multiMiAT: an optimal microbiome-based association test for multicategory phenotypes

Abstract Microbes can affect the metabolism and immunity of human body incessantly, and the dysbiosis of human microbiome drives not only the occurrence but also the progression of disease (i.e. multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, the existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g. disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test for multicategory phenotypes (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the success of our method. Furthermore, multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer as well as for diverse statuses of Clostridium difficile infections.