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.
There is no reason for Nanopore to supplant sequencing-by-synthesis for short reads - that's largely solved and getting cheaper all the while.
The future clinical utility will be in medium- and large-scale variation. We don't understand this in the clinical setting nearly as well as we understand SNPs. So Nanopore is being used in the research setting and to diagnose individuals with very rare genetic disorders.
(edit)
> We are not “in the nanopore era of sequencing”. We are (still) firmly in the sequencing by synthesis era.
I also strongly disagree.
SBS is very reliable but it's common (if Toyota is the most popular car, does that mean we're in the Toyota internal combustion era? Or can Waymo still matter despite its small footprint?).
Novelty in sequencing is coming from ML approaches, RNA-DNA analysis, and combining long- and short-read technologies.
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.
It would be difficult to break a modest program into basic blocks and then reconstruct it. Same with paragraphs in a book.
How does this work with DNA?
> 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?
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.
I was planning on doing a similar thing (also with saliva) once I finished moving in and had a bit more time after conferences. (But, of course, I’d have to go through and actually figure out all of the mechanics and so on.)
No, it's not "normal," but it is fairly common. When I worked in NGS, nearly 1/4 of flow cells were duds. ONT used to have a policy where you could return the cell and get a new one if it failed its self-test.
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.
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-...
I don't have any evidence they're selling anything but that lawsuit shows pretty sloppy behaviour for a company that should be thinking very deeply about privacy. I guess that's about what you said though :)
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).
The brochures always showed it next to a completely non-sterile laptop, but it never made sense. It's fundamentally a bio lab equipment, just small. You probably should be wiping the package with disinfectant, use DNA-cides as needed, or follow whatever bioscience people consider the basic common sense hygiene standards.
This can be done in the field (read near a lot of dirt). This does not require sterility at all. The main problems with this are keeping your prep clean (which is different from sterile; primarily involves not getting bubbles where they shouldn't be etc.) and temperature/salt handling.
> These are by no means a new product. I think the early prototypes for these possibly predate the microUSB plug. > You probably should be wiping the package with disinfectant, use DNA-cides as needed, or follow whatever bioscience people consider the basic common sense hygiene standards.
The consumable product is what needs to be stored carefully. Its delivered DNA-free; no disinfectant is needed. It's actually hard for accidental DNA to be introduced at the sequencing step; that would usually reflect poor practices earlier on.
If you're curious about my genome, here are my VCF files https://my.pgp-hms.org/profile/hu81A8CC
If you want to indulge your curiosity some more:
$ rg "20189511" /Users/george/tmp/genome/nebula_roshan_NG1AW8W7PU.mm2.sortdup.bqsr.hc.vcf
3499829:chr13 20189511 rs104894396 C T 252.77 . AC=1;AF=0.500;AN=2;BaseQRankSum=1.54;ClippingRankSum=0.00;DB;DP=25;ExcessHet=3.0103;FS=4.008;MLEAC=1;MLEAF=0.500;MQ=60.00;MQRankSum=0.00;QD=10.11;ReadPosRankSum=0.666;SOR=0.160 GT:AD:DP:GQ:PL 0/1:15,10:25:99:281,0,436
In practice, when my wife and I did carrier screening we didn't do it with Nebula, but carrier screening also confirmed that we had GJB2-related hearing loss genes in common. The embryos of our prospective children were also sequenced so that we could have a child without the condition.
Anyway, if you'd like a test file of a real human to play with, there's mine (from Nebula) for you to take a look at. If you use an LLM you can have some fun looking at this stuff (you can see I'm a man because there are chrY variants in there).
I also used Dante because I wanted to compare the results of their sequencing and variant calling. Unfortunately, they have a different way to tie the sequence back to the user (you take the code they have and keep it safe, nebula has you put the stuff in a labeled container so it's already mapped by them) and I was in a hurry with other stuff. They never responded to me with any assistance on the subject - not even to refuse the request to get the code for that address - so I have no idea how they work.
The nanopore stuff is very cool, but I heard (on Twitter) there were quality control issues with the devices. I'd love to try it some time later just to line it up with my daughter's genome.
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...
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
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.
That's true in targeted sequencing, but when you try to sequence a whole genome, this is unlikely.
Whole-genome shotgun sequencing is pretty cheap these days.
The person you are replying to doesn't give any specific numbers, but in my experience, you aim for 5-20x average coverage for population level studies, depending on the number of samples and what you are looking for, and 30x or higher for studies where individuals are important.
For context, coverage refers to the (average) number of resulting DNA sequences that cover a given position in the target genome. Though there is of course variation in local coverage, regardless of your average coverage, and that can result in individual base-calls being being more or less reliable
You need multiple flow cells or a higher capacity flow cell to get anything close to 1X on an unselected genome prep.
Shotgun sequencing isn’t probably what you meant to say - this is all enzymatic or, if it’s sonicated, gets size selected.
But if we are talking nanopore sequencing, then yes, you need multiple flowcells. Which is not a problem if you are not a private person attempting to sequence your own genome on the cheap
You can do nanopore PCR/cDNA workflows right up to the largest known mRNAs (13kb).
Edit:
I’m not sure if you’re saying that you can’t do a 5/20/30X genome on nanopore - that’s also not true. It only makes sense in particular research settings, of course.
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.
It is quite hard to get yourself sequenced in EU in 2025.
They are building Fully Homomorphic Encryption (FHE) and Multiparty Computation (MPC) tools for genetic data. Your data format may need to be modified. They currently focus on the SNP results from places like Ancestry.
Some HN posts from their CEO:
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> 200 µL of blood (about ⅕ of a ml)
"About"? Anyway, thanks for the clarification.