Detecting overlapping coding sequences in virus genomes.
BACKGROUND
Detecting new coding sequences (CDSs) in viral genomes can be difficult for several reasons. The typically compact genomes often contain a number of overlapping coding and non-coding functional elements, which can result in unusual patterns of codon usage; conservation between related sequences can be difficult to interpret--especially within overlapping genes; and viruses often employ non-canonical translational mechanisms--e.g. frameshifting, stop codon read-through, leaky-scanning and internal ribosome entry sites--which can conceal potentially coding open reading frames (ORFs).


RESULTS
In a previous paper we introduced a new statistic--MLOGD (Maximum Likelihood Overlapping Gene Detector)--for detecting and analysing overlapping CDSs. Here we present (a) an improved MLOGD statistic, (b) a greatly extended suite of software using MLOGD, (c) a database of results for 640 virus sequence alignments, and (d) a web-interface to the software and database. Tests show that, from an alignment with just 20 mutations, MLOGD can discriminate non-overlapping CDSs from non-coding ORFs with a typical accuracy of up to 98%, and can detect CDSs overlapping known CDSs with a typical accuracy of 90%. In addition, the software produces a variety of statistics and graphics, useful for analysing an input multiple sequence alignment.


CONCLUSIONS
MLOGD is an easy-to-use tool for virus genome annotation, detecting new CDSs--in particular overlapping or short CDSs--and for analysing overlapping CDSs following frameshift sites. The software, web-server, database and supplementary material are available at http://guinevere.otago.ac.nz/mlogd.html.
Firth
Andrew E
AE
Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand. aef@sanger.otago.ac.nz
Brown
Chris M
CM
D000465:Algorithms; D001665:Binding Sites; D003062:Codon; D018388:Codon, Terminator; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D019992:Databases as Topic; D016368:Frameshift Mutation; D005807:Genes, Overlapping; D005814:Genes, Viral; D016678:Genome; D016679:Genome, Viral; D016013:Likelihood Functions; D015233:Models, Statistical; D009154:Mutation; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012984:Software; D014780:Viruses
D003062:Codon; D018388:Codon, Terminator