text: user2862: When reading about allelic fraction (AF) and SNPs in cancer research, they always mention the fact that they're using heterozygous SNPs (informative SNPs). Why is this? Why can't we use homozygous SNPs?
  In this case, what is the reference base (from the reference genome)?
  
  user339: I'm not sure what I'm talking about, but I guess one could re-phrase Konrad's answer in terms of information theory. 
  The information content of a message (a packet of bits) is inversely proportional to the frequency of those bits. For example, if you randomly extract a word (the message) from an English book and the word is "the", you don't get much information about the book because "the" is very frequent and you see it everywhere. If, instead, the word happens to be the much rarer "bioinformatics" you start having a pretty good guess what the book is about.
  About SNPs, homozygote reference genotypes have very little information because most of the genomic positions in most of the people are homozygote reference. Heterozygote and homozygote non-reference are rarer and thus more informative. 
  So, I don't think there is anything wrong with using homozygote SNPs. They are ignored because they are so common that their information content is very small. 
  
  user29: I’m no longer working in tumour sequencing so I’m by no means an expert. But in a nutshell, the reason is that, as indicated, homozygous SNPs aren’t informative: if your allelic fraction is 100%, meaning you only observe a single nucleotide at a given position, we don’t know whether we’re dealing with a tumour related mutation. In fact, we probably don’t because the sample likely contains healthy as well as tumour cells.
  By contrast, tumour-specific variants always have an AF < 100%, in other words they exhibit some degree of heterozygosity.
  In fact, in healthy tissues you’d expect to see one of three cases: your variant allele (= sequence base ≠ reference) has a frequency of either 0% or 100% (homozygous), or 50% (heterozygous), ignoring rare somatic mutations. With tumour samples, by contrast, the fraction will vary depending on the penetrance of the variant in the tumour, and on the fraction of healthy to tumour cells in the sample.
  
original_text: 2862: <p>When reading about allelic fraction (AF) and SNPs in cancer research, they always mention the fact that they're using heterozygous SNPs (<em>informative</em> SNPs). Why is this? Why can't we use homozygous SNPs?</p>
  
  <p>In this case, what is the reference base (from the reference genome)?</p>
   339: <p>I'm not sure what I'm talking about, but I guess one could re-phrase Konrad's answer in terms of information theory. </p>
  
  <p>The information content of a message (a packet of bits) is inversely proportional to the frequency of those bits. For example, if you randomly extract a word (the message) from an English book and the word is "the", you don't get much information about the book because "the" is very frequent and you see it everywhere. If, instead, the word happens to be the much rarer "bioinformatics" you start having a pretty good guess what the book is about.</p>
  
  <p>About SNPs, homozygote reference genotypes have very little information because most of the genomic positions in most of the people are homozygote reference. Heterozygote and homozygote non-reference are rarer and thus more informative. </p>
  
  <p>So, I don't think there is anything wrong with using homozygote SNPs. They are ignored because they are so common that their information content is very small. </p>
   29: <p>I’m no longer working in tumour sequencing so I’m by no means an expert. But in a nutshell, the reason is that, as indicated, homozygous SNPs <em>aren’t informative</em>: if your allelic fraction is 100%, meaning you only observe a single nucleotide at a given position, we don’t know whether we’re dealing with a tumour related mutation. In fact, we probably don’t because the sample likely contains healthy as well as tumour cells.</p>
  
  <p>By contrast, tumour-specific variants always have an AF &lt; 100%, in other words they exhibit some degree of heterozygosity.</p>
  
  <p>In fact, in healthy tissues you’d expect to see one of three cases: your variant allele (= sequence base ≠ reference) has a frequency of either 0% or 100% (homozygous), or 50% (heterozygous), ignoring rare somatic mutations. With tumour samples, by contrast, the fraction will vary depending on the penetrance of the variant in the tumour, and on the fraction of healthy to tumour cells in the sample.</p>
  