[ensembl-dev] Precomputed SIFT/Polyphen2 Scores on Ensembl

[Graham Ritchie]

Hi Mark,

When pre-computing the SIFT and PolyPhen scores we download the software and run the tools locally using our own copies of the UniProt, Pfam, PDB, DSSP (etc.) databases which we update when we start the pipeline, so it is unlikely we will run the tools using exactly the same source data as the web applications (though we follow the author's instructions as closely as possible to try to ensure that results are reproducible). We also always supply the ensembl translation for each transcript as the reference protein, we don't try to find the closest UniProt protein or anything. The web applications may also use newer versions of the software than we ran, in particular for release 62 (and the forthcoming release 63) we used PolyPhen version 2.0.23, while the web application uses the newer version 2.1.0. You can find details of the version we ran, and the source databases we used, on the variation documentation page here:

http://www.ensembl.org/info/docs/variation/index.html#nsSNP

All of these factors mean we are unlikely to produce exactly the same scores as the web applications, but if you are finding significant differences then this is something we should look into, in particular if you find that you have lots of cases where the qualitative predictions ('benign', 'tolerated', 'probably damaging' etc.) differ between ensembl and the web applications then we will certainly investigate.

Hope that makes things clearer.

Cheers,

Graham

Ensembl Variation


On 16 Jun 2011, at 18:02, Mark Aquino wrote:

> Hi,
> 
> Does anyone know why the precomuted SIFT and Polyphen-2 scores on the Ensembl-variation database differ from the scores returned for the same variations on their respective web-applications?
> 
> -Mark Aquino
> 
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