9 ms·

How to sequence your DNA for <$2k

252 points by yichab0d 1y ago

pixelpoet 1y 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 1y ago
  Maybe the “about” was supposed to cover the 200 µL as well.
7e 1y ago
Just wait for the Nebula Black Friday sale.
dunk010 1y 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 1y 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 1y 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 1y 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 1y ago
    Yeah, the only way I would ever do DNA sequencing is anonymously...
    - deleted 1y ago
      [deleted]
    - jjallen 1y ago
      Because of public family trees potentially linking a genome to a family, no dna is fully anonymous these days.
      - phyzome 1y ago
        The DNA itself is not "anonymous", but I would do it without giving my real name, address, etc. They could know who the DNA is related to, but not gain more information than that. Even better would be to swap identity with someone else who wants to get sequenced...
- freehorse 1y 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 1y ago
  Does Nebula or Dante provide BAM or just VCF?
  - conradev 1y ago
    Dante includes a BAM
  - Metacelsus 1y ago
    Both do. I got mine through Dante, my wife through Nebula.
- sroussey 1y ago
  What about sequencing.com?
- otherme123 1y ago
  Note the $2,000 bill includes the DNA extraction machinery and the sequencer itself. The sequencers that Nebula et al use are probably over 1 million $. If you want to go even cheaper and depending of what you want, you can go for an exome instead of a WGS. And a lot of people are sequencing when they really want genotyping. But I would not be surprised if someone is already getting $100 WGS.
- stared 1y ago
  I see 399EUR (or $466) for the cheapest variant https://www.dantelabs.com/products/whole-genome-sequencing https://www.dantelabs.com/products/whole-genome-sequencing - or do I miss anything?
coppa 1y 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 1y 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 1y ago
  Article was posted 2 days ago...
  - greazy 1y 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.
  - numpad0 1y ago
    These are by no means a new product. I think the early prototypes for these possibly predate the microUSB plug. 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.
    - bonsai_spool 1y ago
      > The brochures always showed it next to a completely non-sterile laptop 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.
Aurornis 1y 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 1y 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 1y 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.
  - LolWolf 1y ago
    Do you have a write up somewhere? If not, it would be amazing if you wrote one! 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.)
    - homeless_engi 1y ago
      Thanks for the kind words! I have not written it up but would like to. A word of warning: by trying to get into sequencing, I eventually burned through ~20k USD of student loans (still unpaid) with little to show. Nanopore sequencing also requires some specialized equipment (at least a micro centrifuge and micropipette and possibly more) which is not cheap.
      - 1y ago
IceHegel 1y 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 1y 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.
  - otherme123 1y ago
    The really difficult part of sequencing is after the Vcf. Before that is trivial, you can plug your fastq raw data in some Nextflow pipelines and in a couple of days of computing get plenty of "results" to be busy exploring for years.
greazy 1y 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...
- jszymborski 1y ago
  When I was in school in the early 2010s (maybe 17-18yo) our intro to biology course had us thermocycle by alternating between warm tubs of water with the use of an egg-timer. When I later used a thermocycler during my research career I really came to appreciate the little bugger (even though it caused a lot of headaches anyway)
  - zorgster 1y ago
    Now you can buy a portable thermocycler with 13k rpm centrifuge all-in-one with gel electrophoresis - BentoLab for £1299 in UK. Carry case £54. (They sell a Dipstick DNA Extraction kit for £38.50, pipettes, and mastermix...) A portable lab with a thermocycler, 13k rpm centrifuge, and gel electrophoresis https://bento.bio/bento-lab/ https://bento.bio/bento-lab/
- yichab0d 1y ago
  we did centrifuge :) using the zymo purification kit
optionalsquid 1y 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 1y 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 1y 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 1y 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
  - bonsai_spool 1y 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. That's true in targeted sequencing, but when you try to sequence a whole genome, this is unlikely.
nashashmi 1y 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 1y 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.
- Real_S 1y ago
  Take a look at Monadic DNA: https://monadicdna.com/ https://monadicdna.com/ 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: https://news.ycombinator.com/submitted?id=vishakh82 https://news.ycombinator.com/submitted?id=vishakh82
- cariaso 1y ago
  https://patientuser.com https://patientuser.com
teekert 1y 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.
- Danjoe4 1y ago
  Nanopore is good for hybrid sequencing. You can align the higher quality illumina reads against its longer contiguous reads
- Metacelsus 1y 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.
- bonsai_spool 1y ago
  > 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). 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.
jaberjaber23 1y ago
Nanopore’s getting closer
FL33TW00D 1y ago
Dante and Nebula have a bad reputation. ySeq has an 8 month wait list. This guys Nanopore sequencer doesn’t work. It is quite hard to get yourself sequenced in EU in 2025.
- zorgster 1y ago
  tellmeGen have begun to offer it in Spain... 30X for £269 with 10% discount on now with coupon HALLOWEEN10 until Nov 4th. https://shop.tellmegen.com/en/collections/ultra https://shop.tellmegen.com/en/collections/ultra
shevy-java 1y ago
Wasn't the cost a few years ago below 1000 already?
arjie 1y ago
I used Nebula (seems to be rebranded and more expensive now) for my wife and me, and for my parents and brother, and it was pretty straightforward. I paid for the 'lifetime' plan but they removed it before we did it for anyone else and it was pretty reasonable. I downloaded the FASTQ files and stuck it in an R2 bucket for myself. Nebula cost about $250 and there's a monthly $50 or something plan that's compulsory but you can cancel it right away. If you're curious about my genome, here are my VCF files https://my.pgp-hms.org/profile/hu81A8CC 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 Put that into an LLM or look it up here https://www.snpedia.com/index.php/Rs104894396 https://www.snpedia.com/index.php/Rs104894396 to find out which pathogenic mutation I am heterozygous for. 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.
- dash2 1y ago
  The obvious question: why are you so relaxed about revealing your whole DNA to the world?
deleted 1y ago
[deleted]
kyriakos 1y ago
What is the practical use of having your dna sequenced?
- cmrx64 1y ago
  it revealed I am comparatively insensitive to Ritalin and guided ADHD medication choices
  - bradydjohnson 1y ago
    Did you learn this from Genomind? Or how did you get from genomes to useful information re: meds?
ml_basics 1y ago
The graph at the beginning showing the cost of sequencing over time falling faster than Moore's law stops in 2015. Would love to see how things have progressed since then. Casually googling i only saw plots up to 2021 but looks to me like progress is now slower than Moore's law since ~2015. Maybe things will change when Nanopore gets more reliable
- dust42 1y ago
  The graph also only starts in 2001. I worked as a student at the EMBL (European Molecular Biology Laboratory) in the bio-physics instrumentation group in the mid 90ies. The lab group was developing prototypes of thin-film electrophoresis DNA sequencers. Pharmacia Biotech then bought some of the tech and brought it to market. AFAIR at that time it were some of the fastest sequencers but we are talking of low 100s of base pairs per day.
- mfld 1y ago
  The NHGRI updated these plots for years. Sad to see that there is no update since 2022, presumably due to lack of funding. The sub-$100 genomes could be in reach within the next 5 years, from what I have seen.
iafiaf 1y ago
These guys didn't do their homework correctly. Keeping aside commercial vendors; their own garage setup for doomed to fail with their coverage (or lack thereof). Garbage in, garbage out.
justinc8687 1y ago
So given the mostly negative comments in this thread about various companies, can anyone recommend a reasonably priced, reasonably quick, place to get your DNA sequenced and subsequently analyzed? I'm curious about a more general view as well as some specific mutations. Any recommendations?
savrajsingh 1y ago
Check out https://mynucleus.com https://mynucleus.com -- we do whole-genome DNA sequencing from a cheek swab for about $500 (use code savraj10 for 10% off), so no blood drawn as in this example. We also give you your risks for over 2k diseases and, if your partner does the test, predict outcomes for your future kids. Alexis is one of our investors and we have a big announcement coming next week! We also allow download of all raw data and are SOC2 + HIPAA compliant.
- ramraj07 1y ago
  What coverage does your sequencing provide?
- logtrees 1y ago
  Amazing. I remember when something like this was a massive cost, if even accessible to the layperson. Now it's ~$500? Godspeed.
- arresin 1y ago
  Do you accept monero?
- aquafox 1y ago
  The problem for me is not getting my DNA sequenced but not having to trust a third party with my genetic information. As wirtten in the article, they only achieved a 13% coverage (even less if because you have to assume that not all base calls are correct), which is not useful for any sort of genetic analysis. So the title is really misleading.
- cmcaleer 1y ago
  What’s stopping a similar crisis that 23andMe customers faced where their genetic data along with their identifying information getting sold to the highest bidder if you ever become insolvent? Considering how big a deal that was at the time, and how strong a differentiator it would be, it’s notable how absent from the homepage. It’s nice that Nucleus claims not to sell the data, but 23andMe had similar claims, it wasn’t strong enough to prevent genetic data from being transferred if they were to be acquired. This has always been something I’ve been interested in but so far no company handles privacy concerns of data that’s so deeply fundamentally personal and private in a satisfactory way, and I’m especially apprehensive post-23andMe. Taking a dice roll on Nucleus not just pulling another 23andMe seems not worth the ~$3000 saving you claim to be offering.
ramraj07 1y ago
Unless you are buying a machine, making sure its offline and doing it all by yourself, DONT sequence your DNA! You're not just condemning your genetic data to whoever might pay to obtain it but that of all your future progeny and even that of all your blood relatives. Its insane how bad the worst case scenario is.
- literalAardvark 1y ago
  And it also doesn't help you with anything. It has near zero predictive power about your health unless combined with epigenetic data, which you can't get. It might even make you sicker through anxiety or other nocebo. It's only really useful as a confirmation for a doctor's diagnosis, and those are done with slightly better data controls.
zanter 1y ago
[dead]

252 points by yichab0d 1y 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 1y ago
Maybe the “about” was supposed to cover the 200 µL as well.

7e 1y ago

Just wait for the Nebula Black Friday sale.

dunk010 1y 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 1y 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 1y 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 1y 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 1y ago
  Yeah, the only way I would ever do DNA sequencing is anonymously...
  - deleted 1y ago
    [deleted]
  - jjallen 1y ago
    Because of public family trees potentially linking a genome to a family, no dna is fully anonymous these days.
    - phyzome 1y ago
      The DNA itself is not "anonymous", but I would do it without giving my real name, address, etc. They could know who the DNA is related to, but not gain more information than that. Even better would be to swap identity with someone else who wants to get sequenced...
freehorse 1y 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 1y ago
Does Nebula or Dante provide BAM or just VCF?
- conradev 1y ago
  Dante includes a BAM
- Metacelsus 1y ago
  Both do. I got mine through Dante, my wife through Nebula.
sroussey 1y ago
What about sequencing.com?
otherme123 1y ago
Note the $2,000 bill includes the DNA extraction machinery and the sequencer itself. The sequencers that Nebula et al use are probably over 1 million $. If you want to go even cheaper and depending of what you want, you can go for an exome instead of a WGS. And a lot of people are sequencing when they really want genotyping. But I would not be surprised if someone is already getting $100 WGS.
stared 1y ago
I see 399EUR (or $466) for the cheapest variant https://www.dantelabs.com/products/whole-genome-sequencing https://www.dantelabs.com/products/whole-genome-sequencing - or do I miss anything?

coppa 1y 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 1y 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 1y ago
Article was posted 2 days ago...
- greazy 1y 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.
- numpad0 1y ago
  These are by no means a new product. I think the early prototypes for these possibly predate the microUSB plug. 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.
  - bonsai_spool 1y ago
    > The brochures always showed it next to a completely non-sterile laptop 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.

Aurornis 1y 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 1y 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 1y 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.
- LolWolf 1y ago
  Do you have a write up somewhere? If not, it would be amazing if you wrote one! 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.)
  - homeless_engi 1y ago
    Thanks for the kind words! I have not written it up but would like to. A word of warning: by trying to get into sequencing, I eventually burned through ~20k USD of student loans (still unpaid) with little to show. Nanopore sequencing also requires some specialized equipment (at least a micro centrifuge and micropipette and possibly more) which is not cheap.
    - 1y ago

IceHegel 1y 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 1y 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.
- otherme123 1y ago
  The really difficult part of sequencing is after the Vcf. Before that is trivial, you can plug your fastq raw data in some Nextflow pipelines and in a couple of days of computing get plenty of "results" to be busy exploring for years.

greazy 1y 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...

jszymborski 1y ago
When I was in school in the early 2010s (maybe 17-18yo) our intro to biology course had us thermocycle by alternating between warm tubs of water with the use of an egg-timer. When I later used a thermocycler during my research career I really came to appreciate the little bugger (even though it caused a lot of headaches anyway)
- zorgster 1y ago
  Now you can buy a portable thermocycler with 13k rpm centrifuge all-in-one with gel electrophoresis - BentoLab for £1299 in UK. Carry case £54. (They sell a Dipstick DNA Extraction kit for £38.50, pipettes, and mastermix...) A portable lab with a thermocycler, 13k rpm centrifuge, and gel electrophoresis https://bento.bio/bento-lab/ https://bento.bio/bento-lab/
yichab0d 1y ago
we did centrifuge :) using the zymo purification kit

optionalsquid 1y 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 1y 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 1y 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 1y 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
- bonsai_spool 1y 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. That's true in targeted sequencing, but when you try to sequence a whole genome, this is unlikely.

nashashmi 1y 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 1y 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.
Real_S 1y ago
Take a look at Monadic DNA: https://monadicdna.com/ https://monadicdna.com/ 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: https://news.ycombinator.com/submitted?id=vishakh82 https://news.ycombinator.com/submitted?id=vishakh82
cariaso 1y ago
https://patientuser.com https://patientuser.com

teekert 1y 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.

Danjoe4 1y ago
Nanopore is good for hybrid sequencing. You can align the higher quality illumina reads against its longer contiguous reads
Metacelsus 1y 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.
bonsai_spool 1y ago
> 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). 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.

jaberjaber23 1y ago

Nanopore’s getting closer

FL33TW00D 1y ago

Dante and Nebula have a bad reputation. ySeq has an 8 month wait list. This guys Nanopore sequencer doesn’t work. It is quite hard to get yourself sequenced in EU in 2025.

zorgster 1y ago
tellmeGen have begun to offer it in Spain... 30X for £269 with 10% discount on now with coupon HALLOWEEN10 until Nov 4th. https://shop.tellmegen.com/en/collections/ultra https://shop.tellmegen.com/en/collections/ultra

shevy-java 1y ago

Wasn't the cost a few years ago below 1000 already?

arjie 1y ago

I used Nebula (seems to be rebranded and more expensive now) for my wife and me, and for my parents and brother, and it was pretty straightforward. I paid for the 'lifetime' plan but they removed it before we did it for anyone else and it was pretty reasonable. I downloaded the FASTQ files and stuck it in an R2 bucket for myself. Nebula cost about $250 and there's a monthly $50 or something plan that's compulsory but you can cancel it right away. If you're curious about my genome, here are my VCF files https://my.pgp-hms.org/profile/hu81A8CC 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 Put that into an LLM or look it up here https://www.snpedia.com/index.php/Rs104894396 https://www.snpedia.com/index.php/Rs104894396 to find out which pathogenic mutation I am heterozygous for. 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.

dash2 1y ago
The obvious question: why are you so relaxed about revealing your whole DNA to the world?

deleted 1y ago

[deleted]

kyriakos 1y ago

What is the practical use of having your dna sequenced?

cmrx64 1y ago
it revealed I am comparatively insensitive to Ritalin and guided ADHD medication choices
- bradydjohnson 1y ago
  Did you learn this from Genomind? Or how did you get from genomes to useful information re: meds?

ml_basics 1y ago

The graph at the beginning showing the cost of sequencing over time falling faster than Moore's law stops in 2015. Would love to see how things have progressed since then. Casually googling i only saw plots up to 2021 but looks to me like progress is now slower than Moore's law since ~2015. Maybe things will change when Nanopore gets more reliable

dust42 1y ago
The graph also only starts in 2001. I worked as a student at the EMBL (European Molecular Biology Laboratory) in the bio-physics instrumentation group in the mid 90ies. The lab group was developing prototypes of thin-film electrophoresis DNA sequencers. Pharmacia Biotech then bought some of the tech and brought it to market. AFAIR at that time it were some of the fastest sequencers but we are talking of low 100s of base pairs per day.
mfld 1y ago
The NHGRI updated these plots for years. Sad to see that there is no update since 2022, presumably due to lack of funding. The sub-$100 genomes could be in reach within the next 5 years, from what I have seen.

iafiaf 1y ago

These guys didn't do their homework correctly. Keeping aside commercial vendors; their own garage setup for doomed to fail with their coverage (or lack thereof). Garbage in, garbage out.

justinc8687 1y ago

So given the mostly negative comments in this thread about various companies, can anyone recommend a reasonably priced, reasonably quick, place to get your DNA sequenced and subsequently analyzed? I'm curious about a more general view as well as some specific mutations. Any recommendations?

savrajsingh 1y ago

Check out https://mynucleus.com https://mynucleus.com -- we do whole-genome DNA sequencing from a cheek swab for about $500 (use code savraj10 for 10% off), so no blood drawn as in this example. We also give you your risks for over 2k diseases and, if your partner does the test, predict outcomes for your future kids. Alexis is one of our investors and we have a big announcement coming next week! We also allow download of all raw data and are SOC2 + HIPAA compliant.

ramraj07 1y ago
What coverage does your sequencing provide?
logtrees 1y ago
Amazing. I remember when something like this was a massive cost, if even accessible to the layperson. Now it's ~$500? Godspeed.
arresin 1y ago
Do you accept monero?
aquafox 1y ago
The problem for me is not getting my DNA sequenced but not having to trust a third party with my genetic information. As wirtten in the article, they only achieved a 13% coverage (even less if because you have to assume that not all base calls are correct), which is not useful for any sort of genetic analysis. So the title is really misleading.
cmcaleer 1y ago
What’s stopping a similar crisis that 23andMe customers faced where their genetic data along with their identifying information getting sold to the highest bidder if you ever become insolvent? Considering how big a deal that was at the time, and how strong a differentiator it would be, it’s notable how absent from the homepage. It’s nice that Nucleus claims not to sell the data, but 23andMe had similar claims, it wasn’t strong enough to prevent genetic data from being transferred if they were to be acquired. This has always been something I’ve been interested in but so far no company handles privacy concerns of data that’s so deeply fundamentally personal and private in a satisfactory way, and I’m especially apprehensive post-23andMe. Taking a dice roll on Nucleus not just pulling another 23andMe seems not worth the ~$3000 saving you claim to be offering.

ramraj07 1y ago

Unless you are buying a machine, making sure its offline and doing it all by yourself, DONT sequence your DNA! You're not just condemning your genetic data to whoever might pay to obtain it but that of all your future progeny and even that of all your blood relatives. Its insane how bad the worst case scenario is.

literalAardvark 1y ago
And it also doesn't help you with anything. It has near zero predictive power about your health unless combined with epigenetic data, which you can't get. It might even make you sicker through anxiety or other nocebo. It's only really useful as a confirmation for a doctor's diagnosis, and those are done with slightly better data controls.

zanter 1y ago

[dead]