Quantifying Taxonomic and Functional Diversity of Metagenomes from Next-Generation Sequencing Data

• Activity Number: 224
• Type: Topic Contributed
• Date/Time: Monday, July 30, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistical Computing
• Author(s): Katherine Pollard*+ and Thomas J. Sharpton and Rebecca Truty and Joshua Ladau and Samantha Riesenfeld and Guillaume Jospin and Steven Kembel and Morgan Langille and James O'Dwyer and Dongying Wu and Jessica Green and Jonathan Eisen
• Companies: Gladstone Institutes, UCSF and Gladstone Institutes, UCSF and Gladstone Institutes, UCSF and Gladstone Institutes, UCSF and Gladstone Institutes, UCSF and University of California at Davis and University of Oregon and University of California at Davis and Santa Fe Institute and University of California at Davis and University of Oregon and University of California at Davis
• Keywords: phylogenetics ; Markov models ; metagenomics ; next-generation sequencing ; bioinformatics ; diversity

Abstract

Analysis of shotgun sequenced environmental DNA, known as metagenomics, promises insight into the taxonomic and functional diversity of microbial communities. To overcome challenges associated with the fragmentary, non-overlapping nature of metagenomic sequence data, we developed novel statistical phylogenetic methods for identifying operational taxonomic units (OTUs) and operational protein families (OPFs), as well as read-based error detection methods and a simulation pipeline for testing the performance of these and other metagenomics analysis tools. A key feature of our approach is the use of full-length genes from sequenced microbial genomes to guide the placement of metagenomic sequences into phylogenetic trees and probabilistic model based alignments (e.g., via profile hidden Markov models or stochastic context free grammars). We generated a database of 340,000 OPFs that encapsulates significantly more protein functional diversity than existing databases (e.g., PFAM). Using niche modeling methods, we leveraged our database and analysis tools to predict and compare the distributions of OTUs and OPFs across the world's oceans, North American soils, and human gut communities.