convert genome coordinates from b36 to hg19

Question

[@anna]

Hi there,

I have an old bed and vcf files that were created using the genome reference b36. Is there any way to update the genome coordinates to GRCh37/hg19?

Many thanks in advance, Anna

[Pierre Lindenbaum]

ucsc liftover and picard liftovervcf

[@anna]

I tried with picard liftovervcf, but it gives me an empty file (it only has the header lines), while all variants go to the rejected_variants.vcf

java -jar picard.jar LiftoverVcf I=chr11.vcf O=chr11b.vcf CHAIN=hg18ToHg19.over.chain REJECT=rejected_variants.vcf R=ucsc.hg19.fasta

[Pierre Lindenbaum]

check the chromosome nomenclature (chr1 vs 1)

[@anna]

Yes, that was it. Silly mistake sorry

Still, the output file has 237.905 lines and the rejected_variants file has 436.954 lines, which seems a lot. Is it expectable?

It also gives me this warning: WARNING LiftoverVcf 137518 variants with a swapped REF/ALT were identified, but were not recovered.

Answer 1

[vkkodali_ncbi]

NCBI remap service can be used for this. Specifically, you can use this link with the combination of source (NCBI36/hg18) and target (GRCh37/hg19) assemblies selected.

[@anna]

I have also tried this link. But when uploading the file to the Michigan Imputation Server, it gives the following error:

Unable to parse header with error: Your input file has a malformed header: We never saw the required CHROM header line (starting with one #) for the input VCF file

and my vcf does have the #CHROM header:

line 44: #CHROM POS ID REF ALT QUAL FILTER INFO FORMAT 4023 (...)

line 45: 10 111955 rs7909677 A G . PASS PR;REMAP_ALIGN=FP GT 0/0 (...)

[vkkodali_ncbi]

Did you paste the contents of the VCF in remap web interface or upload a file? I am wondering if it has something to do with using space vs tab as delimiters. An example file, if possible, will be helpful to diagnose the issue.

[@anna]

I uploaded the file. Can you please tell me how to upload the file here?

##fileformat=VCFv4.2                                    
##FILTER=<ID=PASS,Description="All filters passed">                                 
##fileDate=20220228                                 
##source=PLINKv1.90                                 
##contig=<ID=0,length=2147483645>                                   
##contig=<ID=1,length=247137335>                                    
##contig=<ID=2,length=242697434>                                    
##contig=<ID=3,length=199340831>                                    
##contig=<ID=4,length=191167889>                                    
##contig=<ID=5,length=180625440>                                    
##contig=<ID=6,length=170747903>                                    
##contig=<ID=7,length=158809727>                                    
##contig=<ID=8,length=146264219>                                    
##contig=<ID=9,length=140191297>                                    
##contig=<ID=10,length=135237858>                                   
##contig=<ID=11,length=134449983>                                   
##contig=<ID=12,length=132209175>                                   
##contig=<ID=13,length=114125099>                                   
##contig=<ID=14,length=106356483>                                   
##contig=<ID=15,length=100217561>                                   
##contig=<ID=16,length=88690777>                                    
##contig=<ID=17,length=78643089>                                    
##contig=<ID=18,length=76116030>                                    
##contig=<ID=19,length=63786939>                                    
##contig=<ID=20,length=62382908>                                    
##contig=<ID=21,length=46909249>                                    
##contig=<ID=22,length=49565873>                                    
##contig=<ID=23,length=154578240>                                   
##contig=<ID=24,length=27167582>                                    
##contig=<ID=25,length=154881767>                                   
##contig=<ID=26,length=15609>                                   
##INFO=<ID=PR,Number=0,Type=Flag,Description="Provisional reference allele, may not be based on real reference genome">                                 
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">                                    
##bcftools_filterVersion=1.10.2+htslib-1.10.2                                   
##bcftools_filterCommand=filter -r 10 EPI.vcf.gz; Date=Mon Feb 28 12:17:19 2022                                 
##INFO=<ID=REMAP_ALIGN,Number=1,Type=String,Description="Alignment type used for remapping (FP=first pass, SP=second pass)">                                    
##INFO=<ID=REF_EDIT,Number=0,Type=Flag,Description="REF base modified during remapping due to either left shifting or difference in REF base between source and target assemblies.">                                    
##NCBI_remap_source_assm="GCF_000001405.12"                                 
##NCBI_remap_target_assm="GCF_000001405.13"                                 
##NCBI_remap_align_date="2014-09-23 20:19:00"                                   
##NCBI_remap_run_date="2022-02-28T08:24:12"                                 
##NCBI_remap_batch_id="86373"                                   
##NCBI_remap_align_parameters=<minratio=0.5,maxratio=2,multiloc=Y,mergefrag=N>                                  
#CHROM  POS ID  REF ALT QUAL    FILTER  INFO    FORMAT  4023
10  111955  rs7909677   A   G   .   PASS    PR;REMAP_ALIGN=FP   GT  0/0

Is it ok like this, or should I upload the file another way?

[GenoMax]

You can't upload files here but you could post a test section on pastebin.com or upload the raw data file to github.com and then paste a link for that page here.

[@anna]

While doing that, I noticed that at the end of the file, I had a few lines with other chromosomes (eg, HSCHRUN_RANDOM_CTG15). After removing them, the imputation worked.

Again, my original file with only chr11 had 33.421 lines and my remapped file has 12.055. Is it expectable to lose that many variants?