Single-Pass Classification of all Non-Coding Sequences in a Bacterial Genome Using Phylogenetic Profiles

Abstract

Identification and characterization of functional elements in the non-coding regions of genomes is an elusive and time consuming activity whose output does not keep up with the pace of genome sequencing. Hundreds of bacterial genomes lay unexploited in terms of non-coding sequence analysis although they may conceal a wide diversity of novel RNA genes, riboswitches or other regulatory elements. We describe a strategy that exploits the entirety of available bacterial genomes to classify all non-coding elements of a selected reference species in a single pass. This method clusters non-coding elements based on their profile of presence among species. Most non-coding RNAs display specific signatures that enable their grouping in distinct clusters, away from sequence conservation noise and other elements such as promoters. We submitted 24 ncRNA candidates from Staphylococcus aureus to experimental validation and confirmed the presence of seven novel small RNAs or riboswitches. Besides offering a powerful method for de novo ncRNA identification, the analysis of phylogenetic profiles opens a new path towards the identification of functional relationships between co-evolving coding and non-coding elements.

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Footnotes

    • Received December 2, 2008.
    • Accepted February 9, 2009.
  • This manuscript is Open Access.

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