A highly adaptive microbiome-based association test for survival traits

作者：Koh Hyunwook; Livanos Alexandra E; Blaser Martin J; Li Huilin^*

来源：BMC Genomics, 2018, 19(1): 210.

DOI：10.1186/s12864-018-4599-8

• Microbiome-based survival analysis
• Microbiome-based association test
• Community-level association test
• Microbial group analysis
• High-dimensional compositional data analysis
• Phylogenetic tree

Background: There has been increasing interest in discovering microbial taxa that are associated with human health or disease, gathering momentum through the advances in next-generation sequencing technologies. Investigators have also increasingly employed prospective study designs to survey survival (i.e., time-to-event) outcomes, but current item-by-item statistical methods have limitations due to the unknown true association pattern. Here, we propose a new adaptive microbiome-based association test for survival outcomes, namely, optimal microbiome-based survival analysis (OMiSA). OMiSA approximates to the most powerful association test in two domains: 1) microbiome-based survival analysis using linear and non-linear bases of OTUs (MiSALN) which weighs rare, mid-abundant, and abundant OTUs, respectively, and 2) microbiome regression-based kernel association test for survival traits (MiRKAT-S) which incorporates different distance metrics (e.g., unique fraction (UniFrac) distance and Bray-Curtis dissimilarity), respectively.
Results: We illustrate that OMiSA powerfully discovers microbial taxa whether their underlying associated lineages are rare or abundant and phylogenetically related or not. OMiSA is a semi-parametric method based on a variance-component score test and a re-sampling method; hence, it is free from any distributional assumption on the effect of microbial composition and advantageous to robustly control type I error rates. Our extensive simulations demonstrate the highly robust performance of OMiSA. We also present the use of OMiSA with real data applications.
Conclusions: OMiSA is attractive in practice as the true association pattern is unpredictable in advance and, for survival outcomes, no adaptive microbiome-based association test is currently available.

• 出版日期2018-3-20