Identification of microbiota dynamics using robust parameter estimation methods.

The compositions of in-host microbial communities (microbiota) play a significant role in host health, and a better understanding of the microbiota's role in a host's transition from health to disease or vice versa could lead to novel medical treatments. One of the first steps toward this understanding is modeling interaction dynamics of the microbiota, which can be exceedingly challenging given the complexity of the dynamics and difficulties in collecting sufficient data. Methods such as principal differential analysis, dynamic flux estimation, and others have been developed to overcome these challenges. Despite their advantages, these methods are still vastly underutilized in fields such as mathematical biology, and one potential reason for this is their sophisticated implementation. While this paper focuses on applying principal differential analysis to microbiota data, we also provide comprehensive details regarding the derivation and numerics of this method and include a functional implementation for readers' benefit. For further validation of these methods, we demonstrate the feasibility of principal differential analysis using simulation studies and then apply the method to intestinal and vaginal microbiota data. In working with these data, we capture experimentally confirmed dynamics while also revealing potential new insights into the system dynamics.