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I have given a few genetics talks this past year to technical groups and I start the talk by saying "This is no more difficult to understand than any event bas

I have given a few genetics talks this past year to technical groups and I start the talk by saying "This is no more difficult to understand than any event based system" [insert image of the Netflix micro services architecture] This gets a laugh. DNA is like an executable file written in assembly. Most of the time it makes a bunch of pure functions (but not always) and it is self modifying, lol. For most of the work I do I can presume that gene X produces a "pure function" At the next level up you have a bunch of functions that can take some arguments and spits out some stuff. The question is does that function work etc? At the next level up you have systems thinking. If I have 100 lambda servers that are all executing from a queue and then I have 20 lambda servers that are all reading from those 100 you can guess where the data is going to pile up. I am radically over simplifying, but hopefully you see the parallels to binary, code, application logic In our "designed" software you can almost never go and change one line to modify the behavior of a program. Instead you have dozens if not millions of functions that all interact depending on the lens by which you want to look. Usually it is contained in on "area" with code that matters the most, but that isn't always the case. Is it any surprise that biology is even messier? The article mentions the 300 genes related to schizophrenia. This is like me mentioning that my random Go service also uses a bunch of Go standard library code when it is executing. Debugging stuff like this is what our careers are made of. For a long time scientist were looking for a single gay gene. Poking around once I knew what to look for it only took around 6 months to figure out the whole LGBT, but in nearly all cases it involves more than just one gene. You simply have to apply debugging logic at each layer to figure it out. It is handy to understand all the layers, but depending on the problem not always required.

picometer 3y ago
Wow - can you elaborate on your process to “debug” these different layers? What comprises your personal or team’s feedback loop, given that 6 months is short? (I suspect it’s a lot of sequencing?) Are there good comparisons to be made with getting acquainted with a new codebase/technical system? Are there any particular computational tools involved? Pardon all the questions, this stuff is fascinating!
- r0ze-at-hn 3y ago
  To be clear this is/was a hobby project. Getting access to DNA files is required yes, but sequencing wasn't really the limiting factor. It started with simply poking around my DNA file and then some friends many of which were only done on 23andme. Most of the time was spent reading countless papers and making hypothesis, trying to invalidate them and iterating. Constantly seeking out new ways to look at the problem and going from there. Every time I got a new DNA file from someone I could see how their dna fit into the current hypothesis. Because every DNA was different it was a great way to test them. It anything it made my job easier. I wasn't looking for a single snp, but common patterns. Sometimes this has involved using nebula and their whole genome sequencing dna test to get much more accurate data, but more often than not the cheap dna tests most people do were good enough. As for actual programs, I did write some quick and dirty scripts to scan dna files for specific snps, but mostly I would just read them as the parts I needed were not that long. There is a fair amount of phenotype data to start with. What ultimately started this was knowing 1) that there was a number of conditions that are seen in statistically weird numbers in the LGBT and 2) sex hormone levels in the LGBT are not exactly what you would expect. My goto fun question when talking with someone in the LGBT is if they have hypermobility. A good percentage do. In one specific example those with classical like EDS will have 21-OHD and thus POTS and elevated 17-OHP, backdoor DHT production (aka PCOS for women) etc. The real question I have been pondering is what exactly do I do with this as this is just a fun puzzle, not my job, I don't work for any school etc.
  - satokema 3y ago
    if nothing else post about it. everyone loves a good story.
  - justinclift 3y ago
    > what exactly do I do with this Whatever you do, maybe do it anonymously? It really sounds like it could badly trigger many people who will viciously attack others, actively attempt to destroy their lives, etc. Be careful? :)
  - calf 3y ago
    I don't get it. If you can solve for LGBT genes that easily, then why isn't this in the news? Surely academic scientists would have tried this if all you needed was some scripting to find patterns?
0134340 3y ago
If we're allowed to use computing analogies here, would it be fair to say the old model is more like how we view a standard CPU and the new model is more like a FPGA? Where the old model viewed genes in a more classic reductionist approach as CPUs, arranged and static logic waiting for input from the environment and impressing on the environment in such a deterministic way. While the newer model analogy, genes act as an FPGA, an array of gates with potential to adapt to input imposed upon them with this bi-directional synchronicity of environment impressing on genes and genes therefore impressing on environment? It seems as fields mature we move further away from classic reductionism and encompass more a holistic approach, a path gravitating towards objectivity which I find interesting from a philosophical perspective.
- r0ze-at-hn 3y ago
  For those old enough to program on punch cards you could say that is closer. We load the program into ram and then the env can and often does modify the program on the fly and we do dumb thing like use the current line number to save a byte because dividing by 17 is “good enough”. Most cards are functional and many cards do double or triple duty to save space. So a bug in one card can subtly break three wildly different spots. Analogies break down of course as in biology it all executes at the same time which is why the micro services or lamdas that can be scaled up or down have been my go to. And you can even inject external events into your lambda systems. And for anyone familiar with lisp, code is data, data is code. For modern coders you can think that it has a billion feature flags you can also flip on and off rather than rewriting the code on the fly
carlsborg 3y ago
Amazing perspective. Are any of the talks online?
bowsamic 3y ago
Sorry but this reads like complete gibberish to me. Could you write this again with less paragraph breaks?
FrustratedMonky 3y ago
Exactly this. Everyone arguing DNA isn't code, its just a reductive metaphor, and that the computer analogy is wrong, don't understand computers/code, or DNA. There is such a 1-1 correspondence, that the 'metaphor' begins to look more 'real'.

picometer 3y ago

Wow - can you elaborate on your process to “debug” these different layers? What comprises your personal or team’s feedback loop, given that 6 months is short? (I suspect it’s a lot of sequencing?) Are there good comparisons to be made with getting acquainted with a new codebase/technical system? Are there any particular computational tools involved? Pardon all the questions, this stuff is fascinating!

r0ze-at-hn 3y ago
To be clear this is/was a hobby project. Getting access to DNA files is required yes, but sequencing wasn't really the limiting factor. It started with simply poking around my DNA file and then some friends many of which were only done on 23andme. Most of the time was spent reading countless papers and making hypothesis, trying to invalidate them and iterating. Constantly seeking out new ways to look at the problem and going from there. Every time I got a new DNA file from someone I could see how their dna fit into the current hypothesis. Because every DNA was different it was a great way to test them. It anything it made my job easier. I wasn't looking for a single snp, but common patterns. Sometimes this has involved using nebula and their whole genome sequencing dna test to get much more accurate data, but more often than not the cheap dna tests most people do were good enough. As for actual programs, I did write some quick and dirty scripts to scan dna files for specific snps, but mostly I would just read them as the parts I needed were not that long. There is a fair amount of phenotype data to start with. What ultimately started this was knowing 1) that there was a number of conditions that are seen in statistically weird numbers in the LGBT and 2) sex hormone levels in the LGBT are not exactly what you would expect. My goto fun question when talking with someone in the LGBT is if they have hypermobility. A good percentage do. In one specific example those with classical like EDS will have 21-OHD and thus POTS and elevated 17-OHP, backdoor DHT production (aka PCOS for women) etc. The real question I have been pondering is what exactly do I do with this as this is just a fun puzzle, not my job, I don't work for any school etc.
- satokema 3y ago
  if nothing else post about it. everyone loves a good story.
- justinclift 3y ago
  > what exactly do I do with this Whatever you do, maybe do it anonymously? It really sounds like it could badly trigger many people who will viciously attack others, actively attempt to destroy their lives, etc. Be careful? :)
- calf 3y ago
  I don't get it. If you can solve for LGBT genes that easily, then why isn't this in the news? Surely academic scientists would have tried this if all you needed was some scripting to find patterns?

0134340 3y ago

If we're allowed to use computing analogies here, would it be fair to say the old model is more like how we view a standard CPU and the new model is more like a FPGA? Where the old model viewed genes in a more classic reductionist approach as CPUs, arranged and static logic waiting for input from the environment and impressing on the environment in such a deterministic way. While the newer model analogy, genes act as an FPGA, an array of gates with potential to adapt to input imposed upon them with this bi-directional synchronicity of environment impressing on genes and genes therefore impressing on environment? It seems as fields mature we move further away from classic reductionism and encompass more a holistic approach, a path gravitating towards objectivity which I find interesting from a philosophical perspective.

r0ze-at-hn 3y ago
For those old enough to program on punch cards you could say that is closer. We load the program into ram and then the env can and often does modify the program on the fly and we do dumb thing like use the current line number to save a byte because dividing by 17 is “good enough”. Most cards are functional and many cards do double or triple duty to save space. So a bug in one card can subtly break three wildly different spots. Analogies break down of course as in biology it all executes at the same time which is why the micro services or lamdas that can be scaled up or down have been my go to. And you can even inject external events into your lambda systems. And for anyone familiar with lisp, code is data, data is code. For modern coders you can think that it has a billion feature flags you can also flip on and off rather than rewriting the code on the fly

carlsborg 3y ago

Amazing perspective. Are any of the talks online?

bowsamic 3y ago

Sorry but this reads like complete gibberish to me. Could you write this again with less paragraph breaks?

FrustratedMonky 3y ago

Exactly this. Everyone arguing DNA isn't code, its just a reductive metaphor, and that the computer analogy is wrong, don't understand computers/code, or DNA. There is such a 1-1 correspondence, that the 'metaphor' begins to look more 'real'.