Systems Metagenomics: Applying Systems Biology Thinking to Human Microbiome Analysis

Abstract

Metagenomics is the science of analysing the structure and function of DNA samples taken from the environment (e.g. soil or human gut) as opposed to a single organism. So far, researchers have used traditional genomics tools and pipelines applied to metagenomics analysis such as species identification, sequence alignment and assembly. In addition to being computationally expensive, these approaches lack an emphasis on the functional profile of the sample regardless of species diversity, and how it changes under different conditions. It also ignores unculturable species and genes undergoing horizontal transfer. We propose a new pipeline based on taking a “systems” approach to metagenomics analysis, in this case to analyse human gut microbiome data. Instead of identifying existing species, we examine a sample as a self-contained, open system with a distinct functional profile. The pipeline was used to analyse data from an experiment performed on the gut microbiomes of lean, obese and overweight twins. Previous analysis of this data only focused on taxonomic binning. Using our systems metagenomics approach, our analysis found two very different functional profiles for lean and obese twins, with obese ones being distinctly more diverse. There are also interesting differences in metabolic pathways which could indicate specific driving forces for obesity.