text: user4806: Is there a methodology for detecting whether a genome has been tampered with by a biologist?  For instance, say there has been an ebola outbreak such as in "The Andromeda Strain".  Is there a way a researcher can tell by just looking at the ebola genetic data and determine it is a genetically engineered strain?
  Some ideas I have:
  
  organism is abnormally close to unrelated organisms, i.e. some of the genetic code from the other organisms has been inserted into the first
  subsequences are very different from the rest of the genome.  If there is a consistent rate of mutation applied to the entire genome, then a subsequence that is abnormally noise free could be inserted.
  combination of 1 and 2: finding clear instances of unrelated organism genomes inserted into the genome being examined.
  
  Additionally, are there any publicly accessible reference genomes that are known to be genetically engineered, that I could use as examples to test such ideas?
  UPDATE: the wikipedia article on detecting genetically modified organism is not quite what I am looking for, since it claims current methods cannot detect unknown genetic modification.
  https://en.wikipedia.org/wiki/Detection_of_genetically_modified_organisms
  
  Currently, it is highly unlikely that the presence of unexpected or
    even unknown GMOs will be detected, since either the DNA sequence of
    the transgene or its product, the protein, must be known for
    detection.
  
  
  user3848: The definition of a GMO for example UK GMO regulatory bodies (HSE) is strictly the artificial introduction of foreign genetic material using targeted genetic engineering, such as splicing,  genome integration etc... Attenuation for example by serial passage the basis of the yellow fever vaccine, does not count as a GMO. 
  The simple answer is look at phylogenetic trees between the GMO strain against the total distribution of isolates. If large regions have been spliced the 'silent mutation rate' looks very different,.because the GMO parent is from a very different environment to the recipient.  The switch in replication rate affects the numbers of 'silent mutation', which is fast in RNA viruses.
  If the GMO is a point mutation, ie limited amino acid change then I've actually done this with dengue virus and it is fairly easy because the novel mutation make the GMO 'stick out'.of the phylogeny against all natural mutation patterns. At this point the outlier is tracked back to Genbank where the relavant publication defines the engineered virus.
  If you are inferring a conspiracy theory that is a different process and a different discussion, particularly if it is Ebolavirus which is a Category 4 pathogen. The investigation is again within the phylogeny, but in this case the answer is always the isolate is a natural zoonose from a sylvatic (wild) transmission cycle which has spilled over into humans.
  
original_text: 4806: <p>Is there a methodology for detecting whether a genome has been tampered with by a biologist?  For instance, say there has been an ebola outbreak such as in "The Andromeda Strain".  Is there a way a researcher can tell by just looking at the ebola genetic data and determine it is a genetically engineered strain?</p>
  
  <p>Some ideas I have:</p>
  
  <ol>
  <li><p>organism is abnormally close to unrelated organisms, i.e. some of the genetic code from the other organisms has been inserted into the first</p></li>
  <li><p>subsequences are very different from the rest of the genome.  If there is a consistent rate of mutation applied to the entire genome, then a subsequence that is abnormally noise free could be inserted.</p></li>
  <li><p>combination of 1 and 2: finding clear instances of unrelated organism genomes inserted into the genome being examined.</p></li>
  </ol>
  
  <p>Additionally, are there any publicly accessible reference genomes that are known to be genetically engineered, that I could use as examples to test such ideas?</p>
  
  <p>UPDATE: the wikipedia article on detecting genetically modified organism is not quite what I am looking for, since it claims current methods cannot detect unknown genetic modification.</p>
  
  <p><a href="https://en.wikipedia.org/wiki/Detection_of_genetically_modified_organisms" rel="nofollow noreferrer">https://en.wikipedia.org/wiki/Detection_of_genetically_modified_organisms</a></p>
  
  <blockquote>
    <p>Currently, it is highly unlikely that the presence of unexpected or
    even unknown GMOs will be detected, since either the DNA sequence of
    the transgene or its product, the protein, must be known for
    detection.</p>
  </blockquote>
   3848: <p>The definition of a GMO for example UK GMO regulatory bodies (HSE) is strictly the artificial introduction of foreign genetic material using targeted genetic engineering, such as splicing,  genome integration etc... Attenuation for example by serial passage the basis of the yellow fever vaccine, does not count as a GMO. </p>
  
  <p>The simple answer is look at phylogenetic trees between the GMO strain against the total distribution of isolates. If large regions have been spliced the 'silent mutation rate' looks very different,.because the GMO parent is from a very different environment to the recipient.  The switch in replication rate affects the numbers of 'silent mutation', which is fast in RNA viruses.</p>
  
  <p>If the GMO is a point mutation, ie limited amino acid change then I've actually done this with dengue virus and it is fairly easy because the novel mutation make the GMO 'stick out'.of the phylogeny against all natural mutation patterns. At this point the outlier is tracked back to Genbank where the relavant publication defines the engineered virus.</p>
  
  <p>If you are inferring a conspiracy theory that is a different process and a different discussion, particularly if it is Ebolavirus which is a Category 4 pathogen. The investigation is again within the phylogeny, but in this case the answer is always the isolate is a natural zoonose from a sylvatic (wild) transmission cycle which has spilled over into humans.</p>
  