So I also didn't include that the apparent relationship to MSH3 and this mysterious sequence was based on amino acid sequence homology, and not the nucleotide sequence. This itself also causes a lot of issues since many (MANY) amino acid sequences will be similar across many species. You can do a BLAST search of the 6 amino acids to find similarities. This also seems improper since you would only include 6 amino acids and leave 1 nucleotide absent, unless the researchers went further and included MORE than the 6 amino acids coded by the 19 (18 actually) nucleotide sequence, and at that time it's really a circular search.
Modern Discontent, I absolutely love your article, even though, admittedly, some paragraphs were above my head.
The sequence in question is indeed short. It is also extremely deserving to be where it is in Sars-Cov-2, where it leads to furin cleavage, infectivity, and pandemic potential.
It is, perhaps not "natural", but perfectly appropriate for a sophisticated researcher to add that sequence to Sars-Cov-2 for a specific purpose (infectivity and pathogenicity).
Apologies if it was confusing. I think the best approach is to follow the logic of the researchers.
Starting from the weird 12-nucleotide sequence that the researchers were right to question they tried doing a BLAST search and somehow came upon the Moderna patent, which is weird because that sequence was too short to come up with any viable sequence, let a lone in the patent database which wouldn't be the first place I check.
This leads me to think that either they randomly guessed, in which case they extended the nucleotide sequence past the 12 using the spike's sequence- but that would go against their original argument of using only the 12-nucleotides. Or, they possibly found out about this sequence being in the Moderna patent and came up with a reason to tie the two together (I can't confirm this argument).
One big issue is that they saw the sequence went past the 12 original nucleotides and pushed it all the way to 19. The question then is if the entire 19 sequence is relevant, or if 7 of the nucleotides are erroneous, which is my argument. At that point you're making an argument based on a sequence that would already be in the original SARS virus via the 7 erroneous nucleotides. So does that mean that there was a removal of 7 nucleotides to make room for the 12 insertions PLUS an additional 7 to get to the 19 nucleotides, and somehow those additional 7 happen to code for the same amino acids as the original SARS and SARS-COV2?
So that's why I think the researchers overextended the sequence in question and it led them to a wrong conclusion to assume some relationship to MSH3. The entire 19 sequence may be from the patent, but is it that the entire 19 sequence ended up in the spike, or is it that the 12-nucleotide insertion ended up in the spike and that addition happened to lead to the 19-nucleotide sequence.
Now, there is a question where those 12-nucleotides came from, but like I said that sequence is so small that it really could come from anywhere. The authors of the recent article you included in your post suggest a relationship to ENaC-a which has its own furin cleavage site that matches the RRAR'SVAS amino acid sequence seen in the spike, but that article doesn't explain the presence of the proline (P) residue so where would that have come from?
Overall, the CGG sequence raises suspicions as to the origins of that sequence, but for me that origin is not related to the Moderna patent, and the study may be leading people down a wrong conclusion.
What has been called the Keep It Simple Stupid method ( KISS), used to be called Occam’s Razor, and the philosophy inherent therein seems very nearly unassailable. QED.
Yes, that's an apt term Morton. I definitely would argue that the paper went too deep and ended up in the wrong spot evidence-wise. As to how they reached that conclusion is another question. Like I stated the information presented by then doesn't actual reach their end point of the patent. I am open to me just not BLAST-ing my way to their result properly, but trying to walk through their process I just couldn't get to their result.
Well quite honestly for us there is no elegant answer. But that also doesn't mean that we should assume all ideas provided are plausible as well. I think there are many other papers out there that may hypothesize that gets closer to the idea, but this one personally isn't it. Like I stated, I'm not sure but they needed a little more help than just "let's check this 12-base sequence" and happen to just come across this Moderna patent, then work retroactively to somehow associate the two.
Exactly, why is it in the Moderna patent? Was it a case of magic ,or Devine providence, or... look for the probably simplest explanation, i.e.,human intervention for a desired end.
Well my argument is that some engineering may have occurred to lead to that insertion, but that incident may have happened independent of the Moderna patent. It's only through coincidence that the sequences align. As to how it got there, I'm not sure, I don't know much in the way of engineering but I'm wondering if they have the capabilities of splicing and inserting this sequence without the need for serial passage.
So I also didn't include that the apparent relationship to MSH3 and this mysterious sequence was based on amino acid sequence homology, and not the nucleotide sequence. This itself also causes a lot of issues since many (MANY) amino acid sequences will be similar across many species. You can do a BLAST search of the 6 amino acids to find similarities. This also seems improper since you would only include 6 amino acids and leave 1 nucleotide absent, unless the researchers went further and included MORE than the 6 amino acids coded by the 19 (18 actually) nucleotide sequence, and at that time it's really a circular search.
Modern Discontent, I absolutely love your article, even though, admittedly, some paragraphs were above my head.
The sequence in question is indeed short. It is also extremely deserving to be where it is in Sars-Cov-2, where it leads to furin cleavage, infectivity, and pandemic potential.
It is, perhaps not "natural", but perfectly appropriate for a sophisticated researcher to add that sequence to Sars-Cov-2 for a specific purpose (infectivity and pathogenicity).
But why is it in the Moderna MSH3 patent?
Apologies if it was confusing. I think the best approach is to follow the logic of the researchers.
Starting from the weird 12-nucleotide sequence that the researchers were right to question they tried doing a BLAST search and somehow came upon the Moderna patent, which is weird because that sequence was too short to come up with any viable sequence, let a lone in the patent database which wouldn't be the first place I check.
This leads me to think that either they randomly guessed, in which case they extended the nucleotide sequence past the 12 using the spike's sequence- but that would go against their original argument of using only the 12-nucleotides. Or, they possibly found out about this sequence being in the Moderna patent and came up with a reason to tie the two together (I can't confirm this argument).
One big issue is that they saw the sequence went past the 12 original nucleotides and pushed it all the way to 19. The question then is if the entire 19 sequence is relevant, or if 7 of the nucleotides are erroneous, which is my argument. At that point you're making an argument based on a sequence that would already be in the original SARS virus via the 7 erroneous nucleotides. So does that mean that there was a removal of 7 nucleotides to make room for the 12 insertions PLUS an additional 7 to get to the 19 nucleotides, and somehow those additional 7 happen to code for the same amino acids as the original SARS and SARS-COV2?
So that's why I think the researchers overextended the sequence in question and it led them to a wrong conclusion to assume some relationship to MSH3. The entire 19 sequence may be from the patent, but is it that the entire 19 sequence ended up in the spike, or is it that the 12-nucleotide insertion ended up in the spike and that addition happened to lead to the 19-nucleotide sequence.
Now, there is a question where those 12-nucleotides came from, but like I said that sequence is so small that it really could come from anywhere. The authors of the recent article you included in your post suggest a relationship to ENaC-a which has its own furin cleavage site that matches the RRAR'SVAS amino acid sequence seen in the spike, but that article doesn't explain the presence of the proline (P) residue so where would that have come from?
Overall, the CGG sequence raises suspicions as to the origins of that sequence, but for me that origin is not related to the Moderna patent, and the study may be leading people down a wrong conclusion.
What has been called the Keep It Simple Stupid method ( KISS), used to be called Occam’s Razor, and the philosophy inherent therein seems very nearly unassailable. QED.
Yes, that's an apt term Morton. I definitely would argue that the paper went too deep and ended up in the wrong spot evidence-wise. As to how they reached that conclusion is another question. Like I stated the information presented by then doesn't actual reach their end point of the patent. I am open to me just not BLAST-ing my way to their result properly, but trying to walk through their process I just couldn't get to their result.
So, what's the elegant answer? Everyone is looking for the smoking gun.
Well quite honestly for us there is no elegant answer. But that also doesn't mean that we should assume all ideas provided are plausible as well. I think there are many other papers out there that may hypothesize that gets closer to the idea, but this one personally isn't it. Like I stated, I'm not sure but they needed a little more help than just "let's check this 12-base sequence" and happen to just come across this Moderna patent, then work retroactively to somehow associate the two.
Exactly, why is it in the Moderna patent? Was it a case of magic ,or Devine providence, or... look for the probably simplest explanation, i.e.,human intervention for a desired end.
Well my argument is that some engineering may have occurred to lead to that insertion, but that incident may have happened independent of the Moderna patent. It's only through coincidence that the sequences align. As to how it got there, I'm not sure, I don't know much in the way of engineering but I'm wondering if they have the capabilities of splicing and inserting this sequence without the need for serial passage.
Possibly not.