BCF Tools Filter on 1000Genomes Annotation

Question

[jon.klonowski]

I am trying to filter a VCF based on the allele frequency as given by ANNOVAR annotation, which has annotations in the info column. I am doing this because I only want the rare variants for analysis. I have been trying bcf query but it is not acting well behaved....

$ bcftools view -i 'INFO/controls_AF_popmax < 0.05' File_Name.vcf.gz  | bgzip > output.vcf.gz

or

$ bcftools query File_Name.vcf.gz -f '%ID\t %INFO/Gene.ensGene\t %INFO/controls_AF_popmax\n' -i 'INFO/controls_AF_popmax < 0.05' >  output.vcf

I get output but not wat expected in terms of the filter.

I want a vcf in the end so I can make ped, map, bed, bim, fam from it using PLINK (I know how to do that part).

UPDATE: I thoguht maybe it was because of the format of the INFO/controls_AF_popmax field in the header. I tried to change the designation to the same designation AF is but that did not work either.

UPDATE: It works for 'INFO/AF > 0.05' but not for 'INFO/controls_AF_popmax > 0.05' do not know why

[finswimmer]

Hello,

could you please show us the complete header and some variants of your input file?

fin swimmer

[jon.klonowski]

Looks like there were numerous extra info fields specified in the header that were not actually present. I just purged them, going to double check the header and try this all again.

UPDATE:

AFTER UPDATING INFO IT THE IT APPEARS TO BE WORKING. Lets see

what I changed:

1. removed superfluous headers
2. Changed format of the Annotation of interested to Float from String:

---

## INFO=<ID=controls_AF_popmax,Number=.,Type=Float,Description="controls_AF_popmax annotation provided by ANNOVAR">

[Monete R. Gomes]

Hi

I had same problem on my vcf.

I also wanted to filter a VCF based on the allele frequency as given by ANNOVAR annotation. Like you said, I've changed my vcf INFO header (from "String" to "Float", only on site which I wanted to filter) and bcftools query (only) worked fine. BTW... excellent comment! Thank you very much!

From:

##INFO=<ID=ExAC_EAS,Number=.,Type=String,Description="ExAC_EAS annotation provided by ANNOVAR">

To:

##INFO=<ID=ExAC_EAS,Number=.,Type=Float,Description="ExAC_EAS annotation provided by ANNOVAR">

Command:

bcftools query input_edited.vcf -f '%CHROM\t%POS\t%ID\t%REF\t%ALT\t%INFO/ExAC_EAS\n' -i 'INFO/ExAC_EAS != "." & INFO/ExAC_EAS < 0.005'

With this command, my output is tabular.

I also tried bcftools view (to get a vcf output) and didn't work:

bcftools view -e 'ExAC_EAS="." & ExAC_EAS > 0.005' input_edited.vcf

I had a lot of errors like this: [W::vcf_parse_format]

I did some tests with 2 versions of vcf: before and after this modification. The error is still there in both cases.

I think the steps here are: use bcftools query, get ID's from variants of interest (in tabular format), use these ID's as query again against my original vcf to get variants in VCF format.

[jon.klonowski]

UPDATED VCF header where i deleted all the contig information and filtering information so it would fit in a single screenshot:

PREVIOUS VCF HEADER https://ibb.co/rZRtR7F

UPDATED VCF HEADER https://ibb.co/n8cWxm9

Sorry i am not sure the best way to share...

and here is a record, not including sample information:

chr1    861219  chr1:861219:G:C G   C   490.79  PASS    AC=0;AF=0.0007669;AN=922;BaseQRankSum=2.72;DP=18855;ExcessHet=3.0103;FS=3.736;InbreedingCoeff=-0.0011;MLEAC=1;MLEAF=0.0007669;MQ=60;MQRankSum=0;QD=18.88;ReadPosRankSum=0.416;SOR=2.247;VQSLOD=13.64;culprit=MQRankSum;ANNOVAR_DATE=2018-04-16;Func.refGene=intronic;Gene.refGene=SAMD11;GeneDetail.refGene=.;ExonicFunc.refGene=.;AAChange.refGene=.;Func.ensGene=intronic;Gene.ensGene=ENSG00000187634;GeneDetail.ensGene=.;ExonicFunc.ensGene=.;AAChange.ensGene=.;AF=0.0001;AF_popmax=0.0004;AF_male=0.0001;AF_female=0.0001;AF_raw=0.0001;AF_afr=0;AF_sas=0.0004;AF_amr=0;AF_eas=0;AF_nfe=0.0001;AF_fin=0;AF_asj=0.0002;AF_oth=0;non_topmed_AF_popmax=0.0004;non_neuro_AF_popmax=0.0004;non_cancer_AF_popmax=0.0004;controls_AF_popmax=0.0003;MCAP13=.;CADD13_RawScore=.;CADD13_PHRED=.;gerp++elem=.;CLNALLELEID=.;CLNDN=.;CLNDISDB=.;CLNREVSTAT=.;CLNSIG=.;ALLELE_END GT:AD:DP:GQ:PL

[jon.klonowski]

i will try to clean up my header completely and double check the positioning, maybe the annovar annotation didnt properly align the header and that is why i am getting the issue