DyMMM-LEAPS: An ML-based framework for modulating evenness and stability in synthetic microbial communities

Abstract

There have been a growing number of computational strategies to aid in the design of synthetic microbial consortia. A framework to identify regions in parametric space to maximize two essential properties, evenness and stability, is critical. In this study, we introduce DyMMM-LEAPS (Dynamic Multi-species Metabolic Modeling - Locating Evenness And stability in large Parametric Space), an extension of the DyMMM framework. Our method explores the large parametric space of genetic circuits in synthetic microbial communities to identify regions of evenness and stability. Due to the high computational costs of exhaustive sampling, we utilize adaptive sampling and surrogate modeling to reduce the number of simulations required to map the vast space. Our framework predicts engineering targets and computes their operating ranges to maximize the probability of the engineered community to have high evenness and stability. We demonstrate our approach by simulating five co-cultures and one three-strain culture with different social interactions (cooperation, competition, and predation) employing quorum-sensing based genetic circuits. In addition to guiding circuit tuning, our pipeline gives an opportunity for a detailed analysis of pockets of evenness and stability for the circuit under investigation, which can further help dissect the relationship between the two properties. DyMMM-LEAPS is easily customizable and can be expanded to a larger community with more complex interactions.