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Ornithine decarboxylase antizyme finder (OAF): fast and reliable detection of antizymes with frameshifts in mRNAs.

Bekaert M, Ivanov IP, Atkins JF, Baranov PV - BMC Bioinformatics (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland. mbekaert@gmail.com

ABSTRACT

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).

Conclusion: 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/.

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OAZ clustering. A circular tree of OAZ sequences representing clustering that has been used to design profile-HMMs used by OAF.
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Figure 3: OAZ clustering. A circular tree of OAZ sequences representing clustering that has been used to design profile-HMMs used by OAF.

Mentions: To design profile HMMs exploited by OAF, we used a collection of protein sequences derived from mRNA fragments using manually assembled ESTs. These sequences were described in some detail in a recent antizyme review [10] and are available in this article as an Additional File 1 (manualOAZs.fasta). Evolutionary distances between protein sequences were estimated using a Neighbour-Joining algorithm and poisson correction evolutionary model implemented in MEGA3.1 program [37]. Based on these distances, sequences were clustered into 12 homologous groups for which separate pairs of profile HMMs were designed using HMMER [38]. These HMMs are used to allow discrimination among different antizyme paralogs and to permit approximate estimation of the taxonomic origins of antizyme encoding sequences. The clustering is shown on the tree generated with MEGA3.1 (see Figure 3).


Ornithine decarboxylase antizyme finder (OAF): fast and reliable detection of antizymes with frameshifts in mRNAs.

Bekaert M, Ivanov IP, Atkins JF, Baranov PV - BMC Bioinformatics (2008)

OAZ clustering. A circular tree of OAZ sequences representing clustering that has been used to design profile-HMMs used by OAF.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2375905&req=5

Figure 3: OAZ clustering. A circular tree of OAZ sequences representing clustering that has been used to design profile-HMMs used by OAF.
Mentions: To design profile HMMs exploited by OAF, we used a collection of protein sequences derived from mRNA fragments using manually assembled ESTs. These sequences were described in some detail in a recent antizyme review [10] and are available in this article as an Additional File 1 (manualOAZs.fasta). Evolutionary distances between protein sequences were estimated using a Neighbour-Joining algorithm and poisson correction evolutionary model implemented in MEGA3.1 program [37]. Based on these distances, sequences were clustered into 12 homologous groups for which separate pairs of profile HMMs were designed using HMMER [38]. These HMMs are used to allow discrimination among different antizyme paralogs and to permit approximate estimation of the taxonomic origins of antizyme encoding sequences. The clustering is shown on the tree generated with MEGA3.1 (see Figure 3).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland. mbekaert@gmail.com

ABSTRACT

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).

Conclusion: 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/.

Show MeSH
Related in: MedlinePlus