High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED.

PLoS Comput Biol
Authors
Keywords
Abstract

Profiling microbial community function from metagenomic sequencing data remains a computationally challenging problem. Mapping millions of DNA reads from such samples to reference protein databases requires long run-times, and short read lengths can result in spurious hits to unrelated proteins (loss of specificity). We developed ShortBRED (Short, Better Representative Extract Dataset) to address these challenges, facilitating fast, accurate functional profiling of metagenomic samples. ShortBRED consists of two components: (i) a method that reduces reference proteins of interest to short, highly representative amino acid sequences ("markers") and (ii) a search step that maps reads to these markers to quantify the relative abundance of their associated proteins. After evaluating ShortBRED on synthetic data, we applied it to profile antibiotic resistance protein families in the gut microbiomes of individuals from the United States, China, Malawi, and Venezuela. Our results support antibiotic resistance as a core function in the human gut microbiome, with tetracycline-resistant ribosomal protection proteins and Class A beta-lactamases being the most widely distributed resistance mechanisms worldwide. ShortBRED markers are applicable to other homology-based search tasks, which we demonstrate here by identifying phylogenetic signatures of antibiotic resistance across more than 3,000 microbial isolate genomes. ShortBRED can be applied to profile a wide variety of protein families of interest; the software, source code, and documentation are available for download at http://huttenhower.sph.harvard.edu/shortbred.

Year of Publication
2015
Journal
PLoS Comput Biol
Volume
11
Issue
12
Pages
e1004557
Date Published
2015 Dec
ISSN
1553-7358
URL
DOI
10.1371/journal.pcbi.1004557
PubMed ID
26682918
PubMed Central ID
PMC4684307
Links
Grant list
DP2 DK098089 / DK / NIDDK NIH HHS / United States
R01 GM099538 / GM / NIGMS NIH HHS / United States
DP2DK098089 / DK / NIDDK NIH HHS / United States
R01GM099538 / GM / NIGMS NIH HHS / United States
R01 HG005969 / HG / NHGRI NIH HHS / United States
R01HG005969 / HG / NHGRI NIH HHS / United States