ExAC originally released a VCF that contained the aggregate data for all samples.
It has INFO fields for AFR, AMR, EAS, FIN, NFE, OTH, and SAS populations
along with the combined Adj count.
Recently, 2 additional VCF's that contain only non pyschiatric and only non TCGA samples
have been released.
Here, we will use vcfanno to decorate the original VCF with the alternate counts,
chromosome counts, number of hets, number of hom alts, and allele frequencies of all populations
from each of the 2 additional VCFs. Since the original VCF contains only allele counts, we will
also use vcfanno to calculate the allele frequency for the original, full population. Finally,
we'll calculate the maximum allele frequency from all populations as that is very useful for
filtering.
Creating a conf file can be cumbersome, but in this case, it's simple, if repetitive. As such
we write a script to create a block like this:
[[annotation]]
file="ExAC.r0.3.nonpsych.sites.tidy.vcf.gz"
fields=["AC_AFR","AN_AFR","Hom_AFR","Het_AFR","AC_AMR","AN_AMR","Hom_AMR","Het_AMR","AC_Adj","AN_Adj","AC_EAS","AN_EAS","Hom_EAS","Het_EAS","AC_FIN","AN_FIN","Hom_FIN","Het_FIN","AC_NFE","AN_NFE","Hom_NFE","Het_NFE","AC_OTH","AN_OTH","Hom_OTH","Het_OTH","AC_SAS","AN_SAS","Hom_SAS","Het_SAS"]
ops=["self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self","self"]
names=["nonpsych_AC_AFR","nonpsych_AN_AFR","nonpsych_Hom_AFR","nonpsych_Het_AFR","nonpsych_AC_AMR","nonpsych_AN_AMR","nonpsych_Hom_AMR","nonpsych_Het_AMR","nonpsych_AC_Adj","nonpsych_AN_Adj","nonpsych_AC_EAS","nonpsych_AN_EAS","nonpsych_Hom_EAS","nonpsych_Het_EAS","nonpsych_AC_FIN","nonpsych_AN_FIN","nonpsych_Hom_FIN","nonpsych_Het_FIN","nonpsych_AC_NFE","nonpsych_AN_NFE","nonpsych_Hom_NFE","nonpsych_Het_NFE","nonpsych_AC_OTH","nonpsych_AN_OTH","nonpsych_Hom_OTH","nonpsych_Het_OTH","nonpsych_AC_SAS","nonpsych_AN_SAS","nonpsych_Hom_SAS","nonpsych_Het_SAS"]
And a similar one for nonTCGA. Then, we create a section like this:
[[postannotation]]
fields=["nonpsych_AC_NFE", "nonpsych_AN_NFE"]
name="nonpsych_af_NFE"
op="div2"
type="Float"
for each population and for the original superset as well as for nonpsych, nonTCGA. The script to create all this automatically is here
Then we have a final section that calculates the maximum allele frequency among all populations:
[[postannotation]]
fields=["af_AFR", "af_AMR", "af_EAS", "af_FIN", "af_NFE", "af_OTH", "af_SAS", "nonTCGA_af_AFR", "nonTCGA_af_AMR", "nonTCGA_af_EAS", "nonTCGA_af_FIN", "nonTCGA_af_NFE", "nonTCGA_af_OTH", "nonTCGA_af_SAS", "nonpysch_af_AFR", "nonpysch_af_AMR", "nonpysch_af_EAS", "nonpysch_af_FIN", "nonpysch_af_NFE", "nonpysch_af_OTH", "nonpysch_af_SAS"]
op="max"
name="max_af_ALL"
type="Float"
The entire conf file is here
Then, the vcfanno command is very simple:
vcfanno -p 8 exac_combine.conf ExAC.r0.3.sites.vep.tidy.vcf.gz | bgzip -c > ExAC.r0.3.all.tidy.vcf.gz
This runs in about 15 minutes (10K variants / second) on good server with fast disk.