<p>As the two alleles in a genotype are separated by <code>/</code> but not <code>|</code>, the main v4.2.1 VCF is not phased. The <a href="https://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/release/AshkenazimTrio/HG002_NA24385_son/NISTv4.2.1/README_v4.2.1.txt" rel="nofollow noreferrer">README</a> says the phased VCFs are available in the <a href="https://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/release/AshkenazimTrio/HG002_NA24385_son/NISTv4.2.1/GRCh38/SupplementaryFiles/" rel="nofollow noreferrer">SupplementaryFiles</a> directory. It contains a few versions of VCFs with v4.2.1 genotype calls but with phasing from additional tools such as whatshap and hifiasm. I don't know which version is the most accurate, though.</p>

CC BY-SA 4.0
2022-05-30T14:15:31.680Z
Thanks, I was aware of the convention that `/` means unphased and `|` means phased, but the fact that it labeled some variants as `1/0` really threw me off. Not sure why they'd do that.
TimD1
CC BY-SA 4.0
2022-05-30T14:18:22.980Z
I had interpreted the README to mean that they included the trio hifiasm dipcall VCFs in the `SupplementaryFiles` directory, not the resulting phased reference benchmark. Thanks!
TimD1
CC BY-SA 4.0
2022-05-31T19:27:13.937Z
@TimD1 I asked a question about that recently and got an interesting possible reason, but I haven't had the time to look more closely. Here it is, in case you find it interesting: [Why does GATK produce both 0/1 and 1/0 genotypes in the same file? Are the two not equivalent?](https://bioinformatics.stackexchange.com/q/18762)
terdon
CC BY-SA 4.0
2022-05-30T00:44:20.463Z
2022-05-30T20:10:55.260Z
2022-05-30T20:10:55.260Z
user172818
<p>Specifically, the NISTv4.2.1 HG002 dataset <a href="https://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/release/AshkenazimTrio/HG002_NA24385_son/" rel="nofollow noreferrer">here</a> (<a href="https://www.nist.gov/programs-projects/genome-bottle" rel="nofollow noreferrer">more info on Genome in a Bottle</a>). According to their README, the HG002 v4.2.1 VCF should be fully phased.</p>
<blockquote>
<p>For HG001, HG002, and HG005, we have phased the v4.2.1 benchmark vcfs by transferring phasing information from a phased assembly-based trio-hifiasm dipcall vcf to the v4.2.1 vcf</p>
</blockquote>
<p>I ask because there appear to be FAR more heterozygous variants on the second haplotype than the first (<code>0|1</code> &gt;&gt; <code>1|0</code>).</p>
<p>For example:</p>
<pre><code>tail -n 500000 HG002_GRCh38_1_22_v4.2.1_benchmark.vcf | \
        cut -f 10 | cut -f1 -d: | sort | uniq -c
 302960 0/1
   1104 1/0
 190042 1/1
   2037 1/2
   3857 2/1
</code></pre>
<p>Is this simply an artifact of how these truth sets were produced? For example, if the GRCh38 (haploid) FASTA was meant to be haplotype 1, then it makes sense that it's nearly identical to HG002's haplotype 1, and haplotype 2 has more differences. Is that the case, or are only certain variants phased (such as those that pass a minimum confidence threshold, or are in a high-quality BED region)?</p>

<vcf><phasing>
Are the GIAB reference genomes (HG00N) fully phased?
# Are the GIAB reference genomes (HG00N) fully phased?

(Asked by: username_0 on 2022-05-29)

Specifically, the NISTv4.2.1 HG002 dataset here (more info on Genome in a Bottle). According to their README, the HG002 v4.2.1 VCF should be fully phased.

For HG001, HG002, and HG005, we have phased the v4.2.1 benchmark vcfs by transferring phasing information from a phased assembly-based trio-hifiasm dipcall vcf to the v4.2.1 vcf

I ask because there appear to be FAR more heterozygous variants on the second haplotype than the first (0|1 >> 1|0).
For example:
tail -n 500000 HG002_GRCh38_1_22_v4.2.1_benchmark.vcf | \
        cut -f 10 | cut -f1 -d: | sort | uniq -c
 302960 0/1
   1104 1/0
 190042 1/1
   2037 1/2
   3857 2/1

Is this simply an artifact of how these truth sets were produced? For example, if the GRCh38 (haploid) FASTA was meant to be haplotype 1, then it makes sense that it's nearly identical to HG002's haplotype 1, and haplotype 2 has more differences. Is that the case, or are only certain variants phased (such as those that pass a minimum confidence threshold, or are in a high-quality BED region)?

**Tags:** vcf, phasing

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## 1 answers

### Answer by username_1 on 2022-05-30. Score: 2 | Accepted answer

As the two alleles in a genotype are separated by `/` but not `|`, the main v4.2.1 VCF is not phased. The [README](https://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/release/AshkenazimTrio/HG002_NA24385_son/NISTv4.2.1/README_v4.2.1.txt) says the phased VCFs are available in the [SupplementaryFiles](https://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/release/AshkenazimTrio/HG002_NA24385_son/NISTv4.2.1/GRCh38/SupplementaryFiles/) directory. It contains a few versions of VCFs with v4.2.1 genotype calls but with phasing from additional tools such as whatshap and hifiasm. I don't know which version is the most accurate, though.

> **Comments:**
> **username_0**: Thanks, I was aware of the convention that `/` means unphased and `|` means phased, but the fact that it labeled some variants as `1/0` really threw me off. Not sure why they'd do that.  
> **username_0**: I had interpreted the README to mean that they included the trio hifiasm dipcall VCFs in the `SupplementaryFiles` directory, not the resulting phased reference benchmark. Thanks!  
> **username_2**: @TimD1 I asked a question about that recently and got an interesting possible reason, but I haven't had the time to look more closely. Here it is, in case you find it interesting: [Why does GATK produce both 0/1 and 1/0 genotypes in the same file? Are the two not equivalent?](https://bioinformatics.stackexchange.com/q/18762)  

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