Use of simulation to optimize a sweet corn breeding program: implementing genomic selection and doubled haploid technology.

Genomic selection and doubled haploids hold significant potential to enhance genetic gains and shorten breeding cycles across various crops. Here, we utilized stochastic simulations to investigate the best strategies for optimize a sweet corn breeding program. We assessed the effects of incorporating varying proportions of old and new parents into the crossing block (3:1, 1:1, 1:3, and 0:1 ratio, representing different degrees of parental substitution), as well as the implementation of genomic selection in two distinct pipelines: one calibrated using the phenotypes of testcross parents (GSTC scenario) and another using F1 individuals (GSF1). Additionally, we examined scenarios with doubled haploids, both with (DH) and without (DHGS) genomic selection. Across 20 years of simulated breeding, we evaluated scenarios considering traits with varying heritabilities, the presence or absence of genotype-by-environment effects, and two program sizes (50 vs 200 crosses per generation). We also assessed parameters such as parental genetic mean, average genetic variance, hybrid mean, and implementation costs for each scenario. Results indicated that within a conventional selection program, a 1:3 parental substitution ratio (replacing 75% of parents each generation with new lines) yielded the highest performance. Furthermore, the GSTC model outperformed the GSF1 model in enhancing genetic gain. The DHGS model emerged as the most effective, reducing cycle time from 5 to 4 years and enhancing hybrid gains despite increased costs. In conclusion, our findings strongly advocate for the integration of genomic selection and doubled haploids into sweet corn breeding programs, offering accelerated genetic gains and efficiency improvements.

An agent-based simulation model to compare different reproductive strategies in cow-calf operations: Economic performance.

In a companion paper, Ojeda-Rojas et al. (2021) [1] describe a stochastic agent-based simulation (ABS) model of a cow-calf operation on a commercial farm in São Paulo, Brazil. The model's parameterization was based on data collected from two sources: a real beef cattle herd and related scientific literature. Based on the mentioned simulation model, this study aims to assess the economic outcome of 10 different reproductive scenarios: Natural mating only (ONM); one timed artificial insemination (TAI) plus natural mating (NM) (1TAI + NM); two TAI plus NM, with 24, 32, and 40 days between TAI (2TAI/24 + NM, 2TAI/32 + NM, and 2TAI/40 + NM, respectively); three TAI without NM, with 24, 32, and 40 days between TAI (3TAI/24, 3TAI/32, and 3TAI/40, respectively); and three TAI plus NM, with an interval between TAI of 24 (3TAI/24 + NM) and 32 days (3TAI/32 + NM). The simulation was performed on an animal-by-animal basis over a time horizon of 5000 days. Each scenario had 32 farms, and each farm kept up to 400 adult females. According to the scenario, a bull population was composed of 0, 7, or 15 individuals. The outcomes, represented as means ± standard deviations, were assessed after reaching a steady-state (1825 days). The model outcomes showed that the 3TAI/24 + NM scenario resulted in higher incomes (US$ 96,479.19 ± 709.81), whereas the ONM scenario had the lowest incomes (US$ 79,753.37 ± 741.87). The 3TAI/24 + NM (US$ 101.720.63 ± 79.21) and ONM (US$ 90.898.58 ± 59.17) scenarios presented the highest and lowest total operating costs (TOC), respectively. However, when TOC was evaluated per kg of the weaned calf, the highest and lowest costs were associated with the ONM (US$ 2.81 ± 0.03/kg) and 2TAI/24 + NM (US$ 2.17 ± 0,04/kg) scenarios, respectively. Our model suggests that reproductive strategies that use TAI have a better economic performance than those under NM. However, when performing three TAI with an interval of 40 days, the benefit was lower; in some cases, it was even worse than the ONM. Combining TAI with early pregnancy diagnosis resulted in better economic performance than other TAI programs and NM. The 2TAI/24 + NM scenario outperformed the others due to the contrast between its high income and moderate costs. Beef cattle production is a highly complex system. Simulations models, specifically ABS models, could make the decision-making process on complex systems straightforward and effective. Furthermore, ABS models can overcome the limitations of conventional research approaches, such as high costs and long experimentation periods.

An agent-based simulation model to compare different reproductive strategies in cow-calf operations: Technical performance.

The objective of this study was to create a stochastic, agent-based simulation model of a synthetic population of beef cattle, and then use it to compare the technical performance of different reproductive strategies. The model was parameterized using data from a real beef cattle herd and from the peer-reviewed scientific literature to represent a Nelore cattle herd in the state of São Paulo, Brazil. Ten scenarios were evaluated: natural mating (NM) only (ONM); one timed artificial insemination (TAI) plus NM (1TAI + NM); two TAI plus NM, with 24, 32, and 40 days between inseminations (2TAI/24 + NM, 2TAI/32 + NM, and 2TAI/40 + NM, respectively); three TAI without NM, with 24, 32, and 40 days between TAI (3TAI/24, 3TAI/32, and 3TAI/40, respectively); and three TAI plus NM, with 24 and 32 days (3TAI/24 + NM and 3TAI/32 + NM, respectively). NM began 10 days after the last TAI and was performed until the end of the breeding season. The size of the female herd was set to contain up to 400 individuals. The bull population was established at 0, 7, or 15 bulls depending on the used scenario. Simulation was performed for 5000 days. The outcomes for each scenario are means ± S.E. assessed on 32 farms at 1-day time intervals and on an animal-by-animal basis after steady state was reached (1825 days). The 3TAI/24 + NM scenario resulted in a greater number of births (279.85 ± 0.47 births), while the ONM scenario had the least value (202.38 ± 0.43 births). The heaviest males and females at weaning belonged to 3TAI/24, with 190.85 ± 0.17 kg for males and 173.89 ± 0.13 kg for females. The ONM scenario had the lightest males (166.84 ± 0.18 kg) and females (151.75 ± 0.16 kg). The greatest and least total pregnancy rates were found in 3TAI/24 + NM (0.91 ± 0.00) and ONM (0.62 ± 0.00), respectively. The ONM scenario required 52.5 days more than scenarios that included TAI to reach 50% of pregnancy. The greatest ages at culling for cows was 3TAI/24 + NM (3658.88 ± 10.41 days). In contrast, the lowest age at culling was found in ONM (2823.93 ± 8.28 days). We concluded that the proposed model represents the main interactions of a real beef cattle herd. It has all the advantages of a physical experiment, but does not require incurring significant expenses nor altering the real system. This study offers evidence that the scenarios that present the best technical performance are those that used TAI with a 24-day interval between inseminations.

Stochastic Modeling and Simulation of Viral Evolution.

RNA viruses comprise vast populations of closely related, but highly genetically diverse, entities known as quasispecies. Understanding the mechanisms by which this extreme diversity is generated and maintained is fundamental when approaching viral persistence and pathobiology in infected hosts. In this paper, we access quasispecies theory through a mathematical model based on the theory of multitype branching processes, to better understand the roles of mechanisms resulting in viral diversity, persistence and extinction. We accomplish this understanding by a combination of computational simulations and the theoretical analysis of the model. In order to perform the simulations, we have implemented the mathematical model into a computational platform capable of running simulations and presenting the results in a graphical format in real time. Among other things, we show that the establishment of virus populations may display four distinct regimes from its introduction into new hosts until achieving equilibrium or undergoing extinction. Also, we were able to simulate different fitness distributions representing distinct environments within a host which could either be favorable or hostile to the viral success. We addressed the most used mechanisms for explaining the extinction of RNA virus populations called lethal mutagenesis and mutational meltdown. We were able to demonstrate a correspondence between these two mechanisms implying the existence of a unifying principle leading to the extinction of RNA viruses.

Rule-Based Models and Applications in Biology.

Complex systems are governed by dynamic processes whose underlying causal rules are difficult to unravel. However, chemical reactions, molecular interactions, and many other complex systems can be usually represented as concentrations or quantities that vary over time, which provides a framework to study these dynamic relationships. An increasing number of tools use these quantifications to simulate dynamically complex systems to better understand their underlying processes. The application of such methods covers several research areas from biology and chemistry to ecology and even social sciences.In the following chapter, we introduce the concept of rule-based simulations based on the Stochastic Simulation Algorithm (SSA) as well as other mathematical methods such as Ordinary Differential Equations (ODE) models to describe agent-based systems. Besides, we describe the mathematical framework behind Kappa (κ), a rule-based language for the modeling of complex systems, and some extensions for spaßtial models implemented in PISKaS (Parallel Implementation of a Spatial Kappa Simulator). To facilitate the understanding of these methods, we include examples of how these models can be used to describe population dynamics in a simple predator-prey ecosystem or to simulate circadian rhythm changes.

Diffusion approximation-based simulation of stochastic ion channels: which method to use?

To study the effects of stochastic ion channel fluctuations on neural dynamics, several numerical implementation methods have been proposed. Gillespie's method for Markov Chains (MC) simulation is highly accurate, yet it becomes computationally intensive in the regime of a high number of channels. Many recent works aim to speed simulation time using the Langevin-based Diffusion Approximation (DA). Under this common theoretical approach, each implementation differs in how it handles various numerical difficulties-such as bounding of state variables to [0,1]. Here we review and test a set of the most recently published DA implementations (Goldwyn et al., 2011; Linaro et al., 2011; Dangerfield et al., 2012; Orio and Soudry, 2012; Schmandt and Galán, 2012; Güler, 2013; Huang et al., 2013a), comparing all of them in a set of numerical simulations that assess numerical accuracy and computational efficiency on three different models: (1) the original Hodgkin and Huxley model, (2) a model with faster sodium channels, and (3) a multi-compartmental model inspired in granular cells. We conclude that for a low number of channels (usually below 1000 per simulated compartment) one should use MC-which is the fastest and most accurate method. For a high number of channels, we recommend using the method by Orio and Soudry (2012), possibly combined with the method by Schmandt and Galán (2012) for increased speed and slightly reduced accuracy. Consequently, MC modeling may be the best method for detailed multicompartment neuron models-in which a model neuron with many thousands of channels is segmented into many compartments with a few hundred channels.

Modelagem de ocorrência e densidade de juvenis de Callinectes sapidus (Decapoda, Portunidae) em dois estuários do Rio Grande do Sul, com dados zero-inflacionados / Occurrence and density modeling of juvenile Callinectes sapidus (Decapoda, Portunidae) in two estuaries in Rio Grande do Sul state, with zero-inflated data

Zero-inflated counting data of juvenile blue crabs (Callinectes sapidus Rathbun, 1896) collected in two estuaries of Rio Grande do Sul are the object of the present study. These data led to the formulation of hierarchical models that quantify the effect of categorical covariates months and location on the probability of occurrence and density of these populations, taking imperfect detection into account. Nonhierarchical models were also developed for comparison. A Bayesian approach was adopted for estimating model parameters using the Markov Chain Monte Carlo (MCMC) simulation technique. Model comparison was performed according to the Deviance Information Criterion (DIC). Hierarchical models resulted in better fits than conventional ones, mitigated the problem of excess zeros and allowed for simultaneous analysis of the probability of occurrence and the density of juvenile blue crab. The probability of occurrence of Class 2 juveniles in the Lagoa dos Patos estuary increases at larger distance from the mouth while in Tramandaí the occurrence is more likely for intermediate distances. In both estuaries the occurrence is more likely in the summer and winter months. Regarding density of Class 2 juveniles, there is marked variation among the months of the year; and is overall higher in the Tramandaí estuary.(AU)

Dados de contagem de juvenis de siri-azul (Callinectes sapidus Rathbun, 1896) coletados em dois estuários do Rio Grande do Sul são objeto do presente estudo. Por se encontrarem zero-inflacionados, esses dados motivaram a formulação de modelos hierárquicos, que quantificam o efeito das covariáveis categóricas mês e local sobre a probabilidade de ocorrência e densidade dessas populações, levando em conta a detecção imperfeita. Foram também desenvolvidos modelos não-hierárquicos para comparação. Uma abordagem Bayesiana foi adotada para a estimação dos parâmetros dos modelos por simulação Monte Carlo com Cadeias de Markov (MCMC). A comparação entre modelos foi feita com o Critério de Informação da Deviância (DIC). Os modelos hierárquicos apresentaram ajustes melhores que os modelos convencionais, mitigaram o problema do excesso de zeros e permitiram analisar simultaneamente as probabilidades de ocorrência e a densidade de juvenis de siri-azul. No estuário da Lagoa dos Patos, a probabilidade de ocorrência de juvenis na Classe 2 aumenta com a distância da desembocadura, enquanto em Tramandaí os pontos intermediários apresentam as maiores probabilidades. Em ambos os estuários a ocorrência é mais provável nos meses de verão e de inverno. A densidade de juvenis da Classe 2 apresenta marcada variação em relação aos meses do ano sendo, em geral, maior no estuário de Tramandaí.(AU)

Modelagem de ocorrência e densidade de juvenis de Callinectes sapidus (Decapoda, Portunidae) em dois estuários do Rio Grande do Sul, com dados zero-inflacionados / Occurrence and density modeling of juvenile Callinectes sapidus (Decapoda, Portunidae) in two estuaries in Rio Grande do Sul state, with zero-inflated data

Zero-inflated counting data of juvenile blue crabs (Callinectes sapidus Rathbun, 1896) collected in two estuaries of Rio Grande do Sul are the object of the present study. These data led to the formulation of hierarchical models that quantify the effect of categorical covariates months and location on the probability of occurrence and density of these populations, taking imperfect detection into account. Nonhierarchical models were also developed for comparison. A Bayesian approach was adopted for estimating model parameters using the Markov Chain Monte Carlo (MCMC) simulation technique. Model comparison was performed according to the Deviance Information Criterion (DIC). Hierarchical models resulted in better fits than conventional ones, mitigated the problem of excess zeros and allowed for simultaneous analysis of the probability of occurrence and the density of juvenile blue crab. The probability of occurrence of Class 2 juveniles in the Lagoa dos Patos estuary increases at larger distance from the mouth while in Tramandaí the occurrence is more likely for intermediate distances. In both estuaries the occurrence is more likely in the summer and winter months. Regarding density of Class 2 juveniles, there is marked variation among the months of the year; and is overall higher in the Tramandaí estuary.

Dados de contagem de juvenis de siri-azul (Callinectes sapidus Rathbun, 1896) coletados em dois estuários do Rio Grande do Sul são objeto do presente estudo. Por se encontrarem zero-inflacionados, esses dados motivaram a formulação de modelos hierárquicos, que quantificam o efeito das covariáveis categóricas mês e local sobre a probabilidade de ocorrência e densidade dessas populações, levando em conta a detecção imperfeita. Foram também desenvolvidos modelos não-hierárquicos para comparação. Uma abordagem Bayesiana foi adotada para a estimação dos parâmetros dos modelos por simulação Monte Carlo com Cadeias de Markov (MCMC). A comparação entre modelos foi feita com o Critério de Informação da Deviância (DIC). Os modelos hierárquicos apresentaram ajustes melhores que os modelos convencionais, mitigaram o problema do excesso de zeros e permitiram analisar simultaneamente as probabilidades de ocorrência e a densidade de juvenis de siri-azul. No estuário da Lagoa dos Patos, a probabilidade de ocorrência de juvenis na Classe 2 aumenta com a distância da desembocadura, enquanto em Tramandaí os pontos intermediários apresentam as maiores probabilidades. Em ambos os estuários a ocorrência é mais provável nos meses de verão e de inverno. A densidade de juvenis da Classe 2 apresenta marcada variação em relação aos meses do ano sendo, em geral, maior no estuário de Tramandaí.