Protein structure and function in healthy and disease genomes and microbiomes

Abstract

Biological molecular machinery is a complex system of many interactions, both within and outside a single cell. The DNA blueprint of this system, which is currently being compiled with increasingly high-throughput techniques, holds many of the answers. We aim to decipher this blueprint to understand how biological functionality is encoded in genomic data, whether by a variant, a gene, a genome, or a metagenome. Very generally, in application to human disease, this implies correlating the human genome or human-host microbiome function changes to disease- affected or healthy phenotypes. For disease-affected individuals, understanding the functional disruptions can highlight pathogenesis pathways and treatment routes. We’ve created computational methods for identifying the functional effects of both human genome and microbiome variation from genome and metagenome data, respectively. Notably, our microbiome analysis tools can be used in ecological as well as in human studies, while our analysis of the human genome variants has given broad insight into protein function. While our tools can not yet be used diagnostically, they are able to clearly identify molecular functions relevant to pathogenesis and requiring further follow up.