Liftover Picard hg19 to hg38: variants were not successfully lifted over

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Andres Caballero

• December 09, 2022 18:39

I am trying to convert a sample vcf file from GRCh37 that comes with the VEP installation to see how this tool works, but for some unknown reason, it is not working for me. I have also tried with another smaller test vcf file..but same luck.

a) GATK version used: v4.3.0.0-12 and Picard Version: 2.27.5

b) Exact command used:

java -Xmx8g -jar ~/picard/picard.jar LiftoverVcf \
    I=input/homo_sapiens_hg19.vcf \
    O=output/test_hg19_lifted.vcf \
    CHAIN=hg19ToHg38.over.chain.gz \
    REJECT=output/rejected_vars.vcf \
    R=/root/.vep/homo_sapiens/Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz

c) Entire program log:

Executing as ...@... on Linux 5.15.0-56-generic amd64; OpenJDK 64-Bit Server VM 1.8.0_152-release-1056-b12; Deflater: Intel; Inflater: Intel; Provider GCS is not available; Picard version: 2.27.5
INFO    2022-12-09 18:31:41    LiftoverVcf    Loading up the target reference genome.
INFO    2022-12-09 18:32:15    LiftoverVcf    Lifting variants over and sorting (not yet writing the output file.)
INFO    2022-12-09 18:32:15    LiftoverVcf    Processed 173 variants.
INFO    2022-12-09 18:32:15    LiftoverVcf    173 variants failed to liftover.
INFO    2022-12-09 18:32:15    LiftoverVcf    0 variants lifted over but had mismatching reference alleles after lift over.
INFO    2022-12-09 18:32:15    LiftoverVcf    100.0000% of variants were not successfully lifted over and written to the output.
INFO    2022-12-09 18:32:15    LiftoverVcf    liftover success by source contig:
INFO    2022-12-09 18:32:15    LiftoverVcf    21: 0 / 37 (0.0000%)
INFO    2022-12-09 18:32:15    LiftoverVcf    22: 0 / 136 (0.0000%)
INFO    2022-12-09 18:32:15    LiftoverVcf    lifted variants by target contig:
INFO    2022-12-09 18:32:15    LiftoverVcf    no successfully lifted variants
WARNING    2022-12-09 18:32:15    LiftoverVcf    0 variants with a swapped REF/ALT were identified, but were not recovered.  See RECOVER_SWAPPED_REF_ALT and associated caveats.
INFO    2022-12-09 18:32:15    LiftoverVcf    Writing out sorted records to final VCF.
[Fri Dec 09 18:32:15 UTC 2022] picard.vcf.LiftoverVcf done. Elapsed time: 0.57 minutes.
Runtime.totalMemory()=3167748096

d) This is the head of the output vcf file:

##fileformat=VCFv4.2
##INFO=<ID=ReverseComplementedAlleles,Number=0,Type=Flag,Description="The REF and the ALT alleles have been reverse complemente
d in liftover since the mapping from the previous reference to the current one was on the negative strand.">
##INFO=<ID=SwappedAlleles,Number=0,Type=Flag,Description="The REF and the ALT alleles have been swapped in liftover due to chan
ges in the reference. It is possible that not all INFO annotations reflect this swap, and in the genotypes, only the GT, PL, an
d AD fields have been modified. You should check the TAGS_TO_REVERSE parameter that was used during the LiftOver to be sure.">
##contig=<ID=1,length=248956422>

.....

ANY IDEAS PLEASE?

2

• 

  Andres Caballero

  • December 30, 2022 10:24

  In case someone finds this post, I finally managed to solve it by using a different chain file downloaded from Ensembl (GRCh37_to_GRCh38.chain.gz). The one I was using (downloaded from UCSC) was the one causing the issue. 

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• 

  Crispy13

  • January 05, 2023 08:14

  Download link:

  https://ftp.ensembl.org/pub/assembly_mapping/homo_sapiens/

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• 

  Hassan Alikhani

  • September 08, 2023 11:11

  Same problem here. Considering your note on using the GRCh37_to_GRCh38.chain.gz chain file, I found that the issue is related to chromosome names. If chromosome names in your VCF are like 1, 2, X, M, etc., you can't use the hg19ToHg38.over.chain.gz chain file. There are two solutions:

  1. Change chromosome names in the VCF using bcftools annotate --rename-chrs.
  2. Use GRCh37_to_GRCh38.chain.gz instead of hg19ToHg38.over.chain.gz.
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