7 ms·

CS 522: Machine Learning Approaches to Decode the Human Genome

171 points by casawa 9y ago

casawa 9y ago
If of interest, other notes are available at cs522.stanford.edu and more will be available shortly!
- mchowdhury 9y ago
  +1
- visopsys 9y ago
  +1
- vrm 9y ago
  dude nice job getting exposure with this!
- indescions_2018 9y ago
  Yeah, definitely interested ;) Any chance the course has room for the other side of the coin? Namely, how neuroevolution and genetic strategies inform deep reinforcement learning? Am also interested in learning about the state-of-the-art in cloud based packages. I noticed recently Google released a tool called DeepVariant for use on their genomics platform. https://github.com/google/deepvariant https://github.com/google/deepvariant Creating a universal SNP and small indel variant caller with deep neural networks https://www.biorxiv.org/content/early/2018/01/09/092890 https://www.biorxiv.org/content/early/2018/01/09/092890
  - chillee 9y ago
    Answer: it doesn't. Genetic algorithms and the like are pretty much all terrible. They're ways of approximating your gradient, and fall to the curse of dimensionality. The only reason Uber and open.ai published their papers on evolutionary strategies (something pretty different from what people think of as genetic algorithms) is that current policy gradient methods are really bad as well, allowing what is effectively random search to do well. It's kinda like how Bayesian hyperparameter optimization is pretty terrible and 2x random search almost always beats it easily.
hateful 9y ago
Direct link to video (via link on top of site): https://www.youtube.com/watch?list=PLeEhPBsiwmeQPNgi1iHb4Bi4WO3NuYnX9&time_continue=3&v=lX76DzZdjvQ https://www.youtube.com/watch?list=PLeEhPBsiwmeQPNgi1iHb4Bi4...
zitterbewegung 9y ago
Can I give you my genome? Or will I be able to reproduce your methods from this site?
- maxander 9y ago
  This is a course on a fairly novel field of research, not a method to do anything remotely consumer-facing.
  - nextos 9y ago
    I disagree! It's a fantastic domain for startups! Nanopore is readily available. I have sequenced stuff in my kitchen, and I'm a computer scientist.
    - alsocasey 9y ago
      I haven't looked into their new minion much yet, but how cheap are really talking about?
    - maxander 9y ago
      DNA sequencing is mature and, if anything, almost getting to be late in the game for new startup entries. Determining gene function through ML methods is a whole different thing, and that's what I, and the OP, was talking about. Are we all responding to the same article here?
- sinab 9y ago
  I think there is an important distinction between sequencing a genome and then using ML methods to extract meaning from it. Sequencing (has traditionally) been hard but is now more of a tractable problem [1, 2]. To answer your question, if you have your genome and a dataset of known genomes marked with functions according to regions, then you could probably perform an interesting analysis.. [1] https://nanoporetech.com/ https://nanoporetech.com/ [2] https://www.illumina.com/ https://www.illumina.com/
proc0 9y ago
> Learning the DNA regulatory code of the genome This is so interesting. I cannot imagine what kind of language evolution chose to build on top of DNA. There must be some paradigm it maps to, and it's going to be incredibly interesting to see if a compiler/interpreter can be made for DNA, along with higher level languages that compile down to it.
- shaki-dora 9y ago
  If you’re interested, much of what you’re asking about is actually known: (some) DNA sequences map directly to protein sequences. Because DNA has a 4 letter alphabet (G, C, T, A), it takes three to map to one of the 2x different amino acids that make up proteins. Proteins, in turn, are the “machines” that work in cells. DNA also contains regulatory segments, errors, “dead” code left over (and carried through generations) long after it stopped being transcribed, DNA once inserted by viruses (both active and inactive) etc etc... If you want an analogy with computer code: it’s most like a spaghetti-code hair ball of assembly coding it’s own compiler, IDE, vim, a few games, and a neural network ten magnitudes the size of anything tensorflow can do. It does it all on hardware that works only probabilistically. And it is constantly starved for resources, leading to hacks such as DNA sequences that code for two completely different functioning proteins depending on reading it either forward or backward, or starting to read at an offset (what’s called a “reading frame”). There’s a thick book on molecular biology by Alberts et al. It’s the most phantastic deep dive into this, any many other, insanities. I believe Larry Page used to recommend it to all new googlers.
  - entee 9y ago
    MBOC is the book you're looking for by Alberts: https://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/dp/0815344325/ref=sr_1_2?ie=UTF8&qid=1519168605&sr=8-2&keywords=molecular+biology+of+the+cell https://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/... It's standard reading at the very least as intro grad/senior undergrad student in the biosciences. Great book, well written, well curated. Parent commenter is correct, DNA->function is massively complicated. The main wiki article to start with is: https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology https://en.wikipedia.org/wiki/Central_dogma_of_molecular_bio... As the article notes, there are endless exceptions and edge cases. It links to various examples of those.
JepZ 9y ago
Anybody knows why we cant just write a cell simulator and start experimenting that way with DNA manipulation? I mean I have no idea what the first nucleotides are for, but when I have a simulator I can try changing them and see what happens? This may sound like a naive approach, but is there anything special hindering us from building such a simulator or is it just that scientists will not find it useful as it will take too long before we know which nucleotides are important for our goals?
- landryraccoon 9y ago
  > Anybody knows why we cant just write a cell simulator This is hard. To my knowledge we can't even write most basic components of a cell simulator yet. One of the obvious requirements would be a protein folding simulator. Nobody has been able to come up with a working one of those yet. > when I have a simulator I can try changing them and see what happens? If you write a simulator that does this you will be a billionaire and probably win a Nobel prize in medicine while you're at it.
  - hoelle 9y ago
    Yep. I recently met a team working on this stuff at the Allen Institute for Cell Science. The problem space is huge and the field is totally in its infancy. If anyone is interested in this work, check their job site. Last I heard they were looking to hire a programmer to help write the sim. Cool team + science.
    - jjjensen90 9y ago
      Out of curiosity I checked their jobs site. What a cool opportunity, working in a nascent field of science at a prestigious institution. It was funny to notice that they seem to value a Bachelor's degree at a rate of higher than 1:1 with career experience: > 4-5 years of experience in a software development team AND a bachelor’s degree in computer science or a related field | OR 15+ years of relevant working experience... > 6-9 years of experience in a software development team AND a bachelor’s degree in computer science or a related field | OR 20+ years of relevant working experience That is a pretty heavy premium to put on those years during undergrad. I certainly wasn't as good by undergrad + 5 years as at 15+ years in the field, but maybe they know better than me.
davidgl 9y ago
For anyone would missed it, also see this great link on HN recently: https://news.ycombinator.com/item?id=16233644 https://news.ycombinator.com/item?id=16233644 - DNA seen through the eyes of a coder (2017)

171 points by casawa 9y ago

casawa 9y ago

If of interest, other notes are available at cs522.stanford.edu and more will be available shortly!

mchowdhury 9y ago
+1
visopsys 9y ago
+1
vrm 9y ago
dude nice job getting exposure with this!
indescions_2018 9y ago
Yeah, definitely interested ;) Any chance the course has room for the other side of the coin? Namely, how neuroevolution and genetic strategies inform deep reinforcement learning? Am also interested in learning about the state-of-the-art in cloud based packages. I noticed recently Google released a tool called DeepVariant for use on their genomics platform. https://github.com/google/deepvariant https://github.com/google/deepvariant Creating a universal SNP and small indel variant caller with deep neural networks https://www.biorxiv.org/content/early/2018/01/09/092890 https://www.biorxiv.org/content/early/2018/01/09/092890
- chillee 9y ago
  Answer: it doesn't. Genetic algorithms and the like are pretty much all terrible. They're ways of approximating your gradient, and fall to the curse of dimensionality. The only reason Uber and open.ai published their papers on evolutionary strategies (something pretty different from what people think of as genetic algorithms) is that current policy gradient methods are really bad as well, allowing what is effectively random search to do well. It's kinda like how Bayesian hyperparameter optimization is pretty terrible and 2x random search almost always beats it easily.

hateful 9y ago

Direct link to video (via link on top of site): https://www.youtube.com/watch?list=PLeEhPBsiwmeQPNgi1iHb4Bi4WO3NuYnX9&time_continue=3&v=lX76DzZdjvQ https://www.youtube.com/watch?list=PLeEhPBsiwmeQPNgi1iHb4Bi4...

zitterbewegung 9y ago

Can I give you my genome? Or will I be able to reproduce your methods from this site?

maxander 9y ago
This is a course on a fairly novel field of research, not a method to do anything remotely consumer-facing.
- nextos 9y ago
  I disagree! It's a fantastic domain for startups! Nanopore is readily available. I have sequenced stuff in my kitchen, and I'm a computer scientist.
  - alsocasey 9y ago
    I haven't looked into their new minion much yet, but how cheap are really talking about?
  - maxander 9y ago
    DNA sequencing is mature and, if anything, almost getting to be late in the game for new startup entries. Determining gene function through ML methods is a whole different thing, and that's what I, and the OP, was talking about. Are we all responding to the same article here?
sinab 9y ago
I think there is an important distinction between sequencing a genome and then using ML methods to extract meaning from it. Sequencing (has traditionally) been hard but is now more of a tractable problem [1, 2]. To answer your question, if you have your genome and a dataset of known genomes marked with functions according to regions, then you could probably perform an interesting analysis.. [1] https://nanoporetech.com/ https://nanoporetech.com/ [2] https://www.illumina.com/ https://www.illumina.com/

proc0 9y ago

> Learning the DNA regulatory code of the genome This is so interesting. I cannot imagine what kind of language evolution chose to build on top of DNA. There must be some paradigm it maps to, and it's going to be incredibly interesting to see if a compiler/interpreter can be made for DNA, along with higher level languages that compile down to it.

shaki-dora 9y ago
If you’re interested, much of what you’re asking about is actually known: (some) DNA sequences map directly to protein sequences. Because DNA has a 4 letter alphabet (G, C, T, A), it takes three to map to one of the 2x different amino acids that make up proteins. Proteins, in turn, are the “machines” that work in cells. DNA also contains regulatory segments, errors, “dead” code left over (and carried through generations) long after it stopped being transcribed, DNA once inserted by viruses (both active and inactive) etc etc... If you want an analogy with computer code: it’s most like a spaghetti-code hair ball of assembly coding it’s own compiler, IDE, vim, a few games, and a neural network ten magnitudes the size of anything tensorflow can do. It does it all on hardware that works only probabilistically. And it is constantly starved for resources, leading to hacks such as DNA sequences that code for two completely different functioning proteins depending on reading it either forward or backward, or starting to read at an offset (what’s called a “reading frame”). There’s a thick book on molecular biology by Alberts et al. It’s the most phantastic deep dive into this, any many other, insanities. I believe Larry Page used to recommend it to all new googlers.
- entee 9y ago
  MBOC is the book you're looking for by Alberts: https://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/dp/0815344325/ref=sr_1_2?ie=UTF8&qid=1519168605&sr=8-2&keywords=molecular+biology+of+the+cell https://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/... It's standard reading at the very least as intro grad/senior undergrad student in the biosciences. Great book, well written, well curated. Parent commenter is correct, DNA->function is massively complicated. The main wiki article to start with is: https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology https://en.wikipedia.org/wiki/Central_dogma_of_molecular_bio... As the article notes, there are endless exceptions and edge cases. It links to various examples of those.

JepZ 9y ago

Anybody knows why we cant just write a cell simulator and start experimenting that way with DNA manipulation? I mean I have no idea what the first nucleotides are for, but when I have a simulator I can try changing them and see what happens? This may sound like a naive approach, but is there anything special hindering us from building such a simulator or is it just that scientists will not find it useful as it will take too long before we know which nucleotides are important for our goals?

landryraccoon 9y ago
> Anybody knows why we cant just write a cell simulator This is hard. To my knowledge we can't even write most basic components of a cell simulator yet. One of the obvious requirements would be a protein folding simulator. Nobody has been able to come up with a working one of those yet. > when I have a simulator I can try changing them and see what happens? If you write a simulator that does this you will be a billionaire and probably win a Nobel prize in medicine while you're at it.
- hoelle 9y ago
  Yep. I recently met a team working on this stuff at the Allen Institute for Cell Science. The problem space is huge and the field is totally in its infancy. If anyone is interested in this work, check their job site. Last I heard they were looking to hire a programmer to help write the sim. Cool team + science.
  - jjjensen90 9y ago
    Out of curiosity I checked their jobs site. What a cool opportunity, working in a nascent field of science at a prestigious institution. It was funny to notice that they seem to value a Bachelor's degree at a rate of higher than 1:1 with career experience: > 4-5 years of experience in a software development team AND a bachelor’s degree in computer science or a related field | OR 15+ years of relevant working experience... > 6-9 years of experience in a software development team AND a bachelor’s degree in computer science or a related field | OR 20+ years of relevant working experience That is a pretty heavy premium to put on those years during undergrad. I certainly wasn't as good by undergrad + 5 years as at 15+ years in the field, but maybe they know better than me.

davidgl 9y ago

For anyone would missed it, also see this great link on HN recently: https://news.ycombinator.com/item?id=16233644 https://news.ycombinator.com/item?id=16233644 - DNA seen through the eyes of a coder (2017)