High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED
By James Kaminski, Molly K. Gibson, Eric A. Franzosa, Nicola Segata, Gautam Dantas, Curtis Huttenhower. PLoS Comput. Biol., 2015
312 citations recorded by the source corpus.
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
Subfields: Molecular Biology, Molecular Medicine
View Paper: https://www.semanticscholar.org/paper/98cdd92447ec6c0af7c210261e49a1352b143921
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In Molecular Biology
- Michael Jeffrey Gandal
- Rosa Krajmalnik-Brown
- Elhanan Borenstein
- Michael J. Sweredoski
- Gautam Dantas
- Daniel H. Geschwind
- Janet K. Jansson
- Dae-Wook Kang
In Molecular Medicine
Citations in the corpus
- Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics (2016, background): “…by unrestricted sequencing of the genome of all microorganisms present in a sample (hereafter referred to as shotgun libraries); alternatively, inferences can be made by sequencing PCR amplicons from the ribosomal 16S RNA gene (hereafter referred to as 16S libraries), whose domain is…”
- Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019, background): “HUMAnN2 and ShortBRED analyses (Franzosa et al., 2018; Kaminski et al., 2015) of metagenomic data enabled exploring possible pathways for taurine and 5AV metabolism.”
- The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation (2016, background): “, the abundances and diversity of metabolic pathways or resistance genes), new computational tools can now analyze short reads from whole-metagenome shotgun sequencing, neatly sidestepping the challenges of read assembly from a complex and uncultured community [12–14].”