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

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ShortBRED is a new tool for fast and accurate metagenomic functional profiling. It identifies antibiotic resistance genes in the human gut microbiome, revealing widespread distribution of key resistance mechanisms globally.

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Area of Science:

  • Microbiology
  • Bioinformatics
  • Genomics

Background:

  • Metagenomic sequencing is crucial for understanding microbial communities.
  • Computational challenges exist in functional profiling, including long run-times and reduced specificity due to short DNA reads.
  • Accurate mapping of DNA reads to protein databases is essential for reliable functional analysis.

Purpose of the Study:

  • To develop a computationally efficient and accurate method for metagenomic functional profiling.
  • To introduce ShortBRED (Short, Better Representative Extract Dataset) for addressing the challenges of speed and specificity in metagenomic analysis.
  • To profile antibiotic resistance protein families in the human gut microbiome across diverse populations.

Main Methods:

  • ShortBRED utilizes a two-component approach: generating short, representative amino acid "markers" from reference proteins and searching metagenomic reads against these markers.
  • The method was evaluated using synthetic data.
  • Applied to profile antibiotic resistance genes in gut microbiomes from the United States, China, Malawi, and Venezuela.

Main Results:

  • ShortBRED enables fast and accurate functional profiling of metagenomic samples.
  • Antibiotic resistance is a core function of the human gut microbiome.
  • Tetracycline-resistant ribosomal protection proteins and Class A beta-lactamases are the most prevalent resistance mechanisms globally.
  • ShortBRED markers were successfully used to identify phylogenetic signatures of antibiotic resistance in over 3,000 microbial isolate genomes.

Conclusions:

  • ShortBRED effectively overcomes computational challenges in metagenomic functional profiling.
  • The human gut microbiome harbors a globally distributed repertoire of antibiotic resistance genes.
  • ShortBRED is a versatile tool applicable to profiling various protein families and for phylogenetic analysis.