Discussion summary

A discussion on home DNA sequencing highlights the importance of error correction, with some users sharing personal experiences and skepticism about its practical value.

What the discussion says

  • Error correction in sequencing is crucial, especially with low coverage.
  • Some users find the process dense but manageable with AI tools.
  • Skepticism exists about the practical benefits of personal genome data.
10x coverage genuinely washes out errors because they're closer to independent.
joel_liu
Uploading protocols to ChatGPT makes understanding easier.
bmwoolf

Comments

Hacker News

The "non-random errors" point buried a few replies down deserves to be the headline, not a footnote. With Illumina, 10x coverage genuinely washes out errors because they're closer to independent per-read noise. With Nanopore, errors cluster at specific motifs (homopolymers, certain k-mers) due to how the pore physically reads the strand — so the same systematic mistake shows up across most of your reads at that position, and naive majority-vote consensus won't fix it. You need a basecaller/consensus model trained to correct for those specific failure modes (which is exactly what the current-gen Guppy/Dorado models try to do), not just "more depth." That distinction matters a lot for a home setup: coverage is cheap, but knowing where your specific errors are systematic vs. random is what determines whether "buy more reads" actually gets you to clinical-grade accuracy or just gives you a very confident wrong answer.

by joel_liu

> This is intended to be read by AI

Fuck this

by bleepblap

Literally left the article to come here and say this.

by SuperSixFour

As long as the AI doesn't brush its teeth all good.

by hahahaa

Yeah that's weird. The instructions are not even hard to read. I don't understand what an LLM would add to this.

by asveikau

Hi, author here- you can read it too, though it is dense. I have updated that specific sentence.

I found it easier to upload the protocol to ChatGPT and have audio walk you through it. This allows you to swap between pipettes, measurements, etc without having to look at the screen, reducing context-switching

by bmwoolf

Man, doctors thought they had it bad before. For just a six yards I can play Peter Thiel at home! $6k invested so I can set an AI in YOLO mode to tell me I have some hyper-specific version of kennel cough?

“But that occurs in dogs?”

“You’re right. Let me look into actual gene sequencing instead of just guessing. I think the N is the load bearing letter.”

by tclancy

> The near-term value is turning a static genome into something queryable

Ok. So ... how exactly is this valuable?

If you realise "hey, I gots Huntington disease", this is going to make you feel better? Or any other incurable disease? I am not disputing that knowing the sequence is useless in general, mind you. I am specifically asking WHY it is necessary to know your genome sequence. This seems to be a simplification or just a "having reached a milestone". But then they don't really explain WHY it is useful. None of the bulletin points he listed is really useful:

> Which variants do I have?

And this is useful ... how exactly?

> Which genes and pathways are affected?

And ... this matters why?

> Which medicines might I metabolize differently?

Ok, so this has a potential use case here, since he can choose to avoid specific drugs. How useful that really is in practice is unclear. (Don't confuse drug companies trying to convince YOU that personalized medicine is important on THEIR use case.)

> What rare variants should I take seriously?

Seriously ... how? Ok, you avoid some compounds. Now what.

> Where does the model know nothing yet?

Great, so a model that is limited, but now I need to burden myself with having to know where that limitations are. So my brain just has extra processing to do, without getting anything useful in return.

> the “edit yourself with CRISPR” will most likely follow

Except that they have not solved the off-target cleavage yet. Besides, they milk the prices anyway. DNA manipulation should be safe, secure, correct and affordable. None of that is the case right now. They publish papers where CRISPR has solved everything, but then fail to explain why it isn't already used by billions. And there are reasons as to why.

> Give your genome to Claude Code

Oh my god ... AI becomes your dependency here.

Note that the step-by-step guide is actually not totally useless, as it can give a basis for real work. But I highly doubt that untrained people will easily be able to go through those steps. Everyone is a master in the lab now? RNA is easy to handle? Guess then one would have to explain why RNase A is used (ok ok it's not playing a huge role here since DNA is the target of isolation, but it is more of an example of how many things can go wrong, and there is not really an explanation of why xyz is used; this looks like an AI step-by-step guide. AI really makes people dumber).

by shevy-java

This feels like the acme of narcissism. How much time and money are people willing to spend on navel gazing?

by bambax

I don't get you at all.

Is going to your doctor or eating better food "navel gazing"? Predispositions to some diseases can be read from your DNA. Remember Angelina Jolie undergoing preventive mastectomy because she had a high genetic risk for breast cancer? Well, so do many non-celebrities.

Then there is the specific case of people who may suspect that their bio-parents are someone else, and there is nothing weird about wanting to know where you actually come from.

by inglor_cz

When you are taking care of your health, and need to learn more about your built-in limitations is it still narcissistic?

At the bottom of the page there is a link to Sid Sijbrandij's cancer journey. He is one of the cofounders of GitLab. This is one of the coverages of his story: https://centuryofbio.com/p/sid

by rtodea

That’s quite judgmental and shows an impressive lack of scientific curiosity.

by epgui

True story, I found a god damn tick in my navel yesterday. Sometimes a bit of navel gazing can be healthy, figuratively and literally.

On a reasonable level, navel gazing (the figurative kind) is maybe better called self-reflection. I use DNA for genealogy, and it seems to me from the people I meet, that many get a healthier approach to our identity once we learn more about our genetic background. Identity politics, collective identity building around ancestry - identity building of all kinds really - needs simple stories. And the stories DNA tell are never simple.

by vintermann

Can CRISPR also be done at home this cheaply?

Seems like maybe of the 3 dystopias: AI, Global Warming, Bio-warfare. That this is demonstrating that the home grown virus is closer than we think.

by FrustratedMonky

I am very impressed with the, why wait? just do it now approach to the future. which while not here, IS there.

by metalman

Nothing about this is the future. Sequencing at home will not solve any major problems. It's mainly a fun exercise to demonstrate that sequencing has been commodified.

by dekhn

Reminds me of the Gloing Plant Project. I never got my glowing flower but would have settled for the instruction manual, also never created :(

https://en.wikipedia.org/wiki/Glowing_Plant_project

By the by, can't seen to bring up the actual site linked on this post.

by SilentM68

You can get one here, you'll have to wait until next year though: https://light.bio/

by shellfishgene

I'm too afraid I would learn something awful about myself.

by TurdF3rguson

Unfortunately you’d have no power to correct it. Even if such a thing were possible. I hope that changes.

by peyton

That's unlikely, but I do think that the health benefits of full sequence testing yourself are largely hypothetical at this point anyway. Unless you're a competitive athlete maybe?

It's genealogy it's useful for. But genealogy, it's really useful for.

by vintermann

one main marketing leverage of 23andMe, AncestryDNA, etc are fulfilling the curiosity of people who want to know which part of the world their genes are from. I guess that dataset should be preparatory.

by armanj

Problem with those providers - they only check 700K positions out of 3 billion and there is no mapping quality or allelic depth data in those dataset and this is critical for assessing whether the detected variant is a false positive or real.

It's not suitable for health investigations since most of DNA is not sequenced and genotyping technology is known to produce high rate of false positive for rare mutations.

(I'm the solo-founder of Gene Inspector Pro, mentioned in the blog post). AMA. :)

by sergey-a

If the sequencer was 10x cheaper then I might do it.

by giantg2

With such cheap costs every city should be sequencing dog turds and sending out big fines. The pay back would be very quick.

by brikym

It's quite a bit more difficult with poop. A rather large proportion of the DNA in poop isn't from the creature that pooped it. (mostly bacteria)

by colechristensen

I think cameras or even just a reporting hotline would be easier. The problem is lack of motivation I think rather than a money thing.

by podocarp

What is the accuracy in this ? Aka if I run the experiment 10 times how many differences will i get? I don’t have a physical sense on what would be a good number.

by whatever1

Oxford Nanopore unfortunately has a high error rate (3-5%) compared to other sequencing technologies. And the errors are non-random

by Jules-Bertholet

Join the discussion

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  • Hacker News
  • The "non-random errors" point buried a few replies down deserves to be the headline, not a footnote. With Illumina, 10x coverage genuinely washes out errors because they're closer to independent per-read noise. With Nanopore, errors cluster at specific motifs (homopolymers, certain k-mers) due to how the pore physically reads the strand — so the same systematic mistake shows up across most of your reads at that position, and naive majority-vote consensus won't fix it. You need a basecaller/consensus model trained to correct for those specific failure modes (which is exactly what the current-gen Guppy/Dorado models try to do), not just "more depth." That distinction matters a lot for a home setup: coverage is cheap, but knowing where your specific errors are systematic vs. random is what determines whether "buy more reads" actually gets you to clinical-grade accuracy or just gives you a very confident wrong answer.
    by joel_liu
  • > This is intended to be read by AI

    Fuck this

    by bleepblap
  • Literally left the article to come here and say this.
    by SuperSixFour
  • As long as the AI doesn't brush its teeth all good.
    by hahahaa
  • Yeah that's weird. The instructions are not even hard to read. I don't understand what an LLM would add to this.
    by asveikau
  • Hi, author here- you can read it too, though it is dense. I have updated that specific sentence.

    I found it easier to upload the protocol to ChatGPT and have audio walk you through it. This allows you to swap between pipettes, measurements, etc without having to look at the screen, reducing context-switching

    by bmwoolf
  • Man, doctors thought they had it bad before. For just a six yards I can play Peter Thiel at home! $6k invested so I can set an AI in YOLO mode to tell me I have some hyper-specific version of kennel cough?

    “But that occurs in dogs?”

    “You’re right. Let me look into actual gene sequencing instead of just guessing. I think the N is the load bearing letter.”

    by tclancy
  • > The near-term value is turning a static genome into something queryable

    Ok. So ... how exactly is this valuable?

    If you realise "hey, I gots Huntington disease", this is going to make you feel better? Or any other incurable disease? I am not disputing that knowing the sequence is useless in general, mind you. I am specifically asking WHY it is necessary to know your genome sequence. This seems to be a simplification or just a "having reached a milestone". But then they don't really explain WHY it is useful. None of the bulletin points he listed is really useful:

    > Which variants do I have?

    And this is useful ... how exactly?

    > Which genes and pathways are affected?

    And ... this matters why?

    > Which medicines might I metabolize differently?

    Ok, so this has a potential use case here, since he can choose to avoid specific drugs. How useful that really is in practice is unclear. (Don't confuse drug companies trying to convince YOU that personalized medicine is important on THEIR use case.)

    > What rare variants should I take seriously?

    Seriously ... how? Ok, you avoid some compounds. Now what.

    > Where does the model know nothing yet?

    Great, so a model that is limited, but now I need to burden myself with having to know where that limitations are. So my brain just has extra processing to do, without getting anything useful in return.

    > the “edit yourself with CRISPR” will most likely follow

    Except that they have not solved the off-target cleavage yet. Besides, they milk the prices anyway. DNA manipulation should be safe, secure, correct and affordable. None of that is the case right now. They publish papers where CRISPR has solved everything, but then fail to explain why it isn't already used by billions. And there are reasons as to why.

    > Give your genome to Claude Code

    Oh my god ... AI becomes your dependency here.

    Note that the step-by-step guide is actually not totally useless, as it can give a basis for real work. But I highly doubt that untrained people will easily be able to go through those steps. Everyone is a master in the lab now? RNA is easy to handle? Guess then one would have to explain why RNase A is used (ok ok it's not playing a huge role here since DNA is the target of isolation, but it is more of an example of how many things can go wrong, and there is not really an explanation of why xyz is used; this looks like an AI step-by-step guide. AI really makes people dumber).

    by shevy-java
  • This feels like the acme of narcissism. How much time and money are people willing to spend on navel gazing?
    by bambax
  • I don't get you at all.

    Is going to your doctor or eating better food "navel gazing"? Predispositions to some diseases can be read from your DNA. Remember Angelina Jolie undergoing preventive mastectomy because she had a high genetic risk for breast cancer? Well, so do many non-celebrities.

    Then there is the specific case of people who may suspect that their bio-parents are someone else, and there is nothing weird about wanting to know where you actually come from.

    by inglor_cz
  • When you are taking care of your health, and need to learn more about your built-in limitations is it still narcissistic?

    At the bottom of the page there is a link to Sid Sijbrandij's cancer journey. He is one of the cofounders of GitLab. This is one of the coverages of his story: https://centuryofbio.com/p/sid

    by rtodea
  • That’s quite judgmental and shows an impressive lack of scientific curiosity.
    by epgui
  • True story, I found a god damn tick in my navel yesterday. Sometimes a bit of navel gazing can be healthy, figuratively and literally.

    On a reasonable level, navel gazing (the figurative kind) is maybe better called self-reflection. I use DNA for genealogy, and it seems to me from the people I meet, that many get a healthier approach to our identity once we learn more about our genetic background. Identity politics, collective identity building around ancestry - identity building of all kinds really - needs simple stories. And the stories DNA tell are never simple.

    by vintermann
  • Can CRISPR also be done at home this cheaply?

    Seems like maybe of the 3 dystopias: AI, Global Warming, Bio-warfare. That this is demonstrating that the home grown virus is closer than we think.

    by FrustratedMonky
  • by RobotToaster
  • I am very impressed with the, why wait? just do it now approach to the future. which while not here, IS there.
    by metalman
  • Nothing about this is the future. Sequencing at home will not solve any major problems. It's mainly a fun exercise to demonstrate that sequencing has been commodified.
    by dekhn
  • Reminds me of the Gloing Plant Project. I never got my glowing flower but would have settled for the instruction manual, also never created :(

    https://en.wikipedia.org/wiki/Glowing_Plant_project

    By the by, can't seen to bring up the actual site linked on this post.

    by SilentM68
  • You can get one here, you'll have to wait until next year though: https://light.bio/
    by shellfishgene
  • I'm too afraid I would learn something awful about myself.
    by TurdF3rguson
  • Unfortunately you’d have no power to correct it. Even if such a thing were possible. I hope that changes.
    by peyton
  • That's unlikely, but I do think that the health benefits of full sequence testing yourself are largely hypothetical at this point anyway. Unless you're a competitive athlete maybe?

    It's genealogy it's useful for. But genealogy, it's really useful for.

    by vintermann
  • one main marketing leverage of 23andMe, AncestryDNA, etc are fulfilling the curiosity of people who want to know which part of the world their genes are from. I guess that dataset should be preparatory.
    by armanj
  • Problem with those providers - they only check 700K positions out of 3 billion and there is no mapping quality or allelic depth data in those dataset and this is critical for assessing whether the detected variant is a false positive or real.

    It's not suitable for health investigations since most of DNA is not sequenced and genotyping technology is known to produce high rate of false positive for rare mutations.

    (I'm the solo-founder of Gene Inspector Pro, mentioned in the blog post). AMA. :)

    by sergey-a
  • If the sequencer was 10x cheaper then I might do it.
    by giantg2
  • With such cheap costs every city should be sequencing dog turds and sending out big fines. The pay back would be very quick.
    by brikym
  • It's quite a bit more difficult with poop. A rather large proportion of the DNA in poop isn't from the creature that pooped it. (mostly bacteria)
    by colechristensen
  • I think cameras or even just a reporting hotline would be easier. The problem is lack of motivation I think rather than a money thing.
    by podocarp
  • What is the accuracy in this ? Aka if I run the experiment 10 times how many differences will i get? I don’t have a physical sense on what would be a good number.
    by whatever1
  • Oxford Nanopore unfortunately has a high error rate (3-5%) compared to other sequencing technologies. And the errors are non-random
    by Jules-Bertholet

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