Proteogenomics for the enhanced discovery of bacterial biomarkers

As nucleic acid sequencing technologies become faster and less expensive, whole genome sequences are increasingly available. Advances in sequencing have enhanced our ability to detect potential bacterial bioterrorism agents and to predict biomarkers for yet uncharacterized or man-made pathogens. However, speed and ease of access are no substitute for accuracy. Indeed, errors in both structural and functional annotations of genomes are still frequent. Proteogenomics, in which proteomic data complements genomic sequencing to correct errors and improve gene annotation, has already been performed on several bacteria on the Centers for Disease Control and Prevention list of bioterrorism agents, revealing non-negligible errors that could hinder the detection of known strains and be propagated in emerging strains whose sequencing and annotation depend on similarities with known sequences. In this chapter, we review the fundamentals of proteogenomics, its application in the prevention of bioterrorism and protection of public health, specifi c techniques for future development, and the confi dence that should be afforded to resulting sequences.