A multivariate zero-inflated logistic model for microbiome relative abundance data

The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive number of zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We propose a multivariate two-part model, zero-inflated logistic normal (ZILN) model to analyze the association of disease risk factors with individual microbial taxa and overall microbial community composition. This approach can naturally handle excessive numbers of zeros and the compositional data structure with the zero part and the logistic-normal part of the model. For parameter estimation, an estimating equations approach is employed and enables us to address the complex inter-taxa correlation structure induced by the hierarchical phylogenetic tree structure and the compositional data structure. This model is able to incorporate standard regularization approaches to deal with high dimensionality. Simulation shows that our model outperforms existing methods. Performance of our approach is also demonstrated through the application of the model in a real data set.