Robustness and reproducibility of simple and complex synthetic logic circuit designs using a DBTL loop.

Computational tools addressing various components of design-build-test-learn (DBTL) loops for the construction of synthetic genetic networks exist but do not generally cover the entire DBTL loop. This manuscript introduces an end-to-end sequence of tools that together form a DBTL loop called Design Assemble Round Trip (DART). DART provides rational selection and refinement of genetic parts to construct and test a circuit. Computational support for experimental process, metadata management, standardized data collection and reproducible data analysis is provided via the previously published Round Trip (RT) test-learn loop. The primary focus of this work is on the Design Assemble (DA) part of the tool chain, which improves on previous techniques by screening up to thousands of network topologies for robust performance using a novel robustness score derived from dynamical behavior based on circuit topology only. In addition, novel experimental support software is introduced for the assembly of genetic circuits. A complete design-through-analysis sequence is presented using several OR and NOR circuit designs, with and without structural redundancy, that are implemented in budding yeast. The execution of DART tested the predictions of the design tools, specifically with regard to robust and reproducible performance under different experimental conditions. The data analysis depended on a novel application of machine learning techniques to segment bimodal flow cytometry distributions. Evidence is presented that, in some cases, a more complex build may impart more robustness and reproducibility across experimental conditions. Graphical Abstract.

Calibration of an Adaptive Genetic Algorithm for Modeling Opinion Diffusion.

Genetic algorithms mimic the process of natural selection in order to solve optimization problems with minimal assumptions and perform well when the objective function has local optima on the search space. These algorithms treat potential solutions to the optimization problem as chromosomes, consisting of genes which undergo biologically-inspired operators to identify a better solution. Hyperparameters or control parameters determine the way these operators are implemented. We created a genetic algorithm in order to fit a DeGroot opinion diffusion model using limited data, making use of selection, blending, crossover, mutation, and survival operators. We adapted the algorithm from a genetic algorithm for design of mixture experiments, but the new algorithm required substantial changes due to model assumptions and the large parameter space relative to the design space. In addition to introducing new hyperparameters, these changes mean the hyperparameter values suggested for the original algorithm cannot be expected to result in optimal performance. To make the algorithm for modeling opinion diffusion more accessible to researchers, we conduct a simulation study investigating hyperparameter values. We find the algorithm is robust to the values selected for most hyperparameters and provide suggestions for initial, if not default, values and recommendations for adjustments based on algorithm output.

Using a novel genetic algorithm to assess peer influence on willingness to use pre-exposure prophylaxis in networks of Black men who have sex with men.

The DeGroot model for opinion diffusion over social networks dates back to the 1970s and models the mechanism by which information or disinformation spreads through a network, changing the opinions of the agents. Extensive research exists about the behavior of the DeGroot model and its variations over theoretical social networks; however, research on how to estimate parameters of this model using data collected from an observed network diffusion process is much more limited. Existing algorithms require large data sets that are often infeasible to obtain in public health or social science applications. In order to expand the use of opinion diffusion models to these and other applications, we developed a novel genetic algorithm capable of recovering the parameters of a DeGroot opinion diffusion process using small data sets, including those with missing data and more model parameters than observed time steps. We demonstrate the efficacy of the algorithm on simulated data and data from a social network intervention leveraging peer influence to increase willingness to take pre-exposure prophylaxis in an effort to decrease transmission of human immunodeficiency virus among Black men who have sex with men.

Performance of a Genetic Algorithm for Estimating DeGroot Opinion Diffusion Model Parameters for Health Behavior Interventions.

Leveraging social influence is an increasingly common strategy to change population behavior or acceptance of public health policies and interventions; however, assessing the effectiveness of these social network interventions and projecting their performance at scale requires modeling of the opinion diffusion process. We previously developed a genetic algorithm to fit the DeGroot opinion diffusion model in settings with small social networks and limited follow-up of opinion change. Here, we present an assessment of the algorithm performance under the less-than-ideal conditions likely to arise in practical applications. We perform a simulation study to assess the performance of the algorithm in the presence of ordinal (rather than continuous) opinion measurements, network sampling, and model misspecification. We found that the method handles alternate models well, performance depends on the precision of the ordinal scale, and sampling the full network is not necessary to use this method. We also apply insights from the simulation study to investigate notable features of opinion diffusion models for a social network intervention to increase uptake of pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM).