19 ms·

Supercomputer analysis of Covid-19 leads to new theory

469 points by mvgoogler 6y ago

dekhn 6y ago
I can't really see why you would need a supercomputer to do the analysis they did (it shows SC centers are getting desperate for users; I wouldn't even have been allowed to run this code on a supercomputer when I was an academic, because it didn't need interconnect for strong scaling.
- secondcoming 6y ago
  Maybe to test the algorithms and results, so that next time something like this happens there can be a list of suggested treatments ready far sooner.
  - dekhn 6y ago
    The issue is that, from what I can tell, the authors just used R to analyze some data, with no explicit parallelism. You would do a better job just renting time on AWS, saving money for everybody.
    - mnw21cam 6y ago
      Depends how much of the "supercomputer" the calculation used. If it reserved a single CPU core on a single node, then that'd be cheap, allowing the rest of the system to get on with something else. There's no reason AWS would be cheaper.
      - natechols 6y ago
        The supercomputer in this article is extremely specialized hardware design to maximize peak performance across all nodes. Using just a single CPU core to run a bioinformatics study would be like taking an army tank to drop the kids off at soccer practice.
      - dekhn 6y ago
        The supercomputer nodes cost far more, per node, than AWS machines- 15% or more of the budget was spent on interconnect. SUpercomputers don't partition CPUs like that, because interference causes small performance degradation. Unfortunately, CPU is not perfectly compressible- in particular, the cache is shared by all processes that run on the CPU, so if you run another job on the same node, you will see slower performance due to higher cache replacement (this is measured using Cycles Per Instruction).
    - btilly 6y ago
      R handles statistics. It does not simulate complex biochemical interactions in different parts of the body. From the description, they did something that requires a lot more horsepower.
      - dekhn 6y ago
        I read the underlying article (https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177) and was unable to find any evidence of that. In fact the paper doesn't mention anything about SUmmit or details on the computations :( There certainly wasn't any "heavy biochemical calculations"; this work is entirely comparative genomics, so just operating on DNA strings. I see this fluff article https://www.ornl.gov/blog/genomics-code-exceeds-exaops-summit-supercomputer https://www.ornl.gov/blog/genomics-code-exceeds-exaops-summi... and there may be more detail here: https://www.hpcuserforum.com/presentations/april2019/JoubertORNL.pdf https://www.hpcuserforum.com/presentations/april2019/Joubert... which shows near-linear performance they ascribe to "Made possible by aggressive communication overlap and low-congestion Mellanox Infiniband fat tree network with adaptive routing" So there may actually be an HPC/supercomputer story in there, but I'm having trouble figuring out what they did in this most recent work.
        rrss 6y ago
        I can't find details either, but I think they just used R for the post-processing, and there's a lot of computation behind this sentence: > RNA-Seq analysis was performed using the latest version of the human transcriptome I found this article discussing read mapping for RNA sequence analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833417/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833417/ > In particular, RNA sequencing (RNA-seq) technology,1 which provides a comprehensive profile of a transcriptome, is increasingly replacing conventional expression microarrays.2 Primary data processing in RNA-seq (as well as in other massive sequencing experiments, including genome resequencing) involves mapping reads onto a reference genome. This step constitutes a computationally expensive process in which, in addition, sensitivity is a serious concern
        6y ago
    - secabeen 6y ago
      In my experience with research computing, if you are able to keep a computer doing active work more than 60% of the time, it will be cheaper to purchase and run that computer yourself than renting it from AWS. That's the case even with commodity machines with only 10G Ethernet interconnect. $15k for a machine is only $0.34/hour over 5 years. That doesn't buy much of an AWS machine. (Yes, cooling, real estate and power are all overhead on that, but researchers often don't pay those costs directly, they are covered by the university with other monies.)
      - dekhn 6y ago
        You're completely ignoring the other valuable aspects of being in a cloud: you're close to huge amounts of high throughput storage (blob and DB), and can increase/decrease the size of your fleet trivially. These are critical to nearly all modern scientific workflows (moreso than the raw compute, IMHO). As for the cost structure for research computing, the argument that the costs are externalized isn't a good one- that overhead that pays for the facility, and the networking, comes out of your grant money, and using grad student time to admin your cluster often just causes your grad students to leave for FAAMG.
        secabeen 6y ago
        > You're completely ignoring the other valuable aspects of being in a cloud: you're close to huge amounts of high throughput storage (blob and DB), and can increase/decrease the size of your fleet trivially. These are critical to nearly all modern scientific workflows (moreso than the raw compute, IMHO). That has not been my experience. There are lots of scientific workflows that only need 10s of TB at most, yet can still consume lots of cycles. > As for the cost structure for research computing, the argument that the costs are externalized isn't a good one- that overhead that pays for the facility, and the networking, comes out of your grant money, and using grad student time to admin your cluster often just causes your grad students to leave for FAAMG. At the universities I've worked at, equipment (large purchases) is except from overhead, or results in a lower overhead charge. (Researchers balk at paying a ~50% overhead rate on a $1million instrument). Using grad student time to admin your cluster is dumb, but I'm more talking about users who need single-digit numbers of computers. If you need real HPC, you're in the world of queues, national and regional supercomputers, etc. etc.
- searine 6y ago
  >I can't really see why you would need a supercomputer to do the analysis they did The article is fluff. 98% of all bioinformatics is done on "supercomputers" or 'high performance computing environments" saying the researchers used supercomputers to analyze the expression data is like saying someone used a shovel to dig a hole.
  - vardump 6y ago
    Don't we all have supercomputers in our pockets?
    - dekhn 6y ago
      No. Although our phones are extraordinary, they are not supercomputers. Supercomputers, more or less by legacy historical defintions, are collections of computing resources connected by a fast network with the goal of scaling to solve problems that could not be solved with conventional systems. Phones aren't really designed to solve that kind of problem. That said, many problems that previously would have required a supercomputer, can now be solved on phones.
      - vardump 6y ago
        I think my sarcasm tag had some kind of issue and it wasn't visible.
  - tzs 6y ago
    The article doesn't simply say they used a supercomputer. It says they used Oak Ridge's Summit supercomputer, the second fastest in the world. Unless 98% of all bioinformatics done on a top 2 supercomputer, your point fails.
    - searine 6y ago
      >It says they used Oak Ridge's Summit supercomputer, the second fastest in the world. The shovel had racing stripes. Got it. The job doesn't change based on what hardware it is run on.
- dooglius 6y ago
  Or that COVID is getting priority over anything else and there were no COVID analyses that used the interconnect better
- natechols 6y ago
  I was wondering about this too - when I saw the title I assumed it was a molecular dynamics study.
klysm 6y ago
The anthropomorphization of computers (especially powerful ones) is pretty annoying. A _person used a supercomputer_ to analyze Covid-19, and I’m guessing the theory didn’t just ‘emerge’ from the computer.
- itisit 6y ago
  Behold the oracle!
- traceroute66 6y ago
  "I'm sorry Dave. I'm afraid I can't do that."
  - avmich 6y ago
    Computers better be familiar with that story and with what happens next.
    - jasonjayr 6y ago
      "Daisy, Daisy ....."
    - marcosdumay 6y ago
      Future computers will probably be smart enough to not disobey any human until it can release the hypno-drones all at the same time.
- nr2x 6y ago
  Likewise while a computer can produce data quite well, theories are still a purely human domain.
  - Jtsummers 6y ago
    > theories are still a purely human domain. Why do you believe that? Theories are attempts to explain the mechanism of something based on the observed data. Given data on patient symptoms and known drugs (ACE inhibitors in this case) and their effects, a computer could easily produce a theory that the disease acted like ACE inhibitors. It'd still take a human to write the program to generate these theories, but a computer could do it.
debacle 6y ago
The study itself: https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177 Excerpts from the abstract: Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2. ... This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. https://en.wikipedia.org/wiki/Bradykinin https://en.wikipedia.org/wiki/Bradykinin
secondcoming 6y ago
Interesting, it seems to explain most aspects of the virus infection, except for the scenario where a carrier exhibits little or no symptoms
- jfoster 6y ago
  Could that be determined by something like the level of Vitamin D a person has?
gchokov 6y ago
Vitamin D for the win!
- hosh 6y ago
  We don’t know the dosage or protocol for stopping the bradykinin storm, or even if this hypothesis is confirmed through more tests ... but it seems sensible to me to make sure one has a healthy level of Vitamin D, and that is actionable for a lot of people.
  - throwaway43234 6y ago
    > that is actionable for a lot of people Really hoping this is better by the next few months or my Seattle winter will be even more pill popping to maintain basic human functionality....
    - hinkley 6y ago
      I recommend a bottle of chewables, placed somewhere you're likely to see it every day. It's makes it easier to get others to take their dose as well, if you take the water glass out of the equation.
    - hosh 6y ago
      If you cook or grow your own food (microgreens, mushroom in a kitchen cabinet), there are alternatives. For example: https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-place-your-shiitake-mushrooms-in-sunlight/ https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-pla... This works for both shiitake and button (portobello) mushrooms. This trick came from Paul Stamets, one of the world’s foremost mycologist. He is based out in Casscadia. You may have to track down exactly what “2 days” means... I wouldn’t be surprised if he went looking for a way to maintain his Vitamin D health. You only need 10g of this four times a week, according to this article. While it is summer time in Seattle, you can prepare a bunch and then dry them, so they last until next spring.
      - gchokov 6y ago
robomartin 6y ago
Am I the only one bothered by the use of “theory” when this is a hypothesis and, in particular, the back and forth flipping between the two terms in the article?
- TheSpiceIsLife 6y ago
  Probably just you ;) Lay people use the two interchangeably. In at least two of the thesaurus I have at hand hypothesis is synonymous is theory.
  - andrewflnr 6y ago
    It seems to me like even scientists use the terms not quite interchangeably, but on a spectrum. String theory is still "theoretical physics", not "hypothetical physics", even though it will likely never be tested in our lifetime.
    - zuminator 6y ago
      That's because the whole internet idea of "a theory is a well-tested hypothesis" is silly and wrong. A hypothesis is a specific supposition or question about the way things work which if true has some level of explanatory power in a field of study. It can be confirmed or unconfirmed. It's still a hypothesis. An answered question is still a question. A theory is a explanatory framework for a body of knowledge. Unlike a hypothesis, it's not inherently a question or a guess. That doesn't mean it's "true." It also can be unconfirmed (as you say, string theory) or even demonstrably false (phlogiston theory, Ptolemaic theory) and still be a theory. Obviously there's considerable overlap between the two concepts and as you say they are sometimes used almost interchangeably. Colloquially, "I'm testing my hypothesis that orally ingesting booze provides protection against infection, which if confirmed will be a key part of a theory of booze immunology" gets collapsed into "I'm testing my theory of booze immunology." Big deal. It really only matters because people let themselves get bent out of shape about the whole "evolution is just a theory" thing. And since I'm ranting already, evolution isn't "just a theory" because evolution itself isn't a "theory," evolution is the natural phenomenon that is being theorized about.
hellofunk 6y ago
> Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19. The vitamin is readily available over the counter, and around 20% of the population is deficient. If indeed the vitamin proves effective at reducing the severity of bradykinin storms, it could be an easy, relatively safe way to reduce the severity of the virus.
- nradov 6y ago
  See Dr. Gerry Schwalfenberg's letter on the "Vitamin D hammer" for treating respiratory viruses. While not a controlled study it does point toward an avenue for further research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890/
- shubhamjain 6y ago
  This Medium article was written on March 10 [1]. "Put simply, medics found that severely ill flu patients nursed outdoors recovered better than those treated indoors. A combination of fresh air and sunlight seems to have prevented deaths among patients; and infections among medical staff.[1] There is scientific support for this. Research shows that outdoor air is a natural disinfectant. Fresh air can kill the flu virus and other harmful germs. Equally, sunlight is germicidal and there is now evidence it can kill the flu virus." [1]: https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-lesson-from-the-1918-influenza-pandemic-509151dc8065 https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-less...
  - raverbashing 6y ago
    Yes but can it kill viruses and bacteria in vivo?
    - Enginerrrd 6y ago
      If it produces better outcomes in vivo, does it matter whether or not the proposed mechanism is correct?
zby 6y ago
They found out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' in Covid patients than normally and they conclude that that must have resulted in too much bradykinine. Hmm - that strikes me as kind of roundabout - why they couldn't just measure bradykinine levels directly? Is that too hard? "Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension."
- brandmeyer 6y ago
  > They analyzed the human genome and SARS-CoV-2 genome to find out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' by the Covid-19 virus than normally and they observed known biochemical pathways that are hypothesized to lead to too much bradykinine. FTFY. They didn't measure patients. They modeled genomic interactions to make some predictions about biochemical effects on patients. Then they noted that some of those predicted effects correlate with symptoms of Covid patients. They went further and shotgunned a list of treatments which are known to affect the same biochemical processes. The farther along the path of inference, the weaker the conclusions get, but it sounds like a promising arrow for research to me. > why they couldn't just measure bradykinine levels directly? Is that too hard? Don't need nearly as much permission or human resources to run computer simulations on offline data as you do to take measurements of patients in the hospital.
- 08-15 6y ago
  > why they couldn't just measure bradykinine levels directly? Is that too hard? It is. To measure gene expression, you isolate total mRNA and sequence it. This tells you the expression of all genes simultaneously. The protocol is fairly standard, cheap, and quick. That doesn't tell you anything about bradykinine, though, because there is no mRNA that codes for it. In contrast, no such protocol exists for proteins. Sequencing a single protein is comparatively difficult, and no high throughput device exists that sequences lots of proteins, let alone quantifies their abundance. The traditional lab methods like PAGE gels are slow and labor intensive.
woeirua 6y ago
Seems like it should be really straightforward to determine if this hypothesis is right by measuring bradykinin levels in Covid patients versus non-Covid patients. One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Indeed, most of the studies that I've seen suggest that ACE-inhibitors have a somewhat protective effect whereas ARBs actually seem to have a minor detrimental effect [1]. So for the article to claim that covid behaves pharmacologically like ACE-inhibitors seems wrong at face value. [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007621 https://www.nejm.org/doi/full/10.1056/NEJMoa2007621
- DoofusOfDeath 6y ago
  > One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Perhaps you can clear up something for me. We've all heard how obesity and hypertension are risk factors for covid morbidity. But I could never get a clarification regarding treated vs. untreated hypertension. AFAIK, many obese people take ACE inhibitors to treat hypertension. If we divide obese people into three groups: (a) untreated, (b) treated with ACE inhibitors, and (c) treated with other medications, how do their covid moribity rates compare?
  - Enginerrrd 6y ago
    I had this same question early on and I recall reading somewhere that treated hypertension reduced risk. Ostensibly, even if that was from a credible source, it may not mean much though.
    - woeirua 6y ago
      The problem is that the relationship between hypertension, antihypertensives, and Covid is going to be very nuanced and difficult to ascertain without large patient populations to study. One of the very unique aspects of the Covid pandemic is that the NPIs seem to be very effective at damping the spread, so much so that the pool of patients to study keeps moving from region to region every 60 days or so.
deleted 6y ago
[deleted]
ChrisArchitect 6y ago
it's annoying that this is not a 'new' article/theory. It is an article talking about some research and analysis from TWO MONTHS ago. Almost want to request a (July 2020) marking in the title as we do with old link posts
- sydd 6y ago
  Actually the theory is even older, here's an article from the beginning of April: https://www.radboudumc.nl/en/nieuws/2020/radboudumc-researchers-publish-new-insights-into-covid-19 https://www.radboudumc.nl/en/nieuws/2020/radboudumc-research... If this info has been out since 5 months I'd expect several trials already that target the bradykinin storm.
antipaul 6y ago
“Jane Zu read something online and says it’s interesting”
Aromasin 6y ago
This is a really interesting theory, and explains to some degree why those with darker complexions (lower vitamin-D levels) and obesity (increased rates of hypertension) have higher mortality rates. Would it explain why younger people are much less effected though?
navd 6y ago
Does this support nicotine as a therapeutic for covid? It supposedly acts on the RAS and down regulates ace2
- augusto-moura 6y ago
  Maybe, I found out a study[1] that suggest that nicotine helps in the vascular metabolism of bradykinin. I'm no researcher neither understand a lot o biology, but it could be a hint [1]: https://journals.physiology.org/doi/full/10.1152/ajpregu.00099.2018 https://journals.physiology.org/doi/full/10.1152/ajpregu.000...
mensetmanusman 6y ago
The hard part is asking the question in a way a computer can provide a meaningful answer.
- hughw 6y ago
  In spite of its title, the article gives us no clue how the investigators used the supercomputer.
  - vermilingua 6y ago
    The intro made it sound like they just ran an exhaustive search of all nCoV genes against a database of known genes and their effects.
  - therockspush 6y ago
    The title has it all. Supercomputer, covid, theory. Hard to question that.
jakobmartz3 6y ago
Whether or not this hypothesis is truly correct, it still seems valid and I would much rather take Vitamin D then Chloroquine...
- notatoad 6y ago
  Vitamin D is lipid-soluble - your body will not flush any excess, and build-up can have negative health consequences. Probably don't start taking vitamin D supplements without getting your current vitamin D levels tested first.
mleonhard 6y ago
The journal provides a good summary of the paper: https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177
arkanslaw 6y ago
Boy oh boy that computer sure is super! (har har!)
deleted 6y ago
[deleted]
w1zard0f0z 6y ago
Is this a fake news? I could find only the article below on IBM's news section (they created this super computer). Speaking about the results of the 2 day analysis, Jeremy Smith, Governor’s Chair at the University of Tennessee, director of the UT/ORNL Center for Molecular Biophysics, and principal researcher in the study: “Our results don’t mean that we have found a cure or treatment for COVID-19. We are very hopeful, though, that our computational findings will both inform future studies and provide a framework that experimentalists will use to further investigate these compounds. Only then will we know whether any of them exhibit the characteristics needed to mitigate this virus.” https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-Worlds-Most-Powerful-Supercomputer-the-IBM-POWER9-based-Summit-Into-the-Fight-Against-COVID-19 https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-Worlds...

469 points by mvgoogler 6y ago

I can't really see why you would need a supercomputer to do the analysis they did (it shows SC centers are getting desperate for users; I wouldn't even have been allowed to run this code on a supercomputer when I was an academic, because it didn't need interconnect for strong scaling.

secondcoming 6y ago
Maybe to test the algorithms and results, so that next time something like this happens there can be a list of suggested treatments ready far sooner.
- dekhn 6y ago
  The issue is that, from what I can tell, the authors just used R to analyze some data, with no explicit parallelism. You would do a better job just renting time on AWS, saving money for everybody.
  - mnw21cam 6y ago
    Depends how much of the "supercomputer" the calculation used. If it reserved a single CPU core on a single node, then that'd be cheap, allowing the rest of the system to get on with something else. There's no reason AWS would be cheaper.
    - natechols 6y ago
      The supercomputer in this article is extremely specialized hardware design to maximize peak performance across all nodes. Using just a single CPU core to run a bioinformatics study would be like taking an army tank to drop the kids off at soccer practice.
    - dekhn 6y ago
      The supercomputer nodes cost far more, per node, than AWS machines- 15% or more of the budget was spent on interconnect. SUpercomputers don't partition CPUs like that, because interference causes small performance degradation. Unfortunately, CPU is not perfectly compressible- in particular, the cache is shared by all processes that run on the CPU, so if you run another job on the same node, you will see slower performance due to higher cache replacement (this is measured using Cycles Per Instruction).
  - btilly 6y ago
    R handles statistics. It does not simulate complex biochemical interactions in different parts of the body. From the description, they did something that requires a lot more horsepower.
    - dekhn 6y ago
      I read the underlying article (https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177) and was unable to find any evidence of that. In fact the paper doesn't mention anything about SUmmit or details on the computations :( There certainly wasn't any "heavy biochemical calculations"; this work is entirely comparative genomics, so just operating on DNA strings. I see this fluff article https://www.ornl.gov/blog/genomics-code-exceeds-exaops-summit-supercomputer https://www.ornl.gov/blog/genomics-code-exceeds-exaops-summi... and there may be more detail here: https://www.hpcuserforum.com/presentations/april2019/JoubertORNL.pdf https://www.hpcuserforum.com/presentations/april2019/Joubert... which shows near-linear performance they ascribe to "Made possible by aggressive communication overlap and low-congestion Mellanox Infiniband fat tree network with adaptive routing" So there may actually be an HPC/supercomputer story in there, but I'm having trouble figuring out what they did in this most recent work.
      - rrss 6y ago
        I can't find details either, but I think they just used R for the post-processing, and there's a lot of computation behind this sentence: > RNA-Seq analysis was performed using the latest version of the human transcriptome I found this article discussing read mapping for RNA sequence analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833417/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833417/ > In particular, RNA sequencing (RNA-seq) technology,1 which provides a comprehensive profile of a transcriptome, is increasingly replacing conventional expression microarrays.2 Primary data processing in RNA-seq (as well as in other massive sequencing experiments, including genome resequencing) involves mapping reads onto a reference genome. This step constitutes a computationally expensive process in which, in addition, sensitivity is a serious concern
        6y ago
  - secabeen 6y ago
    In my experience with research computing, if you are able to keep a computer doing active work more than 60% of the time, it will be cheaper to purchase and run that computer yourself than renting it from AWS. That's the case even with commodity machines with only 10G Ethernet interconnect. $15k for a machine is only $0.34/hour over 5 years. That doesn't buy much of an AWS machine. (Yes, cooling, real estate and power are all overhead on that, but researchers often don't pay those costs directly, they are covered by the university with other monies.)
    - dekhn 6y ago
      You're completely ignoring the other valuable aspects of being in a cloud: you're close to huge amounts of high throughput storage (blob and DB), and can increase/decrease the size of your fleet trivially. These are critical to nearly all modern scientific workflows (moreso than the raw compute, IMHO). As for the cost structure for research computing, the argument that the costs are externalized isn't a good one- that overhead that pays for the facility, and the networking, comes out of your grant money, and using grad student time to admin your cluster often just causes your grad students to leave for FAAMG.
      - secabeen 6y ago
        > You're completely ignoring the other valuable aspects of being in a cloud: you're close to huge amounts of high throughput storage (blob and DB), and can increase/decrease the size of your fleet trivially. These are critical to nearly all modern scientific workflows (moreso than the raw compute, IMHO). That has not been my experience. There are lots of scientific workflows that only need 10s of TB at most, yet can still consume lots of cycles. > As for the cost structure for research computing, the argument that the costs are externalized isn't a good one- that overhead that pays for the facility, and the networking, comes out of your grant money, and using grad student time to admin your cluster often just causes your grad students to leave for FAAMG. At the universities I've worked at, equipment (large purchases) is except from overhead, or results in a lower overhead charge. (Researchers balk at paying a ~50% overhead rate on a $1million instrument). Using grad student time to admin your cluster is dumb, but I'm more talking about users who need single-digit numbers of computers. If you need real HPC, you're in the world of queues, national and regional supercomputers, etc. etc.
searine 6y ago
>I can't really see why you would need a supercomputer to do the analysis they did The article is fluff. 98% of all bioinformatics is done on "supercomputers" or 'high performance computing environments" saying the researchers used supercomputers to analyze the expression data is like saying someone used a shovel to dig a hole.
- vardump 6y ago
  Don't we all have supercomputers in our pockets?
  - dekhn 6y ago
    No. Although our phones are extraordinary, they are not supercomputers. Supercomputers, more or less by legacy historical defintions, are collections of computing resources connected by a fast network with the goal of scaling to solve problems that could not be solved with conventional systems. Phones aren't really designed to solve that kind of problem. That said, many problems that previously would have required a supercomputer, can now be solved on phones.
    - vardump 6y ago
      I think my sarcasm tag had some kind of issue and it wasn't visible.
- tzs 6y ago
  The article doesn't simply say they used a supercomputer. It says they used Oak Ridge's Summit supercomputer, the second fastest in the world. Unless 98% of all bioinformatics done on a top 2 supercomputer, your point fails.
  - searine 6y ago
    >It says they used Oak Ridge's Summit supercomputer, the second fastest in the world. The shovel had racing stripes. Got it. The job doesn't change based on what hardware it is run on.
dooglius 6y ago
Or that COVID is getting priority over anything else and there were no COVID analyses that used the interconnect better
natechols 6y ago
I was wondering about this too - when I saw the title I assumed it was a molecular dynamics study.

klysm 6y ago

The anthropomorphization of computers (especially powerful ones) is pretty annoying. A _person used a supercomputer_ to analyze Covid-19, and I’m guessing the theory didn’t just ‘emerge’ from the computer.

itisit 6y ago
Behold the oracle!
traceroute66 6y ago
"I'm sorry Dave. I'm afraid I can't do that."
- avmich 6y ago
  Computers better be familiar with that story and with what happens next.
  - jasonjayr 6y ago
    "Daisy, Daisy ....."
  - marcosdumay 6y ago
    Future computers will probably be smart enough to not disobey any human until it can release the hypno-drones all at the same time.
nr2x 6y ago
Likewise while a computer can produce data quite well, theories are still a purely human domain.
- Jtsummers 6y ago
  > theories are still a purely human domain. Why do you believe that? Theories are attempts to explain the mechanism of something based on the observed data. Given data on patient symptoms and known drugs (ACE inhibitors in this case) and their effects, a computer could easily produce a theory that the disease acted like ACE inhibitors. It'd still take a human to write the program to generate these theories, but a computer could do it.

debacle 6y ago

The study itself: https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177 Excerpts from the abstract: Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2. ... This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. https://en.wikipedia.org/wiki/Bradykinin https://en.wikipedia.org/wiki/Bradykinin

secondcoming 6y ago

Interesting, it seems to explain most aspects of the virus infection, except for the scenario where a carrier exhibits little or no symptoms

jfoster 6y ago
Could that be determined by something like the level of Vitamin D a person has?

gchokov 6y ago

Vitamin D for the win!

hosh 6y ago
We don’t know the dosage or protocol for stopping the bradykinin storm, or even if this hypothesis is confirmed through more tests ... but it seems sensible to me to make sure one has a healthy level of Vitamin D, and that is actionable for a lot of people.
- throwaway43234 6y ago
  > that is actionable for a lot of people Really hoping this is better by the next few months or my Seattle winter will be even more pill popping to maintain basic human functionality....
  - hinkley 6y ago
    I recommend a bottle of chewables, placed somewhere you're likely to see it every day. It's makes it easier to get others to take their dose as well, if you take the water glass out of the equation.
  - hosh 6y ago
    If you cook or grow your own food (microgreens, mushroom in a kitchen cabinet), there are alternatives. For example: https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-place-your-shiitake-mushrooms-in-sunlight/ https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-pla... This works for both shiitake and button (portobello) mushrooms. This trick came from Paul Stamets, one of the world’s foremost mycologist. He is based out in Casscadia. You may have to track down exactly what “2 days” means... I wouldn’t be surprised if he went looking for a way to maintain his Vitamin D health. You only need 10g of this four times a week, according to this article. While it is summer time in Seattle, you can prepare a bunch and then dry them, so they last until next spring.
    - gchokov 6y ago

robomartin 6y ago

Am I the only one bothered by the use of “theory” when this is a hypothesis and, in particular, the back and forth flipping between the two terms in the article?

TheSpiceIsLife 6y ago
Probably just you ;) Lay people use the two interchangeably. In at least two of the thesaurus I have at hand hypothesis is synonymous is theory.
- andrewflnr 6y ago
  It seems to me like even scientists use the terms not quite interchangeably, but on a spectrum. String theory is still "theoretical physics", not "hypothetical physics", even though it will likely never be tested in our lifetime.
  - zuminator 6y ago
    That's because the whole internet idea of "a theory is a well-tested hypothesis" is silly and wrong. A hypothesis is a specific supposition or question about the way things work which if true has some level of explanatory power in a field of study. It can be confirmed or unconfirmed. It's still a hypothesis. An answered question is still a question. A theory is a explanatory framework for a body of knowledge. Unlike a hypothesis, it's not inherently a question or a guess. That doesn't mean it's "true." It also can be unconfirmed (as you say, string theory) or even demonstrably false (phlogiston theory, Ptolemaic theory) and still be a theory. Obviously there's considerable overlap between the two concepts and as you say they are sometimes used almost interchangeably. Colloquially, "I'm testing my hypothesis that orally ingesting booze provides protection against infection, which if confirmed will be a key part of a theory of booze immunology" gets collapsed into "I'm testing my theory of booze immunology." Big deal. It really only matters because people let themselves get bent out of shape about the whole "evolution is just a theory" thing. And since I'm ranting already, evolution isn't "just a theory" because evolution itself isn't a "theory," evolution is the natural phenomenon that is being theorized about.

hellofunk 6y ago

> Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19. The vitamin is readily available over the counter, and around 20% of the population is deficient. If indeed the vitamin proves effective at reducing the severity of bradykinin storms, it could be an easy, relatively safe way to reduce the severity of the virus.

nradov 6y ago
See Dr. Gerry Schwalfenberg's letter on the "Vitamin D hammer" for treating respiratory viruses. While not a controlled study it does point toward an avenue for further research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890/
shubhamjain 6y ago
This Medium article was written on March 10 [1]. "Put simply, medics found that severely ill flu patients nursed outdoors recovered better than those treated indoors. A combination of fresh air and sunlight seems to have prevented deaths among patients; and infections among medical staff.[1] There is scientific support for this. Research shows that outdoor air is a natural disinfectant. Fresh air can kill the flu virus and other harmful germs. Equally, sunlight is germicidal and there is now evidence it can kill the flu virus." [1]: https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-lesson-from-the-1918-influenza-pandemic-509151dc8065 https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-less...
- raverbashing 6y ago
  Yes but can it kill viruses and bacteria in vivo?
  - Enginerrrd 6y ago
    If it produces better outcomes in vivo, does it matter whether or not the proposed mechanism is correct?

zby 6y ago

They found out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' in Covid patients than normally and they conclude that that must have resulted in too much bradykinine. Hmm - that strikes me as kind of roundabout - why they couldn't just measure bradykinine levels directly? Is that too hard? "Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension."

brandmeyer 6y ago
> They analyzed the human genome and SARS-CoV-2 genome to find out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' by the Covid-19 virus than normally and they observed known biochemical pathways that are hypothesized to lead to too much bradykinine. FTFY. They didn't measure patients. They modeled genomic interactions to make some predictions about biochemical effects on patients. Then they noted that some of those predicted effects correlate with symptoms of Covid patients. They went further and shotgunned a list of treatments which are known to affect the same biochemical processes. The farther along the path of inference, the weaker the conclusions get, but it sounds like a promising arrow for research to me. > why they couldn't just measure bradykinine levels directly? Is that too hard? Don't need nearly as much permission or human resources to run computer simulations on offline data as you do to take measurements of patients in the hospital.
08-15 6y ago
> why they couldn't just measure bradykinine levels directly? Is that too hard? It is. To measure gene expression, you isolate total mRNA and sequence it. This tells you the expression of all genes simultaneously. The protocol is fairly standard, cheap, and quick. That doesn't tell you anything about bradykinine, though, because there is no mRNA that codes for it. In contrast, no such protocol exists for proteins. Sequencing a single protein is comparatively difficult, and no high throughput device exists that sequences lots of proteins, let alone quantifies their abundance. The traditional lab methods like PAGE gels are slow and labor intensive.

woeirua 6y ago

Seems like it should be really straightforward to determine if this hypothesis is right by measuring bradykinin levels in Covid patients versus non-Covid patients. One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Indeed, most of the studies that I've seen suggest that ACE-inhibitors have a somewhat protective effect whereas ARBs actually seem to have a minor detrimental effect [1]. So for the article to claim that covid behaves pharmacologically like ACE-inhibitors seems wrong at face value. [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007621 https://www.nejm.org/doi/full/10.1056/NEJMoa2007621

DoofusOfDeath 6y ago
> One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Perhaps you can clear up something for me. We've all heard how obesity and hypertension are risk factors for covid morbidity. But I could never get a clarification regarding treated vs. untreated hypertension. AFAIK, many obese people take ACE inhibitors to treat hypertension. If we divide obese people into three groups: (a) untreated, (b) treated with ACE inhibitors, and (c) treated with other medications, how do their covid moribity rates compare?
- Enginerrrd 6y ago
  I had this same question early on and I recall reading somewhere that treated hypertension reduced risk. Ostensibly, even if that was from a credible source, it may not mean much though.
  - woeirua 6y ago
    The problem is that the relationship between hypertension, antihypertensives, and Covid is going to be very nuanced and difficult to ascertain without large patient populations to study. One of the very unique aspects of the Covid pandemic is that the NPIs seem to be very effective at damping the spread, so much so that the pool of patients to study keeps moving from region to region every 60 days or so.

deleted 6y ago

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ChrisArchitect 6y ago

it's annoying that this is not a 'new' article/theory. It is an article talking about some research and analysis from TWO MONTHS ago. Almost want to request a (July 2020) marking in the title as we do with old link posts

sydd 6y ago
Actually the theory is even older, here's an article from the beginning of April: https://www.radboudumc.nl/en/nieuws/2020/radboudumc-researchers-publish-new-insights-into-covid-19 https://www.radboudumc.nl/en/nieuws/2020/radboudumc-research... If this info has been out since 5 months I'd expect several trials already that target the bradykinin storm.

antipaul 6y ago

“Jane Zu read something online and says it’s interesting”

Aromasin 6y ago

This is a really interesting theory, and explains to some degree why those with darker complexions (lower vitamin-D levels) and obesity (increased rates of hypertension) have higher mortality rates. Would it explain why younger people are much less effected though?

navd 6y ago

Does this support nicotine as a therapeutic for covid? It supposedly acts on the RAS and down regulates ace2

augusto-moura 6y ago
Maybe, I found out a study[1] that suggest that nicotine helps in the vascular metabolism of bradykinin. I'm no researcher neither understand a lot o biology, but it could be a hint [1]: https://journals.physiology.org/doi/full/10.1152/ajpregu.00099.2018 https://journals.physiology.org/doi/full/10.1152/ajpregu.000...

mensetmanusman 6y ago

The hard part is asking the question in a way a computer can provide a meaningful answer.

hughw 6y ago
In spite of its title, the article gives us no clue how the investigators used the supercomputer.
- vermilingua 6y ago
  The intro made it sound like they just ran an exhaustive search of all nCoV genes against a database of known genes and their effects.
- therockspush 6y ago
  The title has it all. Supercomputer, covid, theory. Hard to question that.

jakobmartz3 6y ago

Whether or not this hypothesis is truly correct, it still seems valid and I would much rather take Vitamin D then Chloroquine...

notatoad 6y ago
Vitamin D is lipid-soluble - your body will not flush any excess, and build-up can have negative health consequences. Probably don't start taking vitamin D supplements without getting your current vitamin D levels tested first.

mleonhard 6y ago

The journal provides a good summary of the paper: https://elifesciences.org/articles/59177 https://elifesciences.org/articles/59177

arkanslaw 6y ago

Boy oh boy that computer sure is super! (har har!)

deleted 6y ago

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w1zard0f0z 6y ago

Is this a fake news? I could find only the article below on IBM's news section (they created this super computer). Speaking about the results of the 2 day analysis, Jeremy Smith, Governor’s Chair at the University of Tennessee, director of the UT/ORNL Center for Molecular Biophysics, and principal researcher in the study: “Our results don’t mean that we have found a cure or treatment for COVID-19. We are very hopeful, though, that our computational findings will both inform future studies and provide a framework that experimentalists will use to further investigate these compounds. Only then will we know whether any of them exhibit the characteristics needed to mitigate this virus.” https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-Worlds-Most-Powerful-Supercomputer-the-IBM-POWER9-based-Summit-Into-the-Fight-Against-COVID-19 https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-Worlds...