4 ms·

Can downvoters provide some input? It seems contradictory article author is in front page, but at the same time author's comments are downvoted.

new299 6y ago
I recommend reading the previous thread to understand some of the issues: https://news.ycombinator.com/item?id=22830320 https://news.ycombinator.com/item?id=22830320 There are a number of issues with the approaches suggested by the author. In particular they’ve suggested an attenuated strain be spread by something similar to Pox Parties. Many might find these suggestions misguided and dangerous...
- danieltillett 6y ago
  I have not suggested that "pox party" spread would be a good idea, just that it would be hard to stop if a natural attenuated strain was found and that this would influence the way the regulatory agencies viewed its licensing. This is not really relevant to the idea of using an attenuated strain to accelerate the development of other vaccines. This would be done under controlled conditions where the attenuated strain would not spread.
lvs 6y ago
Yes, the input I'd provide is that the writer doesn't have a particularly good grasp of virology, but people in this community are upvoting as if this is authoritative. People who write authoritative blog posts without expertise right now should consider themselves part of the disinfo problem. I'll be concrete: the expected correlation between the cited deletions and pathogencity should be considered to approach zero. No evidence supports the hypothesis that single codon or single nucleotide deletions correlate with attenuation of strains. Furthermore, a basic understanding of molecular biology is all that's needed to dismiss the notion of a generalized correlation between observing deletions (or even insertions! or any general mutation!) and the pathologic outcome of infection with a virus. Biology doesn't support general claims of this nature. This is not a well-informed line of reasoning. Even the title of the post is wrong! These are not "gene deletions." These are single codon deletions or deletions of a few nucleotides. No genes have been deleted!!
- war1025 6y ago
  His "About me" page states: """ I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer. """ Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true. I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn." That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.
  - entee 6y ago
    At the risk of starting a flame war, lvs is mostly correct. These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids. The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context. Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article. The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here). However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter. In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect. 1.) https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....

new299 6y ago

I recommend reading the previous thread to understand some of the issues: https://news.ycombinator.com/item?id=22830320 https://news.ycombinator.com/item?id=22830320 There are a number of issues with the approaches suggested by the author. In particular they’ve suggested an attenuated strain be spread by something similar to Pox Parties. Many might find these suggestions misguided and dangerous...

danieltillett 6y ago
I have not suggested that "pox party" spread would be a good idea, just that it would be hard to stop if a natural attenuated strain was found and that this would influence the way the regulatory agencies viewed its licensing. This is not really relevant to the idea of using an attenuated strain to accelerate the development of other vaccines. This would be done under controlled conditions where the attenuated strain would not spread.

lvs 6y ago

Yes, the input I'd provide is that the writer doesn't have a particularly good grasp of virology, but people in this community are upvoting as if this is authoritative. People who write authoritative blog posts without expertise right now should consider themselves part of the disinfo problem. I'll be concrete: the expected correlation between the cited deletions and pathogencity should be considered to approach zero. No evidence supports the hypothesis that single codon or single nucleotide deletions correlate with attenuation of strains. Furthermore, a basic understanding of molecular biology is all that's needed to dismiss the notion of a generalized correlation between observing deletions (or even insertions! or any general mutation!) and the pathologic outcome of infection with a virus. Biology doesn't support general claims of this nature. This is not a well-informed line of reasoning. Even the title of the post is wrong! These are not "gene deletions." These are single codon deletions or deletions of a few nucleotides. No genes have been deleted!!

war1025 6y ago
His "About me" page states: """ I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer. """ Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true. I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn." That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.
- entee 6y ago
  At the risk of starting a flame war, lvs is mostly correct. These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids. The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context. Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article. The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here). However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter. In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect. 1.) https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....