Replace vcf in-house variant IDs with dnSNP variant IDs
4
1
Entering edit mode
5.6 years ago
willgilks ▴ 310

I have two vcfs from D.melanogaster. The first has in-house variant identifiers, the second contains NCBI-dbSNP variant identifiers. Only the first file has the genotype data. There are 4 million variants in the first file, and 5 million in the second. There is a substantial overlap between the two in terms of what variants are present. How can I replace the in-house variant identifier with the corresponding dbSNP identifier ?

It doesn't seem as though GATK has a tool to do this. I'm browsing around other programs. Otherwise I'll try to write a perl script.

SNP next-gen genome sequencing vcf • 2.3k views
0
Entering edit mode

Hi Ashutosh and Alons, and apologies for the late response,

I used GATK AnnotateVariants the and it seemed to work. I'm using a different vcf now, and it fails, really for these reasons:

2. The dbSNP alleles are stated in alphabetical order, which differs from the reference-alternate allele order in the input vcf.
3. dbSNP indels have a dash as the first allele .. because this base isn't changed.
4. The alternate allele for an indel in dbSNP is always missing the first base, compared with the input vcf.

I thought about trying to import the two files into R and match the IDs there, but they're too big. My current alternative is to match the IDs using bash. I've used SNPeff for other things, and shall try with this task.

The two more frustrating things are that:

1. I went to a lot of effort formatting my vcf for dbSNP submission, and now matching the new IDs to the in-house ones is proving difficult.
2. This process should be a common, critical and standardised process, yet I can't find any code or records for it.

Anyway, thanks again for getting back to me, and I hope to post a solution soon.

0
Entering edit mode

I'm not sure whether I can help you, but would you mind posting examples of the problematic data? Specifically, a couple lines from your custom-made VCF, the dbSNP indel lines, etc. Basically, a couple lines from all of the relevant files, corresponding to the same mutations.

VCF has the incredibly irritating requirement of padding indels with an unrelated nearby base, which is why it differs from dbSNP, but it's not overly difficult to programatically convert from VCF->dbSNP (the other way is harder).

1
Entering edit mode
4.3 years ago
willgilks ▴ 310

Hi Brian,

Thanks for your response. I think I've solved my problem using a few lines of bash. Previously I made a vcf from the dbSNP file, then used this to GATK-annotate the target vcf. With the current method, I just select a few columns. Lines from the input files, and my output are below the code. There is no automated validation, such as checking alleles, length of the output columns, or omitted variants. If you can see any easy improvements, that would be useful.

## From dbSNP information file:
## 1. Remove header and blank rows.
## 2. Select columns containing only old and new variant IDs (2+5).
## 3. Sort by original variant ID (column 1).

grep -v '^#' ${dbsnp_dat} | grep -v -e '^$' | awk '{OFS="\t";print $2,$5}' | sort -k1 > body_${dbsnp_dat} ## Join the input vcf with the dbsnp information, which matches the variant IDs: ## New variant IDs end up being the last column (232), which isn't terrible but it's not ideal. join -t$'\t' -1 3 -2 1 body_${vcf}.txt body_${dbsnp_dat} > joined.txt

## Create first three columns of new vcf file (chromosome, position, variant ID):
## Note here I've made a variant ID column which is a conjugation of the old and new IDs, separated by a semi-colon.

awk '{OFS="\t";print $2,$3,$1";"$232}' joined.txt > first3cols.txt

## Remove unecessary columns from body of temp vcf (Takes a few minutes with 1.7m variants):

cut -f4-231 < joined.txt > other_cols.txt

## Combine the first columns with the remainder, and sort by chromosome and BP. Specification of tab seperator with -t 't' dependent on operating system.
paste first3cols.txt other_cols.txt | sort -k2 -k1 -t 't' > final_body.txt

## Now put header rows on the vcf.


Top rows of my output:

chr3R   15205653        hc_abcdi;rs881319980    G       GT      64059.90        PASS    AC=135;AF=0.311;AN=434;BaseQRankSum=-2.600e-01;ClippingRankSum=-2.800e-02;DP=5447;EFF=UPSTREAM(MODIFIER||3550||632|CG4203|protein_coding|CODING|FBtr0083048||GT),DOWNSTREAM(MODIFIER||2677||503|CG42542|protein_coding|CODING|FBtr03
chrX    19680803        hc_abcdk;rs206315230    G       T       9516.41 PASS    AC=17;AF=0.038;AN=444;BaseQRankSum=0.115;ClippingRankSum=0.181;DP=5421;EFF=UPSTREAM(MODIFIER||4912||645|et|protein_coding|CODING|FBtr0308571||T),UPSTREAM(MODIFIER||3005||547|Ubqn|protein_coding|CODING|FBtr0074750||T),INTRON(MODIFIER||||


Lines from my in-house vcf:

chr2L   21539   hc_nwpsm        T       TATA    10409.49        PASS    AC=49;AF=0.113;AN=434;BaseQRankSum=0.039;ClippingRankSum=0.00;DP=3241;EFF=UPSTREAM(MODIFIER||2970||1161|l_2_gl|protein_coding|CODING|FBtr0078170||TATA),DOWNSTREAM(MODIFIER||283||842|Ir21a|protein_coding|CODING|FBtr0113008||TATA),DOWNSTREAM(MODI
chr2L   22077   hc_nodcb        C       CCAT    123.81  PASS    AC=1;AF=2.252e-03;AN=444;BaseQRankSum=-5.360e-01;ClippingRankSum=-7.840e-01;DP=6341;EFF=CODON_INSERTION(MODERATE||atc/atcATG|I790IM|842|Ir21a|protein_coding|CODING|FBtr0113008|5|CCAT),UPSTREAM(MODIFIER||3508||1161|l_2_gl|protein_coding|CODING|FBtr00781
chr2L   22081   hc_munaj        G       GAAATAACA       65.81   PASS    AC=1;AF=2.252e-03;AN=444;BaseQRankSum=1.58;ClippingRankSum=-2.840e-01;DP=6430;EFF=FRAME_SHIFT(HIGH||gac/gaTGTTATTTc|D789DVI?|842|Ir21a|protein_coding|CODING|FBtr0113008|5|GAAATAACA),UPSTREAM(MODIFIER||3512||1161|l_2_gl|protein_coding|CODING|FBt
chr2L   25378   hc_fueqn        C       T       41734.96        PASS    AC=121;AF=0.275;AN=440;BaseQRankSum=0.157;ClippingRankSum=-2.440e-01;DP=4427;EFF=UPSTREAM(MODIFIER||223||842|Ir21a|protein_coding|CODING|FBtr0113008||T),DOWNSTREAM(MODIFIER||24||1998|Cda5|protein_coding|CODING|FBtr0078164||T),INTERGENIC(MODIFIE
chr2L   25727   hc_jamie        T       G       1342.13 PASS    AC=10;AF=0.023;AN=442;BaseQRankSum=-1.560e-01;ClippingRankSum=0.383;DP=4819;EFF=UTR_3_PRIME(MODIFIER||794||1998|Cda5|protein_coding|CODING|FBtr0078164|14|G),UPSTREAM(MODIFIER||572||842|Ir21a|protein_coding|CODING|FBtr0113008||G);FS=4.030;InbreedingCoef


The same lines from the file provided by dbSNP:

ss1985661068    hc_nwpsm        -/ATA   444     rs881281674     0       2L      21539   NT_033779.5     21539   0       Release_6_plus_ISO1_MT  1
ss1985661069    hc_nodcb        -/CAT   444     rs881341942     0       2L      22077   NT_033779.5     22077   0       Release_6_plus_ISO1_MT  1
ss1985661070    hc_munaj        -/AAATAACA      444     rs881205429     0       2L      22081   NT_033779.5     22081   0       Release_6_plus_ISO1_MT  1
ss1985661071    hc_fueqn        C/T     444     rs881216460     0       2L      25378   NT_033779.5     25378   0       Release_6_plus_ISO1_MT  1
ss1985661072    hc_jamie        G/T     444     rs881333198     0       2L      25727   NT_033779.5     25727   0       Release_6_plus_ISO1_MT  1

2
Entering edit mode
5.6 years ago

If I understood your question GATK's VariantAnnotator may help you. It can take dbSNP vcf file and your vcf file as inputs and append dbSNP rsIDs to your vcf file.

2
Entering edit mode
5.4 years ago
alons ▴ 270

There's a tool we use called SnpSift (under SnPEff project)

It annotates a VCF field of choice (you can choose "id") for variants using a given VCF, which could be dbSNP.

0
Entering edit mode
4.3 years ago

I have done very similar annotation tasks using the BCFtools annotate function