Delineating Virulent and Avirulent Taxa with Genomics and Metagenomics

Culture-independent analysis (aka matagenomics) has recently revealed tremendous diversity in the microbial communities inhabiting the human body and revolutionized our understanding of these communities primarily because the majority of microbial species cannot be cultured in the laboratory and thus, they remain poorly understood. The ability to characterize in detail the microbial constituents in human clinical specimens without culture may prove invaluable in public health as all surveillance and outbreak detection methods to date rely on culture, frequently failing to identify the key causative agent of a disease. In this talk, I will summarize our recently developed bioinformatics algorithms and approaches to deal with several challenges associated with metagenome-based analysis of clinical samples such as how to detect and quantify target species (e.g., pathogens) and genes (e.g., toxins) in complex, short-read metagenomes, and how to identify and genotype organisms with no previously sequenced representatives. Application of these tools to samples from foodborne diarrheal outbreaks showed that in many cases - but not all - the disease and healthy states of the gut microbial community can be distinguished from each other, opening new possibilities for diagnostics. I will also present our approaches to delineate between highly virulent and a-virulent populations recovered in metagenomes form these samples, as well as examples from Clostridium botulinum and Bacillus anthracis on how to distinguish pathogenic strains from their innocuous close relatives based on comparative analysis of the genomes of isolates. The tools are available for online analysis or download for standalone application through http://enve-omics.gatech.edu/