Ornithine decarboxylase antizyme finder (OAF): fast and reliable detection of antizymes with frameshifts in mRNAs.
BACKGROUND
Ornithine decarboxylase antizymes are proteins which negatively regulate cellular polyamine levels via their affects on polyamine synthesis and cellular uptake. In virtually all organisms from yeast to mammals, antizymes are encoded by two partially overlapping open reading frames (ORFs). A +1 frameshift between frames is required for the synthesis of antizyme. Ribosomes change translation phase at the end of the first ORF in response to stimulatory signals embedded in mRNA. Since standard sequence analysis pipelines are currently unable to recognise sites of programmed ribosomal frameshifting, proper detection of full length antizyme coding sequences (CDS) requires conscientious manual evaluation by a human expert. The rapid growth of sequence information demands less laborious and more cost efficient solutions for this problem. This manuscript describes a rapid and accurate computer tool for antizyme CDS detection that requires minimal human involvement.


RESULTS
We have developed a computer tool, OAF (ODC antizyme finder) for identifying antizyme encoding sequences in spliced or intronless nucleic acid sequenes. OAF utilizes a combination of profile hidden Markov models (HMM) built separately for the products of each open reading frame constituting the entire antizyme coding sequence. Profile HMMs are based on a set of 218 manually assembled antizyme sequences. To distinguish between antizyme paralogs and orthologs from major phyla, antizyme sequences were clustered into twelve groups and specific combinations of profile HMMs were designed for each group. OAF has been tested on the current version of dbEST, where it identified over six thousand Expressed Sequence Tags (EST) sequences encoding antizyme proteins (over two thousand antizyme CDS in these ESTs are non redundant).


CONCLUSIONS
OAF performs well on raw EST sequences and mRNA sequences derived from genomic annotations. OAF will be used for the future updates of the RECODE database. OAF can also be useful for identifying novel antizyme sequences when run with relaxed parameters. It is anticipated that OAF will be used for EST and genome annotation purposes. OAF outputs sequence annotations in fasta, genbank flat file or XML format. The OAF web interface and the source code are freely available at http://recode.ucc.ie/oaf/ and at a mirror site http://recode.genetics.utah.edu/oaf/.
Bekaert
Michaël
M
School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland. mbekaert@gmail.com
Ivanov
Ivaylo P
IP
Atkins
John F
JF
Baranov
Pavel V
PV
D000465:Algorithms; D001483:Base Sequence; D004791:Enzyme Inhibitors; D018965:Frameshifting, Ribosomal / Q000235:genetics*; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000235:genetics*; D065108:Ornithine Decarboxylase Inhibitors; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase