NORMALIZATION AND DIFFERENTIAL ABUNDANCE ANALYSIS OF METAGENOMIC BIOMARKER-GENE SURVEYS

High-throughput technologies such as whole targeted sequencing of marker-genes and whole metagenomic shotgun (WMS) sequencing have provided unprecedented insight into microbial communities and the interactions between their members. Statistical inference is a challenging task in analyzing these communities while accounting for a far too common limitation of metagenomic datasets: under-sampling. In this dissertation I present novel and robust methods for normalization and differential abundance testing of marker-gene surveys and whole metagenomic shotgun sequencing experiments. Using these methods I analyze one particular microbial community of interest, gut microbiota associated with diarrhea. One central problem in almost any metagenomic analysis is under-sampling of the microbial community. The analysis and interpretation of both marker-gene surveys and WMS sequencing data can bias mean and…