Computational methods for meta'omic characterization of the human microbiome

Abstract

Among many surprising insights, the genomic revolution has helped us to realize that we're never alone and, in fact, barely human. For most of our lives, we share our bodies with some ten times as many microbes as human cells; these are resident in our gut and on nearly every body surface, and they are responsible for a tremendous diversity of metabolic activity, immunomodulation, and intercellular signaling. High-throughput sequencing has only recently provided a tool that allows exploration of microbial function, microbe-microbe, and host-microbe interactions in these complex and highly diverse ecologies.

Computational methods for interpreting metagenomic sequencing typically rely on the catalog of thousands of available microbial reference genomes. I will describe two bioinformatic pipelines using such approaches, the first the PhlAn tools for Phylogenetic Analysis. These provide efficient algorithms for taxonomic profiling within communities - identifying which organisms are present - and for phylogenetic reconstruction and placement of new genomes. The second method, ShortBRED, optimizes a Short Better REad Database for functional profiling to quantify genes and pathways within a community. I will conclude with comments on recent work in microbial community systems biology and open questions in the human microbiome's role in disease.

Dr. Curtis Huttenhower is an Associate Professor in the Department of Biostatistics at the Harvard School of Public Health and an Associate Member at the Broad Institute. He received his Ph.D. from Princeton University in the lab of Dr. Olga Troyanskaya, where he also performed his postdoctoral research at the Lewis-Sigler Institute. His lab participated extensively in the NIH Human Microbiome Project and focuses on computational methods for functional analysis of microbial communities. This includes systems biology reconstructions typically integrating metagenomic and metatranscriptomic assays, the human microbiome in autoimmune disease such as IBD, and its potential as a diagnostic tool and point of therapeutic intervention.