduced in a population of residents survives and eventually even spreads to the whole population, or gets extinct. The outcome naturally depends on the fitness of the mutant and the rules by which mutants and residents may propagate on the network, but arguably the most determining factor is the network structure. Some structured networks are transient amplifiers. They increase for a certain fitness range the fixation probability of beneficial mutations as compared to a well-mixed population. We study a perturbation methods for identifying transient amplifiers for death-Birth updating. The method includes calculating the coalescence times of random walks on graphs and finding the vertex with the largest remeeting time. If the graph is perturbed by removing an edge from this vertex, there is a certain likelihood that the resulting perturbed graph is a transient amplifier. We test all pairwise nonisomorphic cubic and quartic regular graphs up to a certain size and thus cover the whole structural range expressible by these graphs. We carry out a spectral analysis and show that the graphs from which the transient amplifiers can be constructed share certain structural properties. The graphs are path-like, have low conductance and are rather easy to divide into subgraphs by removing edges and/or vertices. This is connected with the subgraphs being identical (or almost identical) building blocks and the frequent occurrence of cut and/or hinge vertices. Identifying spectral and structural properties may promote finding and designing such networks.

In comparison with individual testing, group testing (also known as pooled testing) is more efficient in reducing the number of tests and potentially leading to tremendous cost reduction. As indicated in the recent article posted on the US FDA website, the group testing approach for COVID-19 has received a lot of interest lately. There are two key elements in a group testing technique: (i) the pooling matrix that directs samples to be pooled into groups, and (ii) the decoding algorithm that uses the group test results to reconstruct the status of each sample. In this paper, we propose a new family of pooling matrices from packing the pencil of lines (PPoL) in a finite projective plane. We compare their performance with various pooling matrices proposed in the literature, including 2D-pooling, P-BEST, and Tapestry, using the two-stage definite defectives (DD) decoding algorithm. By conducting extensive simulations for a range of prevalence rates up to 5%, our numerical results show that there is no pooling matrix with the lowest relative cost in the whole range of the prevalence rates. To optimize the performance, one should choose the right pooling matrix, depending on the prevalence rate. The family of PPoL matrices can dynamically adjust their column weights according to the prevalence rates and could be a better alternative than using a fixed pooling matrix.

Contact tracing is an effective method to control emerging diseases. Since the 1980's, mathematical modelers are developing a consistent theory for contact tracing, with the aim to find effective and efficient implementations of contact tracing, and to assess the effects of contact tracing on the spread of an infectious disease. Despite the progress made in the area, there remain important open questions. In addition, technological developments, especially in the field of molecular biology (genetic sequencing of pathogens) and modern communication (digital contact tracing), have posed new challenges for the modeling community. In the present paper, we discuss modeling approaches for contact tracing and identify some of the current challenges for the field.

The COVID-19 pandemic has resulted in more than 14.5 million infections and 6,04,917 deaths in 212 countries over the last few months. Different drug intervention acting at multiple stages of pathogenesis of COVID-19 can substantially reduce the infection induced,thereby decreasing the mortality. Also population level control strategies can reduce the spread of the COVID-19 substantially. Motivated by these observations, in this work we propose and study a multi scale model linking both within-host and between-host dynamics of COVID-19. Initially the natural history dealing with the disease dynamics is studied. Later, comparative effectiveness is performed to understand the efficacy of both the within-host and population level interventions. Findings of this study suggest that a combined strategy involving treatment with drugs such as Arbidol, remdesivir, Lopinavir/Ritonavir that inhibits viral replication and immunotherapies like monoclonal antibodies, along with environmental hygiene and generalized social distancing proved to be the best and optimal in reducing the basic reproduction number and environmental spread of the virus at the population level.

The World Health Organization (WHO) made the assessment that COVID-19 can be characterized as a pandemic on March 11, 2020. To the COVID-19 outbreak, there is no vaccination and no treatment. The only way to control the COVID-19 outbreak is sustained physical distancing. In this work, a simple control law was proposed to keep the infected individuals during the COVID-19 outbreak below the desired number. The proposed control law keeps the value of infected individuals controlled only adjusting the social distancing level. The stability analysis of the proposed control law is done and the uncertainties in the parameters were considered. A version of the proposed controller to daily update was developed. This is a very simple approach to the developed control law and can be calculated in a spreadsheet. In the end, numerical simulations were done to show the behavior of the number of infected individuals during an epidemic disease when the proposed control law is used to adjust the social distancing level.

Cancer cells obtain mutations which rely on the production of diffusible growth factors to confer a fitness benefit. These mutations can be considered cooperative, and studied as public goods games within the framework of evolutionary game theory. The population structure, benefit function and update rule all influence the evolutionary success of cooperators. We model the evolution of cooperation in epithelial cells using the Voronoi tessellation model. Unlike traditional evolutionary graph theory, this allows us to implement global updating, for which birth and death events are spatially decoupled. We compare, for a sigmoid benefit function, the conditions for cooperation to be favoured and/or beneficial for well mixed and structured populations. We find that when population structure is combined with global updating, cooperation is more successful than if there were local updating or the population were well-mixed. Interestingly, the qualitative behaviour for the well-mixed population and the Voronoi tessellation model is remarkably similar, but the latter case requires significantly lower incentives to ensure cooperation.

Synchronization, cooperation, and chaos are ubiquitous phenomena in nature. In a population composed of many distinct groups of individuals playing the prisoner's dilemma game, there exists a migration dilemma: No cooperator would migrate to a group playing the prisoner's dilemma game lest it should be exploited by a defector; but unless the migration takes place, there is no chance of the entire population's cooperator-fraction to increase. Employing a randomly rewired coupled map lattice of chaotic replicator maps, modelling replication-selection evolutionary game dynamics, we demonstrate that the cooperators -- evolving in synchrony -- overcome the migration dilemma to proliferate across the population when altruism is mildly incentivized making few of the demes play the leader game.

This study analyzed the morbidity and mortality rates of the COVID-19 pandemic in different prefectures of Japan. Under the constraint that daily maximum confirmed deaths and daily maximum cases should exceed 4 and 10, respectively, 14 prefectures were included, and cofactors affecting the morbidity and mortality rates were evaluated. In particular, the number of confirmed deaths was assessed excluding the cases of nosocomial infections and nursing home patients. A mild correlation was observed between morbidity rate and population density (R2=0.394). In addition, the percentage of the elderly per population was also found to be non-negligible. Among weather parameters, the maximum temperature and absolute humidity averaged over the duration were found to be in modest correlation with the morbidity and mortality rates, excluding the cases of nosocomial infections. The lower morbidity and mortality are observed for higher temperature and absolute humidity. Multivariate analysis considering these factors showed that determination coefficients for the spread, decay, and combined stages were 0.708, 0.785, and 0.615, respectively. These findings could be useful for intervention planning during future pandemics, including a potential second COVID-19 outbreak.