Hi Franck,
see below...

On Thu, 2014-04-24 at 18:30 +1000, fceru...@toulouse.inra.fr wrote:
> Hello,
> 
> I'm student in bioinformatics and I'm currently undergoing training at
> INRA Toulouse (France) under the supervision of Helene Chiapello and
> Christine Gaspin.
> 
> I have a question about the Mauve software concerning the "extract
> ortholog" feature provided by the GUI. Indeed, I have encountered
> several problems while analyzing a large dataset of 27 E. coli
> genomes: for several ortholog groups, I identified multiple
> overlapping coding sequences in the same genome.
> 
> After manual inspection, I realize that these overlapping CDS seem
> mainly enlight two situations :
> 
> => Annotation mistakes in the original genbank file: overlaping coding
> sequences are located at different reading frames in the same genomic
> region. In this case, I was able to choose one of the two coding
> sequences by looking at %identity and coverage of the alignments.
> 
> => Real overlapping coding sequences: strongly annotated and predicted
> CDS, located at same reading frame (with a coding sequence included in
> another one for example). It should also be possible here to choose
> the real otholog CDS among the two coding sequences by looking at
> alignment coverage.I'd like to know if a fix already exists to handle
> these cases. Or may be you plan to do it ? 

There is a bit of a nomenclature problem here. The software produces
something that should probably called a positional homolog group rather
than an ortholog group. Inference of orthology requires resolution of
phylogenetic relationships, and that is not happening within Mauve.
Instead, a relatively simple set of criteria are applied to identify
clusters of positionally homologous features: if a pair of features
overlap by at least a fixed percent (>50%) and have at least a
particular percent sequence identity over their length, they are called
as homologous. Those thresholds are adjustable via the graphical
interface.

With that said, in the situation you describe, both overlapping CDS
should be positional homologs to the aligned region in the other genome.
It sounds like you are more interested in the notion of functional
equivalence. The term ortholog was unfortunately bastardized by early
genomics researchers in this context to refer to functionally equivalent
homologous genes. You might be able to do some relatively simple
postprocessing of the Mauve output to identify good candidates for
functional equivalence, but it's not something currently supported by
Mauve itself.

The use of the term Ortholog in Mauve was a nomenclature mistake made
when developing the feature.

> Last question : is there a way to extract orthologs using a
> command-line program ?

This is available in the snapshots and will be in a future release, but
not in the 2.3.1 release. In the meantime you can get the snapshots
here:
http://gel.ahabs.wisc.edu/mauve/snapshots

You will want to run something like:

java -cp Mauve.jar org.gel.mauve.analysis.OneToOneOrthologExporter


Best,
-Aaron


-- 
Aaron E. Darling, Ph.D.
Associate Professor, ithree institute
University of Technology Sydney
Australia

http://darlinglab.org
twitter: @koadman



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