(SIFT, Polyphen, PROVEAN) vs. (ANNOVAR) vs. (LOFTEE)

Question

[genetic]

Hello,

I am working on functional annotation of my exome-chip variants.

I am not sure what are the differences using annotation from (SIFT, Polyphen, PROVEAN) vs. (ANNOVAR) vs. (LOFTEE).

ANNOVARannotates all SNPs using refseq's sequence information without using any algorithm.

(SIFT, Polyphen, PROVEAN) annotates all SNPs using certain algorithms.

LOFTEE is specific for annotating LoF variants, and(SIFT, Polyphen, PROVEAN) also predict deleterious/disruptive variants.

I guess there is no classical answer to categorize LoF variants, but I would like to know what would be the main differences using those software?

Thank you,

Answer 1

[igor]

That's comparing apples and oranges.

ANNOVAR is a tool for annotating genomic regions. It can annotate using RefSeq info as well as other databases that you mention such as SIFT or Polyphen.

Answer 2

[rbagnall]

SIFT, Polyphen, PROVEAN are tools to predict if a missense variant has an impact on protein function and can play a small role in deciding if a variant is of clinical significance (pathogenic). SIFT and Provean may additionally make predictions about insertions and deletions (indels).

ANNOVAR is a tool to annotate variants by different classes; eg [coding transcript, non coding transcript, intergenic] and [missense, nonsense, splice site, 5'UTR, 3'UTR, intronic, non-coding] and [frequency in general population] and [evolutionary conservation score of the nucleotide, GERP] and [physiochemical change in amino acid, Grantham score] etc. It queries many different data sets of such annotations. Annovar annotations can include SIFT, polyphen and provean if you wish.

As you say, LOFTEE is specific for annotation of loss of function variants.

[Shicheng Guo]

Hope to know is there pre-calculated LOFTEE annotation publicly?

[predeus]

Take a look at dbNSFP