Abstract
Alterations in human microbial communities are intricately linked to the onset and progression of diseases. Identifying the key microbes driving these community changes is crucial, as they may serve as valuable biomarkers for disease prevention, diagnosis, and treatment. However, there remains a need for further research to develop effective methods for addressing this critical task. This is primarily because defining the driver microbe requires consideration not only of each microbe's individual contributions but also their interactions. This paper introduces a novel framework, called mbDriver, for identifying driver microbes based on microbiome abundance data collected at discrete time points. mbDriver comprises three main components: (i) data preprocessing of time-series abundance data using smoothing splines based on the negative binomial distribution, (ii) parameter estimation for the generalized Lotka-Volterra (gLV) model using regularized least squares, and (iii) quantification of each microbe's contribution to the community's steady state by manipulating the causal graph implied by gLV equations. The performance of nonparametric spline-based denoising and regularized least squares estimation is comprehensively evaluated on simulated datasets, demonstrating superiority over existing methods. Furthermore, the practical applicability and effectiveness of mbDriver are showcased using a dietary fiber intervention dataset and an ulcerative colitis dataset. Notably, driver microbes identified in the dietary fiber intervention dataset exhibit significant effects on the abundances of short-chain fatty acids, while those identified in the ulcerative colitis dataset show a significant correlation with metabolism-related pathways.