Prediction of the functional effect of nsSNPs

Question

[Sabine]

Dear All,

I am doing few histone protein's SNP analysis.

I have used SIFT and Polyphen for my initial analysis. Now I would like predict its functional impact.

Can anyone please suggest me few tools or software for the prediction of the functional

effect of nsSNPs. Thank you

Answer 1

[Pablo]

You can try SnpEff + SnpFit (dbNFSP)

NOTE: RamRs noted that the input data format is NOT from a sequencing experiment, but another format that lacks of the corresponding genomic coordinates. In such case, this recommendation is not appropriate for the analysis.

[Ram]

SnpSift, you mean. Also, aren't these tools to use at VCF level? I think OP wants to go from AA mut to possible functional impact.

[Pablo]

Indeed. The question mentions "protein SNP analysis", so I'm assuming these are from sequencing data (otherwise it would be something like "protein polymorphism analysis"). May be sana can clarify a little bit more in the formats being used for the analysis...

[Ram]

"Protein polymorphism"? People use the term SNP without realizing they should be using mutation/variant - from my observation. I'm quite certain OP is referring a general variant/mutation and not a single nucleotide polymorphism.

[Denise CS]

In Ensembl, we avoid using the term mutation unless the positions come from COSMIC and HGMD which are mutation databases. We use the term 'variants' instead...

[Ram]

I agree. Calling AA variants "mutations" is more of my workplace convention than a general purpose terminology.

[Pablo]

OK, my bad then. I'll try to delete / edit this answer.

[Ram]

All inputs help. In our field, out needs change everyday, no? I'm pretty sure OP will run into snpEff/SnpSift/VEP requirements soon enough :-)

Answer 2

[a.polo88]

This is a good question. there are many other tools to investigate the functional effect of the SNPs.

In first instance you can model the SNPs into your protein structure of interest simple using the homology modeling (using mutate_model that you can get from the website of modeller) once you obtain your structure with the point mutation you can perform three type of analysis using three bioinformatics tools:

DSSP you can assign secondary structure both wild-type and to the variant protein and than you compare if there are a differences in the secondary structure(note that DSSP do not predict the secondary structure but only assign a possible structure)

HBPLUS you can use this tool to perform the analysis of the hydrogen bond to evaluate the pattern of hydrogen bond

NACCESS you can use this tools to evaluate the accessible areas of the molecule

If you have any questions can contact me

[Sabine]

Thank you for the detailed reply..let me go through these..

Answer 3

[Denise CS]

The Perl script version of the Ensembl VEP has got a few plugins e.g. CADD, Condel and dbNSFP that can help you to predict the functional consequence of variants on Ensembl (and RefSeq) genes and transcripts.

Answer 4

[Ram]

Have you tried PredictSNP?

[Sabine]

No..Let me try...thanks