Physical Phasing Information HaplotypeCaller


I am looking to use HaplotypeCaller to call germline variants, and I am particularly interested in the orientation of these variants relative to one another (cis- or trans-). There seems to be reference to physical phasing in the (HaplotypeCaller documentation)[], but I cannot find any physical phasing information in my VCF file.

For instance, I would expect the two variants below:

1 1647722 . G T 307.60 . AC=1;AF=0.500;AN=2;BaseQRankSum=-2.861;DP=29;ExcessHet=3.0103;FS=0.000;MLEAC=1;MLEAF=0.500;MQ=53.28;MQRankSum=-5.260;QD=10.61;ReadPosRankSum=-0.098;SOR=0.155 GT:AD:DP:GQ:PL 0/1:21,8:29:99:315,0,841
1 1647725 . G A 304.60 . AC=1;AF=0.500;AN=2;BaseQRankSum=-1.277;DP=29;ExcessHet=3.0103;FS=0.000;MLEAC=1;MLEAF=0.500;MQ=52.38;MQRankSum=-5.262;QD=10.50;ReadPosRankSum=-0.448;SOR=0.204 GT:AD:DP:GQ:PL 0/1:20,9:29:99:312,0,883

to be in the cis- orientation because they share nearly identical read counts, but I cannot find a corresponding annotation in the VCF file that says as much.

My command to call HaplotypeCaller is as below:

$gatk_launcher --java-options -Xmx${mem}g HaplotypeCaller \
-R $reference \
-I $bam_file \
-O $out_file \
-L $intervals_split &>> $log_file

Thank you for the help!!


  • bhanuGandhambhanuGandham Cambridge MAMember, Administrator, Broadie, Moderator admin
    edited April 19


    I checked with our dev team and this is what they had to say:

    Haplotypecaller and M2 automatically emit phased genotypes (i.e the PGT and PID tags and 0|1 instead of 0/1 genotypes) in any mode. However, the phasing algorithm is very conservative and a huge amount of phasing is not found.

    The way the phasing algorithm decides to phase is by checking whether two variants always occur on the same haplotype or always occur on a different haplotype. The excess haplotypes severely dilute the signal.

    This raises the question of whether we could do better, and the answer is yes, easily. The current code is very naive. The dev team is looking into making this process better.

    Post edited by bhanuGandham on
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