Question: Conservation At Amino Acid Level
1
gravatar for Biomed
8.0 years ago by
Biomed4.7k
Bethesda, MD, USA
Biomed4.7k wrote:

We annotate exome variants with conservation status using sources like PhyloP, GERP but these query the nucleotide instead of the amino acid. As the nucleotide may not be conserved among species, but the amino acid can be we would like to annotate our variants with amino acid level conservation. What database/UCSC track/reqource we can use to annotate this data into our variants? Thanks

conservation annotation • 2.8k views
ADD COMMENTlink written 8.0 years ago by Biomed4.7k

This is something I have been discussing recently with colleagues. As far as I know there are no conservation tracks based on the amino acid rather than nucleotide level. I'd be happy to stand corrected. If this is indeed the case I imagine it would not be too hard to convert nucleotide convervation scores into amino acid conservation scores. Not trivial but a cool project that would provide a very useful community resource.

ADD REPLYlink written 8.0 years ago by Rubal7770
2
gravatar for Sean Davis
8.0 years ago by
Sean Davis26k
National Institutes of Health, Bethesda, MD
Sean Davis26k wrote:

You might want to look at several methods, such as SIFT, that use amino acid conservation to predict the effects of a change. This isn't a direct answer to your question, but I'm just guessing that the reason you want AA conservation is to help prioritize variants with respect to likely biological impace.

ADD COMMENTlink written 8.0 years ago by Sean Davis26k

Hi Sean, yes the idea is to help prioritize variants but the problem arises when the nucleotide is not so well conserved yet there is stronger conservation at the amino acid levels. I suspect the methods that are based on nucleotide conservation will give a slightly different result in those cases.

ADD REPLYlink written 8.0 years ago by Biomed4.7k

Most of these methods are based on AA conservation, not base-level conservation. I thought that was what you were asking about, but perhaps I misunderstood your qustion?

ADD REPLYlink written 8.0 years ago by Sean Davis26k

You are right I am interested in amino acid-protein level conservation as well as base level conservation. Thanks for the answer.

ADD REPLYlink written 8.0 years ago by Biomed4.7k
0
gravatar for Leszek
8.0 years ago by
Leszek4.0k
IIMCB, Poland
Leszek4.0k wrote:

Hi, Biomed, I assume you work with human data, am I right?
Try PhylomeDB - they provide Maximum likelihood trees and alignments for all human proteins using various species scopes. And yes, all is protein orientated. But you would need to calculated conservation score yourself. I did similar stuff for yeast SNPs, in order to prioritise wet experiments to nonsynonymous SNPs in highly conserved sites. Let me know if you are interested, I can help you with that.

ADD COMMENTlink written 8.0 years ago by Leszek4.0k
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