4 ms·

I'm not following several different aspects of your comment here. First of all, the paper is in Nature, not Science. Second, the first and second paragraphs do

I'm not following several different aspects of your comment here. First of all, the paper is in Nature, not Science. Second, the first and second paragraphs do contain some relevant words, but nothing quantitative - literally the only quantitative number (not nomenclature number) in the entire first 2 paragraphs is CHIP being defined as >2% of something. Furthermore the reference to baseline genetic variation you mention is verbatim as follows: "Considering baseline genetic and extrinsic variability, the development of tools that permit the assessment of individual genetic susceptibility would improve risk stratification and long-term clinical management." And I would argue that the article (not paper) does _not_ convey the qualitative conclusion of elevated rates of nonstandard mutations, because it doesn't reference the baseline at all! It doesn't even present it as a comparison, like "We found MORE mutations in astronauts than would be expected of non-astronauts" - it literally just phrases it as "We found mutations in astronauts", which, considering that non-astronauts are exposed to radiation and get cancer + epigenetic mutations as well, doesn't differentiate it from the normal expected observation.

michaericalribo 4y ago
You’re eliding an entire body of research with “>2% of something.” That assertion is cited, and links to a full study. This is an observational study, and you may be analyzing it as a designed one. There was no randomization, no large scale matched control group per se—that wasn’t the intention. The intention is to analyze a specific population, and compare it to the existing literature on prevalence of mutations. That’s how these things are done, you have to use the citations given to understand the broader context of a study. One study is not useful on its own. Also, there’s this—they did hypothesis tests against a control group: > Variants (SNP/ InDel) generated with this method were compared with a normal dataset using Archer’s analysis pipeline to distinguish noise from a true call. The normal dataset was created with sequencing data from seven young, healthy individuals.
- whycombinetor 4y ago
  How am I eliding anything? My statement is that the only quantitative number in the first 2 paragraphs is the ">2%" figure. I'm also not criticizing the study, I'm criticizing the article and your defense of it. If "you have to use the citations given to understand the broader context of the study" - then if the point of a pop sci article is to effectively communicate the salience of the paper to lay audience, then that broader context needs to be communicated too.
michaericalribo 4y ago
No reasonable person reads “found genetic mutations in every astronaut” to plausibly mean “found bog standard genetic mutations everyone’s got.” This is pop science communication—journalism—not the actual scientific study. The goal isn’t scientific precision, it’s democratizing technical work
- whycombinetor 4y ago
  Really? I think everybody in the entire world knows somebody who's died from cancer, and the more educated of those people know that cancer is caused by genetic mutations. Also the theory of evolution is based on random genetic mutations - a very popular theory. I think a reasonable person would therefore know that everybody gets random genetic mutations over time. To put it concretely, if the chance of a random gene mutation is 10^-4 to 10^-6 per gene per generation, and there are 37 trillion cells in a human body, each cell containing about 20k genes, (all numbers from quick google searches) then the odds of having NO genetic mutations occur in your body in one day would be (forgive my back of the envelope math, assuming a generation is 20 years): (1 - 10^-6)**(37 trillion * 20000 / 365 / 20). My calculator can't keep enough precision to make this nonzero. i.e., everyone has genetic mutations constantly which makes the title of the article completely uninformative.
  - gus_massa 4y ago
    There are some tricks to reduce the number of important mutations. Germinal cells reproduce very slowly, so the eggs and sperm have fewer mutations. Also, cells inside the guts have some cascade method. The cells near the wall reproduce very seldom, but the intermediate cells reproduce faster, and the inner cells reproduce even faster. The inner cells that are reproducing fast die or get washed away, so the big number of possible mutations is removed. And the slow reproducing cells near the wall create more cells to replace the intermediate cells that replace the inner cells.
    - lanstin 4y ago
      Cool, that makes sense but I'd never seen it framed this way. (I knew about the slow rate for germ cells, but not gut.).

michaericalribo 4y ago

You’re eliding an entire body of research with “>2% of something.” That assertion is cited, and links to a full study. This is an observational study, and you may be analyzing it as a designed one. There was no randomization, no large scale matched control group per se—that wasn’t the intention. The intention is to analyze a specific population, and compare it to the existing literature on prevalence of mutations. That’s how these things are done, you have to use the citations given to understand the broader context of a study. One study is not useful on its own. Also, there’s this—they did hypothesis tests against a control group: > Variants (SNP/ InDel) generated with this method were compared with a normal dataset using Archer’s analysis pipeline to distinguish noise from a true call. The normal dataset was created with sequencing data from seven young, healthy individuals.

whycombinetor 4y ago
How am I eliding anything? My statement is that the only quantitative number in the first 2 paragraphs is the ">2%" figure. I'm also not criticizing the study, I'm criticizing the article and your defense of it. If "you have to use the citations given to understand the broader context of the study" - then if the point of a pop sci article is to effectively communicate the salience of the paper to lay audience, then that broader context needs to be communicated too.

michaericalribo 4y ago

No reasonable person reads “found genetic mutations in every astronaut” to plausibly mean “found bog standard genetic mutations everyone’s got.” This is pop science communication—journalism—not the actual scientific study. The goal isn’t scientific precision, it’s democratizing technical work

whycombinetor 4y ago
Really? I think everybody in the entire world knows somebody who's died from cancer, and the more educated of those people know that cancer is caused by genetic mutations. Also the theory of evolution is based on random genetic mutations - a very popular theory. I think a reasonable person would therefore know that everybody gets random genetic mutations over time. To put it concretely, if the chance of a random gene mutation is 10^-4 to 10^-6 per gene per generation, and there are 37 trillion cells in a human body, each cell containing about 20k genes, (all numbers from quick google searches) then the odds of having NO genetic mutations occur in your body in one day would be (forgive my back of the envelope math, assuming a generation is 20 years): (1 - 10^-6)**(37 trillion * 20000 / 365 / 20). My calculator can't keep enough precision to make this nonzero. i.e., everyone has genetic mutations constantly which makes the title of the article completely uninformative.
- gus_massa 4y ago
  There are some tricks to reduce the number of important mutations. Germinal cells reproduce very slowly, so the eggs and sperm have fewer mutations. Also, cells inside the guts have some cascade method. The cells near the wall reproduce very seldom, but the intermediate cells reproduce faster, and the inner cells reproduce even faster. The inner cells that are reproducing fast die or get washed away, so the big number of possible mutations is removed. And the slow reproducing cells near the wall create more cells to replace the intermediate cells that replace the inner cells.
  - lanstin 4y ago
    Cool, that makes sense but I'd never seen it framed this way. (I knew about the slow rate for germ cells, but not gut.).