text: user16067: I have obtained several hundred raw, unassembled yeast genomes from NCBI and I am looking for advice on how to process the genomes for downstream analysis.
  I have a reference genome (S288C) to use for assembly/alignment but I'm not sure what to do first.
  So far I have run a quality assessment (FastQC) followed by trimming (Trimmomatic). But I'm not sure if I should align or assemble next. The problem with yeast is if I assemble to a reference genome it reduces the genome to a haplotype and could miss moments of heterozygosity present. And I'm not sure how it would work to do a de novo assembly as I'm assuming it's the same problem. Same with aligning to the reference genome.
  Are there ways to work around this? Does the yeast research community just ignore this issue? Are there tools currently out there that take all of this into account?
  
  user2108: What is your data type? Many assemblers can resolve heterozygosity.
  PacBio HiFi reads can be used with hifiasm to resolve both haplotypes rather trivially. This is the best case scenario and older sequencing projects are unlikely to have HiFi reads.
  If they are merely PacBio subreads, you can use Falcon-Unzip to get heterozygous regions (though this is now quite old and I am not sure that it is recommended anymore).
  For Illumina, the options are worse. Platanus is an assembler intended for the purpose of assembling heterozygous genomes. If nothing else, you can make the assembly and then just call variants.
  Note that many yeast are probably sequenced from a haploid strain.
  
original_text: 16067: <p>I have obtained several hundred raw, unassembled yeast genomes from NCBI and I am looking for advice on how to process the genomes for downstream analysis.</p>
  <p>I have a reference genome (<a href="http://sgd-archive.yeastgenome.org/sequence/S288C_reference/genome_releases/" rel="nofollow noreferrer">S288C</a>) to use for assembly/alignment but I'm not sure what to do first.</p>
  <p>So far I have run a quality assessment (FastQC) followed by trimming (Trimmomatic). But I'm not sure if I should align or assemble next. The problem with yeast is if I assemble to a reference genome it reduces the genome to a haplotype and could miss moments of heterozygosity present. And I'm not sure how it would work to do a de novo assembly as I'm assuming it's the same problem. Same with aligning to the reference genome.</p>
  <p>Are there ways to work around this? Does the yeast research community just ignore this issue? Are there tools currently out there that take all of this into account?</p>
   2108: <p>What is your data type? Many assemblers can resolve heterozygosity.</p>
  <p>PacBio HiFi reads can be used with <a href="https://github.com/chhylp123/hifiasm" rel="nofollow noreferrer">hifiasm</a> to resolve both haplotypes rather trivially. This is the best case scenario and older sequencing projects are unlikely to have HiFi reads.</p>
  <p>If they are merely PacBio subreads, you can use <a href="https://pb-falcon.readthedocs.io/en/latest/about.html." rel="nofollow noreferrer">Falcon-Unzip</a> to get heterozygous regions (though this is now quite old and I am not sure that it is recommended anymore).</p>
  <p>For Illumina, the options are worse. <a href="http://platanus.bio.titech.ac.jp/" rel="nofollow noreferrer">Platanus</a> is an assembler intended for the purpose of assembling heterozygous genomes. If nothing else, you can make the assembly and then just call variants.</p>
  <p><strong>Note that many yeast are probably sequenced from a haploid strain.</strong></p>
  