text: user15648: I have done a DGE recently and have been looking at the DGE list. One of the genes is HLA-A. However, when I dug deeper I realised there are hundreds of HLA-A genes with unique ENSEMBL number (of course it's HLA...). A few other HLA-A genes also show up on the table but are not significant at all.
  Considering the way Salmon deals with multimapping reads, can I assume these expressing genes are different enough that they shouldn't be consider the same? Or should the expression of all HLA-A genes considered as one single gene for the purpose of identifying differentially expressed genes?
  I do understand that this may be more of a biological question than bioinformatics, but I also want to see if it is a practice pouring the HLA genes (or other variable genes/loci of similar nature) with different sequences together when doing DGE, and whether the statistics would be valid if I do so?
  
  user37: You need specialized tools to study HLA genes. Generic tools won't work well. Before other analysis, you should get the correct genotype first. Try arcasHLA. It has been a popular HLA genotyper for RNA-seq data. When you know the genotype, I guess you may get rid of other HLA-A alleles and redo the differential analysis if you are interested in HLA-A. I haven't done this, though. Just a thought.
  
original_text: 15648: <p>I have done a DGE recently and have been looking at the DGE list. One of the genes is HLA-A. However, when I dug deeper I realised there are hundreds of HLA-A genes with unique ENSEMBL number (of course it's HLA...). A few other HLA-A genes also show up on the table but are not significant at all.</p>
  <p>Considering the way Salmon deals with multimapping reads, can I assume these expressing genes are different enough that they shouldn't be consider the same? Or should the expression of all HLA-A genes considered as one single gene for the purpose of identifying differentially expressed genes?</p>
  <p>I do understand that this may be more of a biological question than bioinformatics, but I also want to see if it is a practice pouring the HLA genes (or other variable genes/loci of similar nature) with different sequences together when doing DGE, and whether the statistics would be valid if I do so?</p>
   37: <p>You need specialized tools to study HLA genes. Generic tools won't work well. Before other analysis, you should get the correct genotype first. Try <a href="https://academic.oup.com/bioinformatics/article/36/1/33/5512361" rel="nofollow noreferrer">arcasHLA</a>. It has been a popular HLA genotyper for RNA-seq data. When you know the genotype, I guess you may get rid of other HLA-A alleles and redo the differential analysis if you are interested in HLA-A. I haven't done this, though. Just a thought.</p>
  