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How to sequence your DNA for <$2k

https://maxlangenkamp.substack.com/p/how-to-sequence-your-dna-for-2k
54•yichab0d•2h ago

Comments

pixelpoet•1h ago
> ‘Sequencing by synthesis’. instead of chopping up and separating each base pair through a gel lattice, we [cuts off]

k

> 200 µL of blood (about ⅕ of a ml)

"About"? Anyway, thanks for the clarification.

NuclearPM•36m ago
Maybe the “about” was supposed to cover the 200 µL as well.
7e•1h ago
Just wait for the Nebula Black Friday sale.
dunk010•1h ago
Nebula and Dante will do this for like $300, and you can get 30x coverage at every base or even 100x coverage if you pay a little more. The $1000 genome was here more than a decade ago.
sbassi•1h ago
yes, the difference here is that the $1000 tag is "at-scale price". You reach that price point by running multiple sequencing with a set of reactive.
zaptheimpaler•1h ago
I wanted to try this, but I looked into Nebula a bit more.

Nebula is facing a class action for apparently disclosing detailed genomic data to Meta, Microsoft & Google. The subreddit is also full of reports of people who never received their results years after sending their kits back. There are also concerns about the quality of sequencing and false positives in all DTC genomics testing. Given what happened with 23andme as well and all of this stuff, I'm wary of sending my genetic data to any private company.

Aurornis•1h ago
> There are also concerns about the quality of sequencing and false positives in all DTC genomics testing.

Even when the raw results are accurate there is a cottage industry of consultants and snake-oil sellers pushing bad science based on genetic testing results.

Outside of a few rare mutations, most people find their genetic testing results underwhelming or hard to interpret. Many of the SNPs come with mild correlations like “1.3X more likely to get this rare condition” which is extremely alarming to people who don’t understand that 1.3 times a very small number is still a very small number.

The worst are the consultants and websites that take your files and claim to interpret everything about your life or illness based on a couple SNPs. Usually it’s the famous MTHFR variants, most of which have no actual impact on your life because they’re so common. Yet there are numerous Facebook groups and subreddits telling you to spend $100 on some automated website or consultant who will tell you that your MTHFR and COMT SNPs explain everything about you and your ills, along with which supplements you need to take (through their personal branded supplement web shop or affiliate links, of course).

phyzome•1h ago
Yeah, the only way I would ever do DNA sequencing is anonymously...
mquander•6m ago
I was interested to read this because some time ago I had my genome sequenced by Nebula. If you look at the lawsuit you can see that what Nebula did was use off-the-shelf third-party analytics products on their website, including recording analytics pings when users buy a kit, and pings when users use the Nebula website to browse Nebula's high-level analysis of their traits (leaking that the user has those traits to the analytics provider.)

This behavior represents a contemptible lack of respect for users' privacy, but it's important to distinguish it from Nebula selling access to users' genomes.

https://www.classaction.org/media/portillov-nebula-genomics-...

freehorse•1h ago
Yeah but then basically somebody else gets ownership of your genetic data and gets the right to do anything with it in the context of their "legitimate interests". Not to mention to probability of that company getting hacked or sold, as it has already happened with some.
subroutine•28m ago
Does Nebula or Dante provide BAM or just VCF?
conradev•18m ago
Dante includes a BAM
Metacelsus•6m ago
Both do. I got mine through Dante, my wife through Nebula.
coppa•1h ago
Speaking of which I would advise : Svante Pääbo Neanderthal Man: In Search of Lost Genomes then even better imho The Naked Neanderthal by Ludovic Slimak. After these books I spent many hours listening to the full courses of Jean-Jacques Hublin, chaire Paléoanthropologie in college de France ( in french but probably translatable now with automatic features ?). This was an unexpected and wonderful path.
jasongill•1h ago
Unfortunately, the "MinION Starter Kit" for $1000 appears to no longer be available; the link in the article to the kit goes to a 404 page, and the cheapest MinION device with flow cells is now $4950 USD
jolmg•1h ago
Article was posted 2 days ago...
greazy•37m ago
The article author probably bought the starter kit a while ago. It might explain why the pore count was low. It's a biological product so it degrades over time.
Aurornis•1h ago
Interesting concept, but between the broken hardware and the way they gave up before getting anything useful this article was rather disappointing:

> Another problem was our flow cell was malfunctioning from the start — only 623 out of 2048 pores were working.

Is this normal for the machine? Is there a better write up somewhere where they didn’t give up immediately after one attempt?

sbassi•1h ago
it depends of the sample. usually you have at least 1200, with a guaranteed of at least 800, so maybe he could ask for a refund.
homeless_engi•46m ago
Hi, believe it or not, I have actually done what the authors were attempting. I used saliva rather than blood as a source of DNA and extracted it using a Qiagen kit.

My Nanopore flow cell had nearly every pore working from the start. So I would say that is not normal. Maybe it was stored incorrectly.

IceHegel•40m ago
Who can do this with good data controls? I don't want to have to dig through the fine print of some Terms of Service page to figure out if a sequencing company is going to save a copy of my genetic code for possible future use.
greazy•26m ago
I sequences my genome about 10 year's ago using illumina platform for ~1200AUD. We used a university sequencing facility. They were happy to extract and sequence the dna using a shotgun approach. Depth was 5x and I think we achieved about 90% coverage. It was just for fun.

The issue with this approach is that you'll receive raw data that needs to be processed. Even after processing you'll need to do further analysis to answer your questions. After all this, I'd be suspicious of the results and seek a medical councellor to discuss and perform further tests.

I'd advise on thinking what questions you want answered. 'Sequencing your genome' sounds amazing but imo you're better off with seeking accredited tests with acrionable results.

greazy•38m ago
The thermocycler replacement using an electric kettle is hilarious. Thats how old school dna amplification would happen before the invention of thermocyclers.

OP you'd get better results of you centrifuge your blood, extract the white blood cells and sequence those instead of whole blood. Thats a bit tricky with a lance and a tiny device though...

optionalsquid•27m ago
It's cool that nanopore technologies are getting this affordable, but keep in mind that these technologies (to my knowledge) still have very high error rates compared older sequencing techniques. Both in terms of individual nucleotides (A, C, G, and Ts) being misread, but also in terms of stretches of nucleotides being mistakenly added to or removed from the resulting sequences (indels).

So, yes, you can sequence your genome relatively cheaply using these technologies at home, but you won't be able to draw any conclusions from the results

greazy•19m ago
With the recent R10 flow cells the error rate has improved. The basecalling models have also been steadily improving and therefore reducing the error rate.

For assembling a bacterial genome the consensus error rate is as low or in some cases better than Illumina.

Nanopore platform has its usecases that Illumina falls short on.

> So, yes, you can sequence your genome relatively cheaply using these technologies at home, but you won't be able to draw any conclusions from the results

Agreed, any at home sequencing should not be used to draw any conclusions.

Ovah•18m ago
That's a prevalent misconception even in the scientific community. Sure, each read has 1% incorrect bases (0.01). But each segment of DNA is read many times over. More or less 0.01^(many times) ≈ 0 incorrect bases.
optionalsquid•8m ago
The author got less than 1x coverage for their efforts. To get the kind of coverage required for reliable base-calls, you need significantly higher coverage, and therefore a significantly higher spend
nashashmi•22m ago
If I have my genome dna data, where can I get it analyzed? For ancestry? For health info? Etc. of course With privacy!
isbvhodnvemrwvn•3m ago
Forget any use for ancestry with privacy guarantees. All you'll get is magic "ethnicity" percentages, kind of astrology of genealogy. For it to be useful in genealogy context you need to rely on matching and analyzing common ancestors, this will inherently lead to your data being shared in one way or another and possibly your identity being revealed.
teekert•12m ago
We are not “in the nanopore era of sequencing”. We are (still) firmly in the sequencing by synthesis era.

Yes it requires chopping the genome opening small(er) pieces (than with Nanopore sequencing) and then reconstructing the genome based on a reference (and this has its issues). But Nanopore sequencing is still far from perfect due to its high error rate. Any clinical sequencing is still done using sequencing by synthesis (at which Illumina has gotten very good over the past decade).

Nanopore devices are truly cool, small and comparatively cheap though, and you can compensate for the error rate by just sequence everything multiple times. I’m not too familiar with the economics of this approach though.

With sbs technology you could probably sequence your whole genome 30 times (a normal “coverage”) for below 1000€/$ with a reputable company. I’ve seen 180$, but not sure if I’d trust that.

Metacelsus•3m ago
>you can compensate for the error rate by just sequence everything multiple times.

Usually, but sometimes the errors are correlated.

Overall I agree, short read sequencing is a lot more cost effective. Doing an Illumina whole genome sequence for cell line quality control (at my startup) costs $260 in total.

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