title: Thousands of missed genes found in bacterial genomes and their analysis with COMBREX.
abstract: BACKGROUND
  The dramatic reduction in the cost of sequencing has allowed many researchers to join in the effort of sequencing and annotating prokaryotic genomes. Annotation methods vary considerably and may fail to identify some genes. Here we draw attention to a large number of likely genes missing from annotations using common tools such as Glimmer and BLAST.
  
  
  RESULTS
  By analyzing 1,474 prokaryotic genome annotations in GenBank, we identify 13,602 likely missed genes that are homologs to non-hypothetical proteins, and 11,792 likely missed genes that are homologs only to hypothetical proteins, yet have supporting evidence of their protein-coding nature from COMBREX, a newly created gene function database. We also estimate the likelihood that each potential missing gene found is a genuine protein-coding gene using COMBREX.
  
  
  CONCLUSIONS
  Our analysis of the causes of missed genes suggests that larger annotation centers tend to produce annotations with fewer missed genes than smaller centers, and many of the missed genes are short genes <300 bp. Over 1,000 of the likely missed genes could be associated with phenotype information available in COMBREX. 359 of these genes, found in pathogenic organisms, may be potential targets for pharmaceutical research. The newly identified genes are available on COMBREX's website.
  
  
  METHODS
  This article was reviewed by Daniel Haft, Arcady Mushegian, and M. Pilar Francino (nominated by David Ardell).
authors.affiliation: Department of Computer Science, University of Maryland, College Park, MD 20742, USA. dwood@cs.umd.edu
authors.forename: Derrick E
authors.initials: DE
authors.lastname: Wood
authors.forename: Henry
authors.initials: H
authors.lastname: Lin
authors.forename: Ami
authors.initials: A
authors.lastname: Levy-Moonshine
authors.forename: Rajiswari
authors.initials: R
authors.lastname: Swaminathan
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Chang
authors.forename: Brian P
authors.initials: BP
authors.lastname: Anton
authors.forename: Lais
authors.initials: L
authors.lastname: Osmani
authors.forename: Martin
authors.initials: M
authors.lastname: Steffen
authors.forename: Simon
authors.initials: S
authors.lastname: Kasif
authors.forename: Steven L
authors.initials: SL
authors.lastname: Salzberg
mesh_terms: D001419:Bacteria / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D005798:Genes, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D058977:Molecular Sequence Annotation / Q000379:methods*; D016366:Open Reading Frames; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D012984:Software