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

Methods

In the code below, x is a PolyPhenDb object.

metadata(x): Returns x's metadata in a data frame.

columns(x): Returns the names of the columns that can be used to subset the data columns. For column descriptions see ?PolyPhenDbColumns.

keys(x): Returns the names of the keys that can be used to subset the data rows. The keys values are the rsid's.

select(x, keys = NULL, columns = NULL, ...): Returns a subset of data defined by the character vectors keys and columns. If no keys are supplied, all rows are returned. If no columns are supplied, all columns are returned. See ?PolyPhenDbColumns for column descriptions.

duplicateRSID(x): Returns a named list of duplicate rsid groups. The names are the keys, the list elements are the rsid's that have been reported as having identical chromosome position and alleles and therefore translating into the same amino acid residue substitution.

Author(s)

Valerie Obenchain

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"))

Results

R version 3.3.1 (2016-06-21) -- "Bug in Your Hair"
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Type 'demo()' for some demos, 'help()' for on-line help, or
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> library(VariantAnnotation)
Loading required package: BiocGenerics
Loading required package: parallel

Attaching package: 'BiocGenerics'

The following objects are masked from 'package:parallel':

    clusterApply, clusterApplyLB, clusterCall, clusterEvalQ,
    clusterExport, clusterMap, parApply, parCapply, parLapply,
    parLapplyLB, parRapply, parSapply, parSapplyLB

The following objects are masked from 'package:stats':

    IQR, mad, xtabs

The following objects are masked from 'package:base':

    Filter, Find, Map, Position, Reduce, anyDuplicated, append,
    as.data.frame, cbind, colnames, do.call, duplicated, eval, evalq,
    get, grep, grepl, intersect, is.unsorted, lapply, lengths, mapply,
    match, mget, order, paste, pmax, pmax.int, pmin, pmin.int, rank,
    rbind, rownames, sapply, setdiff, sort, table, tapply, union,
    unique, unsplit

Loading required package: GenomeInfoDb
Loading required package: stats4
Loading required package: S4Vectors

Attaching package: 'S4Vectors'

The following objects are masked from 'package:base':

    colMeans, colSums, expand.grid, rowMeans, rowSums

Loading required package: IRanges
Loading required package: GenomicRanges
Loading required package: SummarizedExperiment
Loading required package: Biobase
Welcome to Bioconductor

    Vignettes contain introductory material; view with
    'browseVignettes()'. To cite Bioconductor, see
    'citation("Biobase")', and for packages 'citation("pkgname")'.

Loading required package: Rsamtools
Loading required package: Biostrings
Loading required package: XVector

Attaching package: 'VariantAnnotation'

The following object is masked from 'package:base':

    tabulate

> png(filename="/home/ddbj/snapshot/RGM3/R_BC/result/VariantAnnotation/PolyPhenDb-class.Rd_%03d_medium.png", width=480, height=480)
> ### Name: PolyPhenDb-class
> ### Title: PolyPhenDb objects
> ### Aliases: PolyPhen PolyPhenDb class:PolyPhenDb PolyPhenDb-class
> ###   duplicateRSID metadata,PolyPhenDb-method columns,PolyPhenDb-method
> ###   keys,PolyPhenDb-method select,PolyPhenDb-method
> ### Keywords: classes methods
> 
> ### ** Examples
> 
> library(PolyPhen.Hsapiens.dbSNP131)
Loading required package: RSQLite
Loading required package: DBI
> 
> ## metadata
> metadata(PolyPhen.Hsapiens.dbSNP131)
                              name
1                          Db type
2                      Data source
3                           Genome
4                Genus and Species
5                     Resource URL
6                      dbSNP build
7                    Creation time
8 RSQLite version at creation time
9                          package
                                                    value
1                                              PolyPhenDb
2                                               PolyPhen2
3                                                    hg19
4                                            Homo sapiens
5 http://genetics.bwh.harvard.edu/pph2/dokuwiki/downloads
6                                                     131
7            2012-03-13 16:16:18 -0700 (Tue, 13 Mar 2012)
8                                                  0.11.1
9                                       VariantAnnotation
> 
> ## available rsid's 
> head(keys(PolyPhen.Hsapiens.dbSNP131))
[1] "rs10000692" "rs10001580" "rs10002700" "rs10003238" "rs10003369"
[6] "rs10004"   
> 
> ## column descriptions found at ?PolyPhenDbColumns
> columns(PolyPhen.Hsapiens.dbSNP131)
 [1] "AA1"         "AA2"         "ACC"         "AVENHET"     "AVENINT"    
 [6] "AVENSIT"     "BASEDON"     "BFACT"       "CODPOS"      "COMMENTS"   
[11] "CPG"         "DPROP"       "DSCORE"      "DVOL"        "EFFECT"     
[16] "HBONDS"      "IDENT"       "IDPMAX"      "IDPSNP"      "IDQMIN"     
[21] "LENGTH"      "MAPREG"      "MINDHET"     "MINDINT"     "MINDJNC"    
[26] "MINDSIT"     "NFILT"       "NOBS"        "NORMACC"     "NSTRUCT"    
[31] "NT1"         "NT2"         "OAA1"        "OAA2"        "OACC"       
[36] "OPOS"        "OSNPID"      "PDBCH"       "PDBID"       "PDBPOS"     
[41] "PFAMHIT"     "PHAT"        "POS"         "PPH2CLASS"   "PPH2FDR"    
[46] "PPH2FPR"     "PPH2PROB"    "PPH2TPR"     "PREDICTION"  "REGION"     
[51] "RSID"        "SCORE1"      "SCORE2"      "SECSTR"      "SITE"       
[56] "SNPID"       "TRAININGSET" "TRANSV"     
> 
> ## subset on keys and columns 
> subst <- c("AA1", "AA2", "PREDICTION")
> rsids <- c("rs2142947", "rs4995127", "rs3026284")
> select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)
       RSID AA1 AA2        PREDICTION
1 rs2142947   F   L            benign
2 rs4995127   F   L probably damaging
3 rs4995127   F   L possibly damaging
4 rs3026284   G   D probably damaging
> 
> ## retrieve substitution scores 
> subst <- c("IDPMAX", "IDPSNP", "IDQMIN")
> select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)
       RSID IDPMAX IDPSNP IDQMIN
1 rs2142947 33.979 33.979 63.615
2 rs2142947 32.679 32.679 61.181
3 rs2142947 33.355 33.355 62.447
4 rs2142947     NA     NA     NA
5 rs4995127  2.155     NA 61.715
6 rs4995127  2.177     NA 62.343
7 rs4995127     NA     NA     NA
8 rs3026284  2.233     NA 69.349
9 rs3026284     NA     NA     NA
> 
> ## retrieve the PolyPhen-2 classifiers 
> subst <- c("PPH2CLASS", "PPH2PROB", "PPH2FPR", "PPH2TPR", "PPH2FDR")
> select(PolyPhen.Hsapiens.dbSNP131, keys=rsids, columns=subst)
        RSID   PPH2CLASS PPH2PROB PPH2FPR PPH2TPR PPH2FDR
1  rs2142947     neutral    0.070  0.2000   0.929   0.300
2  rs2142947     neutral    0.018  0.2520   0.952   0.345
3  rs2142947     neutral    0.007  0.3010   0.966   0.383
4  rs2142947        <NA>    0.118  0.4140   0.912      NA
5  rs2142947        <NA>    0.043  0.5070   0.947      NA
6  rs2142947        <NA>    0.019  0.5810   0.964      NA
7  rs4995127 deleterious    0.970  0.0629   0.694   0.153
8  rs4995127        <NA>    0.803  0.1860   0.720      NA
9  rs3026284 deleterious    0.936  0.0746   0.737   0.168
10 rs3026284        <NA>    0.919  0.1330   0.636      NA
> 
> ## duplicate groups of rsid's
> duplicateRSID(PolyPhen.Hsapiens.dbSNP131, c("rs71225486", "rs1063796"))
$rs71225486
[1] "rs76416839"

$rs1063796
[1] "rs17039307" "rs78671912"

> 
> 
> 
> 
> 
> dev.off()
null device 
          1 
>