A unified web cloud computing platform MiMedSurv for microbiome causal mediation analysis with survival responses

Abstract

Abstract In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server ( http://mimedsurv.micloud.kr ).

Keywords

• Causal mediation analysis
• Survival analysis
• Web cloud computing
• Causal inference
• Human microbiome