MarZIC: A Marginal mediation model for Zero-Inflated Compositional mediators with applications to microbiome data

TL;DR

This paper introduces MarZIC, a novel marginal mediation model designed for zero-inflated compositional mediators like microbiome data, effectively addressing zero-inflation and false zeros in causal pathway analysis.

Contribution

The paper presents a new marginal mediation analysis method that accounts for zero-inflation and compositional structure in microbiome data, filling a gap in existing causal inference techniques.

Findings

Outperforms existing methods in simulation studies

Effectively disentangles zero-inflation effects

Successfully applied to real microbiome data

Abstract

The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the excessive number of zero-valued sequencing reads in the data that is compounded by its compositional structure. The two main challenges raised by the zero-inflated data structure are: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are actually not zero (i.e., false zeros). We develop a novel marginal mediation analysis method under the potential-outcomes framework to fill this gap and show the marginal model can also account for the compositional structure. The mediation effect can be decomposed into two components that are inherent to the two-part nature of zero-inflated distributions. With probabilistic models to account for observing zeros, we also address the challenge with false zeros. A comprehensive simulation study and the application in a real microbiome study showcase our approach in comparison with existing approaches.