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SnpSift dbNSFP

The dbNSFP is an integrated database of functional predictions from multiple algorithms (SIFT, Polyphen2, LRT and MutationTaster, PhyloP and GERP++, etc.).

Typical usage

One of the main advantages is that you can annotate using multiple prediction tools with just one command. This allows for faster annotations. Here is the link to dbNSFP database website for more details.

Database: In order to annotate using dbNSFP, you need to download the dbNSFP database and the index file. dbNSFP is large (several GB) so it might take a while to download it. The database is compressed (block-gzip) and tabix-indexed, so two files are required (the data .gz file and the .gz.tbi index file).

You can download the files from SnpEff's site (remember that you need both the database and the index file):

  • GRCh37 / hg19 (dbNSFP Academic):
    • Database. Save file as dbNSFP.txt.gz
    • Index. Save file as dbNSFP.txt.gz.tbi
  • GRCh38 / hg38 (dbNSFP Academic):
    • Database. Save file as dbNSFP.txt.gz
    • Index. Save file as dbNSFP.txt.gz.tbi

dbNSFP Annotation example

Here is a full example how to perform annotations:

# Annotate using dbNSFP
# Note that the first time you run the command, it will attempt to download the dbNSFP database.
java -jar SnpSift.jar dbnsfp -v myFile.vcf > myFile.annotated.vcf

Info

You can now specify which fields you want to use for annotation using the -f command line option followed by a comma separated list of field names. Defaults fields are shown when running the command without any arguments java -jar SnpSift.jar dbNSFP

If your dbNSFP file is not in the 'default' path (where SnpEff expects it), you can specify the path to your dbNSFP file using the -db command line option:

# Annotate using dbNSFP
java -jar SnpSift.jar dbnsfp -v -db path/to/my/dbNSFP2.9.txt.gz myFile.vcf > myFile.annotated.vcf

Building dbNSFP (for developers)

Info

Users do NOT need to do this, since a pre-indexed database can be downloaded from SnpSift's site (see previous sub-section). These instructions are mostly for developers.

You can also create dbNSFP files yourself, downloading the files from DbNsfp site. Two files are required:

  • A block-gzipped database file
  • The corresponding tabix index for the database file.

Creating a file that SnpSift can use is simple, just follow this guideline: 

# Download dbNSFP database
$ wget http://dbnsfp.houstonbioinformatics.org/dbNSFPzip/dbNSFP2.9.zip

# Uncompress
$ unzip dbNSFP2.9.zip

# Create a single file version
$ (head -n 1 dbNSFP2.9_variant.chr1 ; cat dbNSFP2.9_variant.chr* | grep -v "^#" ) > dbNSFP2.9.txt

# Compress using block-gzip algorithm
bgzip dbNSFP2.9.txt

# Create tabix index
tabix -s 1 -b 2 -e 2 dbNSFP2.9.txt.gz

Building dbNSFP for hg19/GRCh37 using dbNSFP 3.X:

Latest dbNSFP versions (3.X) are based on GRCh38/hg38 genomic coordinates. In order to use the latest dbNSFP databses with GRCh37/hg19 genome versions you need to create a new dbNSFP file with the right coordinates. Fortunately, dbNSFP 3.X provides GRCh37/hg19 coordinates, so we only need to swap coordinates and sort by genomic position. You can easily do this by using the dbNSFP_sort.pl script (you can find it here) by running something like the following command lines: 

# Set to your downloaded dbNSFP version
version="3.2a"

# Replace coordinates by columns 7 and 8 (hg19 coordinates) and sort by those coordinates
cat dbNSFP${version}_variant.chr* \
    | $HOME/snpEff/scripts_build/dbNSFP_sort.pl 7 8 \
    > dbNSFP${version}_hg19.txt

# Compress and index
bgzip dbNSFP${version}_hg19.txt
tabix -s 1 -b 2 -e 2 dbNSFP${version}_hg19.txt.gz