text: user10056: According to GATK best practice, it is recommended that different VQSR models be built for SNPs and INDELs, because the annotations for high-quality SNPs and INDELs are systematically different (if I understand it correctly). Since annotations for good variants on autosomes could be different from those on X chromosome, e.g., DP for good variants on X chromosome could be substantially smaller than DP on autosomes due to having large number of male samples, it seems reasonable to build VQSR models separately for X chromosome and autosomes. However, no such advice is proposed on GATK website.
  My question is:
  Should we build VQSR models separately for autosomes and X chromosome? If yes, we will have 4 VQSR models: Auto SNPs, Auto INDELs, X SNPs and X INDELs.
  Cross-posting: https://www.biostars.org/p/9483110/
  
  user475: You are correct that differences in ploidy between autosomes (always ploidy=2) and X chromosome mean that the same VQSR model cannot be applied to both cases equally.
  However, this is the case only for male X chromosomes (in human species).
  Therefore, yes, I'd recommend building a separate VQSR model when it comes to male X chromosomes. Importantly, the processing has to be different not only at the VQSR step, but from the very beginning at the HaplotypeCaller step (if you are using GATK also for variant calling), which has to be used with the option ploidy = 1.
  So,
  On one hand -> Processing of autosomes (females and males) and x chromosomes (females only) can be done altogether with no differences all the way to VQSR (SNPs + INDELs as in best practices)
  On the other hand -> Processing of X chromosomes (only males) goes in separate, from variant calling to VQSR (SNPs + INDELs as in best practices)
  
original_text: 10056: <p>According to GATK best practice, it is recommended that different VQSR models be built for SNPs and INDELs, because the annotations for high-quality SNPs and INDELs are systematically different (if I understand it correctly). Since annotations for good variants on autosomes could be different from those on X chromosome, e.g., DP for good variants on X chromosome could be substantially smaller than DP on autosomes due to having large number of male samples, it seems reasonable to build VQSR models separately for X chromosome and autosomes. However, no such advice is proposed on GATK website.</p>
  <p><strong>My question is</strong>:</p>
  <p>Should we build VQSR models separately for autosomes and X chromosome? If yes, we will have 4 VQSR models: Auto SNPs, Auto INDELs, X SNPs and X INDELs.</p>
  <p>Cross-posting: <a href="https://www.biostars.org/p/9483110/" rel="nofollow noreferrer">https://www.biostars.org/p/9483110/</a></p>
   475: <p>You are correct that differences in ploidy between autosomes (always ploidy=2) and X chromosome mean that the same VQSR model cannot be applied to both cases equally.</p>
  <p>However, this is the case only for male X chromosomes (in human species).</p>
  <p>Therefore, yes, I'd recommend building a separate VQSR model when it comes to male X chromosomes. Importantly, the processing has to be different not only at the VQSR step, but from the very beginning at the HaplotypeCaller step (if you are using GATK also for variant calling), which has to be used with the option ploidy = 1.</p>
  <p>So,</p>
  <p>On one hand -&gt; Processing of autosomes (females and males) and x chromosomes (females only) can be done altogether with no differences all the way to VQSR (SNPs + INDELs as in best practices)</p>
  <p>On the other hand -&gt; Processing of X chromosomes (only males) goes in separate, from variant calling to VQSR (SNPs + INDELs as in best practices)</p>
  