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This is basically chaos engineering applied the the genome It doesn't say "this gene has this outcome" so much as it says "this outcome fails when this byte of

This is basically chaos engineering applied the the genome It doesn't say "this gene has this outcome" so much as it says "this outcome fails when this byte of data is missing"

david_l_lin 4y ago
Not really? It says that some genes result in the same outcome when knocked out as other genes, and identifies novel genes that putatively participate in the same pathways as others. This helps get at the potential function of genes without known functions.
- dekhn 4y ago
  So, people do this a lot and frequently make mistakes. For example, when you knock out a gene, you also damage any overlapping genes (yes, genes can overlap). most studies don't pay attention to the damage they do to overlapping genes. The underlying physical model for how gene products interact to make phenotypes ends up being so hopelessly complex and latent that most conclusions in this area end up being "sufficient, but not necessary" instead of "necessary, but not sufficient"
- jazzyjackson 4y ago
  > It says that some genes result in the same outcome when knocked out as other genes a very useful map to make, but I don't see that this contradicts my comment - both genes in this case are dependencies to the outcome, without either of them, the outcome fails this does not sound to me like we know the "function" of these genes, only that they're nessary for each phenotype not to knock the research, just trying to make sense of what they're really mapping, in my own language of computer code (i suppose "function" has a different connotation in genetics)
  - timy2shoes 4y ago
    > this does not sound to me like we know the "function" of these genes, only that they're nessary for each phenotype But they're not even measuring the phenotype. They're using the transciptional signature as a substitute for phenotype/cell function (i.e. the bag of RNA model). This is a poor substitute if you try to apply this to practical applications such as cell engineering. Let's say I perturb a cell to match it's transcriptional signature to that of a neuron. Does that make it a neuron? Not if it doesn't function like a neuron.
    - twic 4y ago
      I think this is a really important point. With a few exceptions (like the neat implied aneuploidy assay), they haven't measured an outcome or phenotype for the genes. They have measured the impact on transcription (well, mRNA levels, via transcription or some other effect). That is an extremely useful dataset, but it's not enough to say what the phenotypic effect of knocking out any given gene is, much less what the actual mechanistic function of the gene product is. It's also important to note that there are loads of genes whose effects are not mediated by changes in mRNA levels. If you knock out Arp2, a cell can't move properly, because Arp2 is involved in assembling cytoskeletal structures needed to do that, but you probably won't be able to tell that by looking at the cell's mRNA.
  - david_l_lin 4y ago
    > "this outcome fails when this byte of data is missing" The outcomes here are not failures, they are measurable phenotypic differences, which they use to group genes into phenotypic outcomes. The typical "knockout -> failure to perform a function" is not what's being measured here.
throwawaycities 4y ago
About 18-24months ago I went through a phase of listening to geneticists talks/conferences/podcasts for an hour or two a day during long runs, it’s so far outside my wheelhouse I’m probably mixing things up, but I thought I recalled cutting edge experiments using synthetic cells to create artificial life (a worm perhaps with a relatively simple DNA, maybe even a modified DNA further simplifying the genome to the furthest extent possible still resulting in life) with one of the goals of understanding the exact functions of all the genes in this “simple” DNA. Again I’m probably mixing up multiple discussions and studies into one, but I would have been very surprised if the function of every single gene in the human genome was known and understood, as suggested by the title.
- dekhn 4y ago
  I worked with mycoplasma genitalium which is a "minimal" organism- an extremely small number of genes, nearly all of which appear to be absolutely required for viability. It's sort of a unit test for model biology, except it grows so slowly it's more like an integration test in terms of performance. You are probably referring to Mycoplasma genitalium JCVI-1.0 ( (see https://en.wikipedia.org/wiki/Mycoplasma_genitalium https://en.wikipedia.org/wiki/Mycoplasma_genitalium) as worms are too complex to be minimialized See also https://en.wikipedia.org/wiki/Mycoplasma_laboratorium https://en.wikipedia.org/wiki/Mycoplasma_laboratorium The work in this area is quite extraordinary, but typically gets much less attention than anything that works with human genomes.
  - gilleain 4y ago
    Hmm wonder how Craig Venter is getting along with his project. He was making a lot of noise about it a few years ago. Seems like he sold a company in April of this year to the University of California.
  - lgas 4y ago
    Maybe https://en.wikipedia.org/wiki/Caenorhabditis_elegans#Use_as_a_model_organism https://en.wikipedia.org/wiki/Caenorhabditis_elegans#Use_as_... ?
Victerius 4y ago
Designer babies incoming. Turn off the genes that would make my child below 6'5 in adulthood, turn off the genes that wouldn't make him naturally muscular, turn off the genes that would give him an average intelligence, etc. $10M + options. Payable in monthly installments.
- zen_1 4y ago
  Turn on the Myostatin inhibitors!
- WitCanStain 4y ago
  A new genetic aristocracy. Great.
  - elif 4y ago
    Yea human culture will find a new level of 'basic' combined with an inferred and understood if not blatantly codified position of social superiority... Sounds more like twilight zone than social progress to me.
- fgkramer 4y ago
  We just need to see Gattaca to be horrified at the results of such experiment.
  - sneak 4y ago
    I have seen Gattaca and don't find human genetic engineering to be horrific. It's cool and exciting that people will be able to have better children than they would have otherwise.
    - nescioquid 4y ago
      > It's cool and exciting that people will be able to have better children than they would have otherwise. You know, I used to be wary of eugenics, but when you put in that light, yeah, I'm kinda tired of putting up with everyone's crap kids. If you could make them be quiet, sit still, and do as told, that would be a fantastic achievement! Oh, and maybe make them smarter, too. Ever try to actually talk to one (the newer ones are really pretty stupid)?
ramraj07 4y ago
Not sure if you’re doing it a service or disservice calling it chaos engineering: at best it’s related. If you want to figure out what a complex system does where you have no ability to “see”, the only tool you have most of the time is to knock out individual components and see what happens. As you might guess this is generally a blunt tool which can help you get to the first 30% of the understanding of the system but minimal extra data after that. The majority of genes discovered in this study would either be already known players in those pathways or unknown genes that would already have been guessed to play a role. Until one of these massive screens tells us what the major vault protein complex does they should all be honest about what they are which Imo is just a minor addition.
pishpash 4y ago
It's kind of a dead end I feel. It can turn out that everything is used for everything. It's not designed so there is probably no clean decomposition nor is it necessary.
deleted 4y ago
[deleted]

This is basically chaos engineering applied the the genome It doesn't say "this gene has this outcome" so much as it says "this outcome fails when this byte of data is missing"

david_l_lin 4y ago

Not really? It says that some genes result in the same outcome when knocked out as other genes, and identifies novel genes that putatively participate in the same pathways as others. This helps get at the potential function of genes without known functions.

dekhn 4y ago
So, people do this a lot and frequently make mistakes. For example, when you knock out a gene, you also damage any overlapping genes (yes, genes can overlap). most studies don't pay attention to the damage they do to overlapping genes. The underlying physical model for how gene products interact to make phenotypes ends up being so hopelessly complex and latent that most conclusions in this area end up being "sufficient, but not necessary" instead of "necessary, but not sufficient"
jazzyjackson 4y ago
> It says that some genes result in the same outcome when knocked out as other genes a very useful map to make, but I don't see that this contradicts my comment - both genes in this case are dependencies to the outcome, without either of them, the outcome fails this does not sound to me like we know the "function" of these genes, only that they're nessary for each phenotype not to knock the research, just trying to make sense of what they're really mapping, in my own language of computer code (i suppose "function" has a different connotation in genetics)
- timy2shoes 4y ago
  > this does not sound to me like we know the "function" of these genes, only that they're nessary for each phenotype But they're not even measuring the phenotype. They're using the transciptional signature as a substitute for phenotype/cell function (i.e. the bag of RNA model). This is a poor substitute if you try to apply this to practical applications such as cell engineering. Let's say I perturb a cell to match it's transcriptional signature to that of a neuron. Does that make it a neuron? Not if it doesn't function like a neuron.
  - twic 4y ago
    I think this is a really important point. With a few exceptions (like the neat implied aneuploidy assay), they haven't measured an outcome or phenotype for the genes. They have measured the impact on transcription (well, mRNA levels, via transcription or some other effect). That is an extremely useful dataset, but it's not enough to say what the phenotypic effect of knocking out any given gene is, much less what the actual mechanistic function of the gene product is. It's also important to note that there are loads of genes whose effects are not mediated by changes in mRNA levels. If you knock out Arp2, a cell can't move properly, because Arp2 is involved in assembling cytoskeletal structures needed to do that, but you probably won't be able to tell that by looking at the cell's mRNA.
- david_l_lin 4y ago
  > "this outcome fails when this byte of data is missing" The outcomes here are not failures, they are measurable phenotypic differences, which they use to group genes into phenotypic outcomes. The typical "knockout -> failure to perform a function" is not what's being measured here.

throwawaycities 4y ago

About 18-24months ago I went through a phase of listening to geneticists talks/conferences/podcasts for an hour or two a day during long runs, it’s so far outside my wheelhouse I’m probably mixing things up, but I thought I recalled cutting edge experiments using synthetic cells to create artificial life (a worm perhaps with a relatively simple DNA, maybe even a modified DNA further simplifying the genome to the furthest extent possible still resulting in life) with one of the goals of understanding the exact functions of all the genes in this “simple” DNA. Again I’m probably mixing up multiple discussions and studies into one, but I would have been very surprised if the function of every single gene in the human genome was known and understood, as suggested by the title.

dekhn 4y ago
I worked with mycoplasma genitalium which is a "minimal" organism- an extremely small number of genes, nearly all of which appear to be absolutely required for viability. It's sort of a unit test for model biology, except it grows so slowly it's more like an integration test in terms of performance. You are probably referring to Mycoplasma genitalium JCVI-1.0 ( (see https://en.wikipedia.org/wiki/Mycoplasma_genitalium https://en.wikipedia.org/wiki/Mycoplasma_genitalium) as worms are too complex to be minimialized See also https://en.wikipedia.org/wiki/Mycoplasma_laboratorium https://en.wikipedia.org/wiki/Mycoplasma_laboratorium The work in this area is quite extraordinary, but typically gets much less attention than anything that works with human genomes.
- gilleain 4y ago
  Hmm wonder how Craig Venter is getting along with his project. He was making a lot of noise about it a few years ago. Seems like he sold a company in April of this year to the University of California.
- lgas 4y ago
  Maybe https://en.wikipedia.org/wiki/Caenorhabditis_elegans#Use_as_a_model_organism https://en.wikipedia.org/wiki/Caenorhabditis_elegans#Use_as_... ?

Victerius 4y ago

Designer babies incoming. Turn off the genes that would make my child below 6'5 in adulthood, turn off the genes that wouldn't make him naturally muscular, turn off the genes that would give him an average intelligence, etc. $10M + options. Payable in monthly installments.

zen_1 4y ago
Turn on the Myostatin inhibitors!
WitCanStain 4y ago
A new genetic aristocracy. Great.
- elif 4y ago
  Yea human culture will find a new level of 'basic' combined with an inferred and understood if not blatantly codified position of social superiority... Sounds more like twilight zone than social progress to me.
fgkramer 4y ago
We just need to see Gattaca to be horrified at the results of such experiment.
- sneak 4y ago
  I have seen Gattaca and don't find human genetic engineering to be horrific. It's cool and exciting that people will be able to have better children than they would have otherwise.
  - nescioquid 4y ago
    > It's cool and exciting that people will be able to have better children than they would have otherwise. You know, I used to be wary of eugenics, but when you put in that light, yeah, I'm kinda tired of putting up with everyone's crap kids. If you could make them be quiet, sit still, and do as told, that would be a fantastic achievement! Oh, and maybe make them smarter, too. Ever try to actually talk to one (the newer ones are really pretty stupid)?

ramraj07 4y ago

Not sure if you’re doing it a service or disservice calling it chaos engineering: at best it’s related. If you want to figure out what a complex system does where you have no ability to “see”, the only tool you have most of the time is to knock out individual components and see what happens. As you might guess this is generally a blunt tool which can help you get to the first 30% of the understanding of the system but minimal extra data after that. The majority of genes discovered in this study would either be already known players in those pathways or unknown genes that would already have been guessed to play a role. Until one of these massive screens tells us what the major vault protein complex does they should all be honest about what they are which Imo is just a minor addition.

pishpash 4y ago

It's kind of a dead end I feel. It can turn out that everything is used for everything. It's not designed so there is probably no clean decomposition nor is it necessary.

deleted 4y ago

[deleted]