VariantAnnotation (version 1.18.1)

PolyPhenDb-class: PolyPhenDb objects

Description

The PolyPhenDb class is a container for storing a connection to a PolyPhen sqlite database.

Details

PolyPhen (Polymorphism Phenotyping) is a tool which predicts the possible impact of an amino acid substitution on the structure and function of a human protein by applying empirical rules to the sequence, phylogenetic and structural information characterizing the substitution.

PolyPhen makes its predictions using UniProt features, PSIC profiles scores derived from multiple alignment and matches to PDP or PQS structural databases. The procedure can be roughly outlined in the following steps, see the references for complete details,

• sequence-based characterization of substitution site
• calculation of PSIC profile scores for two amino acid variants
• calculation of structural parameters and contacts
• prediction

PolyPhen uses empirically derived rules to predict that a non-synonymous SNP is

• probably damaging : it is with high confidence supposed to affect protein function or structure
• possibly damaging : it is supposed to affect protein function or structure
• benign : most likely lacking any phenotypic effect
• unknown : when in some rare cases, the lack of data do not allow PolyPhen to make a prediction

References

PolyPhen Home: http://genetics.bwh.harvard.edu/pph2/dokuwiki/

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. Nat Methods 7(4):248-249 (2010).

Ramensky V, Bork P, Sunyaev S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res 30(17):3894-3900 (2002).

Sunyaev SR, Eisenhaber F, Rodchenkov IV, Eisenhaber B, Tumanyan VG, Kuznetsov EN. PSIC: profile extraction from sequence alignments with position-specific counts of independent observations. Protein Eng 12(5):387-394 (1999).

See Also

?PolyPhenDbColumns

Examples

library(PolyPhen.Hsapiens.dbSNP131)

## metadata
metadata(PolyPhen.Hsapiens.dbSNP131)

## available rsid's 
head(keys(PolyPhen.Hsapiens.dbSNP131))

## column descriptions found at ?PolyPhenDbColumns
columns(PolyPhen.Hsapiens.dbSNP131)

## subset on keys and columns 
subst <- c("AA1", "AA2", "PREDICTION")
rsids <- c("rs2142947", "rs4995127", "rs3026284")
select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)

## retrieve substitution scores 
subst <- c("IDPMAX", "IDPSNP", "IDQMIN")
select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)

## retrieve the PolyPhen-2 classifiers 
subst <- c("PPH2CLASS", "PPH2PROB", "PPH2FPR", "PPH2TPR", "PPH2FDR")
select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)

## duplicate groups of rsid's
duplicateRSID(PolyPhen.Hsapiens.dbSNP131, c("rs71225486", "rs1063796"))