7 ms·

How to sequence your genome at home

184 points by sprague 5y ago

colordrops 5y ago
I've been wary about submitting my DNA to a company so this is very intriguing. Is there enough data and/or a community and open software to support things like ancestry and disease profiles locally?
- amelius 5y ago
  Good question. I'm always afraid most of the useful medical data will be kept secret by these giant corporations, but let's hope this is not already the case.
- searine 5y ago
  Most of bioinformatics/computational biology is open source and so are most of the data sets. The companies that do this definitely have a 'special sauce' for ancestry, but most all of the disease annotations are public (see dbSNP). As for the paranoia about DNA companies, you are an anonymous drop in the ocean of sequenced DNA. There are laws against using it to inform insurance coverage. Sequencing yourself at one these companies and opting in for use in research is actually really important to collecting the sample sizes necessary to discover new causative variants for disease.
- teachingassist 5y ago
  It's tricky to organise, but in theory, yes, you can interpret your own results. Ancestry/23andme-type medical results are (in my opinion) almost entirely a nice write-up and display of public databases of research on SNPs, e.g. https://www.ncbi.nlm.nih.gov/snp/docs/entrez_help/ https://www.ncbi.nlm.nih.gov/snp/docs/entrez_help/, https://www.snpedia.com/ https://www.snpedia.com/ You could (for example) submit the data you get to Promethease which will do the processing for you. Promethease is now owned by MyHeritage, so I'm not sure how their terms are looking - I'd be a little cautious about using that.
- caymanjim 5y ago
  I've been curious about what my DNA says, and went so far as to buy a 23andme kit years ago. I never sent it in, because I don't like the idea of some company retaining that kind of deeply personal data about me. It's useless to resist, though; my sister and some cousins submitted theirs, and that's enough to destroy any real sense of anonymity I might have. I don't have any particular concern; it's just one of the myriad ways that privacy no longer exists.
  - weaksauce 5y ago
    > I don't have any particular concern we don't have even the slightest idea of where it could go right now. look 30 years ago and DNA wasn't a thing that people were worried about and now it's catching sloppy criminals. the technology opens up new, unexpected opportunities
    - adenadel 5y ago
      I get your point, but your timeline is pretty far off. The first human gene therapy happened in 1990 so DNA has been a thing for awhile.
      - Retric 5y ago
        The first use of DNA in a criminal case only goes back to 1987. As such 30 years ago people generally weren’t really aware of generic testing or any of it’s implications outside of science fiction.
      - weaksauce 5y ago
        I am talking about DNA wrt crimes... it was first proposed as possible in 85 and in the early 90s used for it. I'd say my timeline was fairly ok give or take a few years for an off the cuff recollection of events.
- riedel 5y ago
  Would be rather interesting to create sth like bloom filters from ones DNA to find relatives. In contrast to phone numbers the DNA space here might really be big enough for private "contact" discovery to work ...
  - beaugunderson 5y ago
    23andMe does this already; I've found relatives from some distant parts of the family this way!
- jltsiren 5y ago
  There is plenty of open software and data in genomics. The hard part is knowing what to do, using the software correctly, and interpreting the results. Bioinformatics is still mostly research-level work, so you'll need years of experience and lots of trial and error to get anything done.
  - andai 5y ago
    I'd wager for most people, DNA still isn't a thing they're worried about.
- gremloni 5y ago
  I don’t know if it’s relevant anymore but I ran my SNP data through promethase years ago. It has a ridiculous amount of information.
searine 5y ago
Oxford nanopore isn't that great for resequencing a human genome. Human DNA is too big and the minIon or flongle is too small and error prone. MinIons are best used for long reads for niche experiments like assembly or for field work, in my experience. It is much cheaper, easier, and more accurate to use a service like Nebula Genomics. 300 dollars for an exome is an incredible deal. When looking for deleterious mutations, it is actually really important to have a highly accurate methodology, otherwise you may find errors you think are true deleterious mutations.
- aantix 5y ago
  Nebula offers "Deep Whole Genome Sequencing - We decode 100% of your DNA at 30x" Is the 30x coverage sufficient for finding all deleterious mutations? Or is the 100x option needed?
  - aabaker99 5y ago
    Coverage isn't directly relevant to whether a mutation is deleterious or not. Coverage is about getting accurate reads in the face of short-read sequencing. Modern sequencing will chop up DNA into 200-nucleotide-long fragments and then align those fragments against the reference genome. Because of the variation between individuals, sequencing errors, and the fact that there are only 4 nucleotides, one sequencing read may not be enough to unambiguously determine which DNA is present at what position in the genome. Coverage at a particular genomic coordinate or locus is the number of reads which have been aligned to that position. Depending on the circumstances, clinical use of genomes requires 100x-500x coverage. Depending on your purposes, you may accept less sequencing depth/coverage. If I was just a hobbyist wanting some idea about my genome, 30x would be sufficient for me.
    - aantix 5y ago
      My son has been diagnosed with oppositional defiance disorder. His symptoms greatly subside when he takes Niacin (1000mg/2x/day) along with magnesium l-threonate (2x/day). Was wondering if there was an issue with B vitamin metabolism. Was going to run the data through Promethease, but wasn't sure if the additional fidelity would help my search for a possible diagnosis.
sterlind 5y ago
I might actually try this! I have a disabling genetic disorder (hypermobile Ehlers-Danlos syndrome) for which the genes responsible haven't yet been identified, but there are a few dozen genes of interest. Since the diagnosis is clinical, my geneticist didn't order testing for me, so I've stayed curious. I'd probably approach it by ordering primers for my regions of interest, doing PCR to amplify them, then running it through the flongle in a single shot. Of course anything this DIY would be useless for diagnosis or research - you want Sanger sequencing for accurate transcription of each gene, and whole-genome sequencing for identifying candidate mutations - but it's enough motivation to try such a fun little project. Also I can potentially play along at home with the results of the HEDGE study, which is trying to find the cause of hEDS.
- forgotpwagain 5y ago
  Have you looked into Nebula Genomics? They will do 30X coverage WGS for $299, and will give you the underlying data so you can analyze it on your own (in addition to their analyses). Link: https://nebula.org/whole-genome-sequencing-dna-test/ https://nebula.org/whole-genome-sequencing-dna-test/
  - sterlind 5y ago
    This looks quite amazing. I'd seen services like this, but not at this price point, and not without prescription.
- tito 5y ago
  As a middle ground between DIY and leaving it unknown you could also hire a contract lab to do this with you. As an experiment in this, I found a contract lab, ordered PCR primers, and sent in McDonalds burgers and McFish samples to do species identification. (Result: $300 all in, nothing too exciting, Bovine and iirc Alaskan Cod). The "human sample" bit might be tricky. Doing this today I would check out https://www.scienceexchange.com/ https://www.scienceexchange.com/ Oh and obviously if you're in the Bay Area go to BioCurious (https://biocurious.org/ https://biocurious.org/) or Counter Culture Labs (https://www.counterculturelabs.org/ https://www.counterculturelabs.org/) for all your DIY bio dreams
dcolkitt 5y ago
For anyone wondering if there's any real benefit to having your genome sequence, here's my anecdote. Thanks to Promethease, I found out at a young age that I had hereditary hemochromatosis. This condition basically results in the slow over-accumulation of iron over a period of decades. The symptoms are so non-specific that without genetic testing, it's very rarely diagnosed until major damage has been done. However if detected early, the treatment is dead simple. Regular phlebotomies to keep iron in line. One trip to the blood bank every few months means that the disease has literally zero impact on health or quality of life. Without genenome sequencing, I likely would have lost 10-20 years of life, and even more in terms of quality adjusted years. And this isn't some freak corner case. As many as 1 in 200 Northern Europeans have the genetic condition.
- 1-6 5y ago
  I've been a proponent of regular blood-letting through blood banks. For those who can do it, it's really easy and it also goes to save lives.
- prepend 5y ago
  Sadly promethese sold to MyHeritage in 2019 so I stopped using them due to privacy concerns.
  - deleted 5y ago
    [deleted]
- dekhn 5y ago
  Would a whole genome sequence give you more actionable data than if you just did the normal gene panel test? https://www.labcorp.com/tests/511345/hereditary-hemochromatosis-dna-analysis https://www.labcorp.com/tests/511345/hereditary-hemochromato...
miley_cyrus 5y ago
Sequencing a genome is the easy part -- the difficulty is making sense of all of the data in a clinical/medical sense. I got my DNA sequenced/analyzed by https://www.nagenomics.com https://www.nagenomics.com and found some interesting things that matched personal/family medical history.
- jrhawley 5y ago
  This is definitely true. Even looking at risk SNP databases for a particular disease is fraught with caveats. You really need someone with experience in the field, like a medical geneticist, to interpret the data you get. 23andMe and Ancestry can at least provide that for people, but I don't necessarily like giving up that data to a company to hold for me. But that's cool you were able to find some known markers of your personal medical history
- flemhans 5y ago
  How much did that cost, if you don't mind disclosing?
gravelc 5y ago
0.1X coverage is nowhere near enough to get any useful information. The Nanopore error rate is huge (10-15%), with substitutions, insertions and deletions all common. The required coverage is more like 10X to 30X or more to get some accuracy in base calling and identifying variants. Far far better idea to just pay someone to do short read resequencing. Long read sequencing is great for assembling genomes and finding structural variants. Nanopore looks cheap in the first instance, but it's just not designed for this job. HiFi sequencing gives the best of both worlds - accuracy of short reads and decent length. https://www.pacb.com/smrt-science/smrt-sequencing/hifi-reads-for-highly-accurate-long-read-sequencing/ https://www.pacb.com/smrt-science/smrt-sequencing/hifi-reads... Not accessible to the home user though.
- JackSparrow77 5y ago
  Weird because last time I sequenced with Nanopore, the accuracy was around 95%, and with the new Q20 chemistry it reaches to 98% :) I think you have 5 years outdated information
johntfella 5y ago
I've considered getting my stool tested for microbiome. Another curiosity is Virscan (1) with perhaps the intent on getting the virome tested as well. A lot of my interest comes from the perspective that I have ulcerative colitis. I have read everything about the disease since diagnosis. I don't want to go into everything, but it got to the point where the gastro wanted to prescribe humira and if that failed to move onto pouch surgery. Always being prone to a gamble, I tried drinking raw bovine milk and making enemas from it. To my surprise things began to clear up within a few weeks. This was 6 years ago. I'm symptom free and my most recent colonoscopy was clear. I have attempted to talk to doctors at the local teaching hospital that have a microbiome research initiative but got turned away. The interest was to let them study me, however I get it in that they have other priorities. Either or.. I have the op article printed out as perhaps genome will aide in some home research. No idea. One of the things I suspect is that I've had uc for longer than when it became an issue. Have read it can be present in childhood without much symptoms. So the curiosity is just trying to figure out if it is genetics, environment.. what not. (1) https://science.sciencemag.org/content/348/6239/aaa0698 https://science.sciencemag.org/content/348/6239/aaa0698

184 points by sprague 5y ago

I've been wary about submitting my DNA to a company so this is very intriguing. Is there enough data and/or a community and open software to support things like ancestry and disease profiles locally?

amelius 5y ago
Good question. I'm always afraid most of the useful medical data will be kept secret by these giant corporations, but let's hope this is not already the case.
searine 5y ago
Most of bioinformatics/computational biology is open source and so are most of the data sets. The companies that do this definitely have a 'special sauce' for ancestry, but most all of the disease annotations are public (see dbSNP). As for the paranoia about DNA companies, you are an anonymous drop in the ocean of sequenced DNA. There are laws against using it to inform insurance coverage. Sequencing yourself at one these companies and opting in for use in research is actually really important to collecting the sample sizes necessary to discover new causative variants for disease.
teachingassist 5y ago
It's tricky to organise, but in theory, yes, you can interpret your own results. Ancestry/23andme-type medical results are (in my opinion) almost entirely a nice write-up and display of public databases of research on SNPs, e.g. https://www.ncbi.nlm.nih.gov/snp/docs/entrez_help/ https://www.ncbi.nlm.nih.gov/snp/docs/entrez_help/, https://www.snpedia.com/ https://www.snpedia.com/ You could (for example) submit the data you get to Promethease which will do the processing for you. Promethease is now owned by MyHeritage, so I'm not sure how their terms are looking - I'd be a little cautious about using that.
caymanjim 5y ago
I've been curious about what my DNA says, and went so far as to buy a 23andme kit years ago. I never sent it in, because I don't like the idea of some company retaining that kind of deeply personal data about me. It's useless to resist, though; my sister and some cousins submitted theirs, and that's enough to destroy any real sense of anonymity I might have. I don't have any particular concern; it's just one of the myriad ways that privacy no longer exists.
- weaksauce 5y ago
  > I don't have any particular concern we don't have even the slightest idea of where it could go right now. look 30 years ago and DNA wasn't a thing that people were worried about and now it's catching sloppy criminals. the technology opens up new, unexpected opportunities
  - adenadel 5y ago
    I get your point, but your timeline is pretty far off. The first human gene therapy happened in 1990 so DNA has been a thing for awhile.
    - Retric 5y ago
      The first use of DNA in a criminal case only goes back to 1987. As such 30 years ago people generally weren’t really aware of generic testing or any of it’s implications outside of science fiction.
    - weaksauce 5y ago
      I am talking about DNA wrt crimes... it was first proposed as possible in 85 and in the early 90s used for it. I'd say my timeline was fairly ok give or take a few years for an off the cuff recollection of events.
riedel 5y ago
Would be rather interesting to create sth like bloom filters from ones DNA to find relatives. In contrast to phone numbers the DNA space here might really be big enough for private "contact" discovery to work ...
- beaugunderson 5y ago
  23andMe does this already; I've found relatives from some distant parts of the family this way!
jltsiren 5y ago
There is plenty of open software and data in genomics. The hard part is knowing what to do, using the software correctly, and interpreting the results. Bioinformatics is still mostly research-level work, so you'll need years of experience and lots of trial and error to get anything done.
- andai 5y ago
  I'd wager for most people, DNA still isn't a thing they're worried about.
gremloni 5y ago
I don’t know if it’s relevant anymore but I ran my SNP data through promethase years ago. It has a ridiculous amount of information.

searine 5y ago

Oxford nanopore isn't that great for resequencing a human genome. Human DNA is too big and the minIon or flongle is too small and error prone. MinIons are best used for long reads for niche experiments like assembly or for field work, in my experience. It is much cheaper, easier, and more accurate to use a service like Nebula Genomics. 300 dollars for an exome is an incredible deal. When looking for deleterious mutations, it is actually really important to have a highly accurate methodology, otherwise you may find errors you think are true deleterious mutations.

aantix 5y ago
Nebula offers "Deep Whole Genome Sequencing - We decode 100% of your DNA at 30x" Is the 30x coverage sufficient for finding all deleterious mutations? Or is the 100x option needed?
- aabaker99 5y ago
  Coverage isn't directly relevant to whether a mutation is deleterious or not. Coverage is about getting accurate reads in the face of short-read sequencing. Modern sequencing will chop up DNA into 200-nucleotide-long fragments and then align those fragments against the reference genome. Because of the variation between individuals, sequencing errors, and the fact that there are only 4 nucleotides, one sequencing read may not be enough to unambiguously determine which DNA is present at what position in the genome. Coverage at a particular genomic coordinate or locus is the number of reads which have been aligned to that position. Depending on the circumstances, clinical use of genomes requires 100x-500x coverage. Depending on your purposes, you may accept less sequencing depth/coverage. If I was just a hobbyist wanting some idea about my genome, 30x would be sufficient for me.
  - aantix 5y ago
    My son has been diagnosed with oppositional defiance disorder. His symptoms greatly subside when he takes Niacin (1000mg/2x/day) along with magnesium l-threonate (2x/day). Was wondering if there was an issue with B vitamin metabolism. Was going to run the data through Promethease, but wasn't sure if the additional fidelity would help my search for a possible diagnosis.

sterlind 5y ago

I might actually try this! I have a disabling genetic disorder (hypermobile Ehlers-Danlos syndrome) for which the genes responsible haven't yet been identified, but there are a few dozen genes of interest. Since the diagnosis is clinical, my geneticist didn't order testing for me, so I've stayed curious. I'd probably approach it by ordering primers for my regions of interest, doing PCR to amplify them, then running it through the flongle in a single shot. Of course anything this DIY would be useless for diagnosis or research - you want Sanger sequencing for accurate transcription of each gene, and whole-genome sequencing for identifying candidate mutations - but it's enough motivation to try such a fun little project. Also I can potentially play along at home with the results of the HEDGE study, which is trying to find the cause of hEDS.

forgotpwagain 5y ago
Have you looked into Nebula Genomics? They will do 30X coverage WGS for $299, and will give you the underlying data so you can analyze it on your own (in addition to their analyses). Link: https://nebula.org/whole-genome-sequencing-dna-test/ https://nebula.org/whole-genome-sequencing-dna-test/
- sterlind 5y ago
  This looks quite amazing. I'd seen services like this, but not at this price point, and not without prescription.
tito 5y ago
As a middle ground between DIY and leaving it unknown you could also hire a contract lab to do this with you. As an experiment in this, I found a contract lab, ordered PCR primers, and sent in McDonalds burgers and McFish samples to do species identification. (Result: $300 all in, nothing too exciting, Bovine and iirc Alaskan Cod). The "human sample" bit might be tricky. Doing this today I would check out https://www.scienceexchange.com/ https://www.scienceexchange.com/ Oh and obviously if you're in the Bay Area go to BioCurious (https://biocurious.org/ https://biocurious.org/) or Counter Culture Labs (https://www.counterculturelabs.org/ https://www.counterculturelabs.org/) for all your DIY bio dreams

dcolkitt 5y ago

For anyone wondering if there's any real benefit to having your genome sequence, here's my anecdote. Thanks to Promethease, I found out at a young age that I had hereditary hemochromatosis. This condition basically results in the slow over-accumulation of iron over a period of decades. The symptoms are so non-specific that without genetic testing, it's very rarely diagnosed until major damage has been done. However if detected early, the treatment is dead simple. Regular phlebotomies to keep iron in line. One trip to the blood bank every few months means that the disease has literally zero impact on health or quality of life. Without genenome sequencing, I likely would have lost 10-20 years of life, and even more in terms of quality adjusted years. And this isn't some freak corner case. As many as 1 in 200 Northern Europeans have the genetic condition.

1-6 5y ago
I've been a proponent of regular blood-letting through blood banks. For those who can do it, it's really easy and it also goes to save lives.
prepend 5y ago
Sadly promethese sold to MyHeritage in 2019 so I stopped using them due to privacy concerns.
- deleted 5y ago
  [deleted]
dekhn 5y ago
Would a whole genome sequence give you more actionable data than if you just did the normal gene panel test? https://www.labcorp.com/tests/511345/hereditary-hemochromatosis-dna-analysis https://www.labcorp.com/tests/511345/hereditary-hemochromato...

miley_cyrus 5y ago

Sequencing a genome is the easy part -- the difficulty is making sense of all of the data in a clinical/medical sense. I got my DNA sequenced/analyzed by https://www.nagenomics.com https://www.nagenomics.com and found some interesting things that matched personal/family medical history.

jrhawley 5y ago
This is definitely true. Even looking at risk SNP databases for a particular disease is fraught with caveats. You really need someone with experience in the field, like a medical geneticist, to interpret the data you get. 23andMe and Ancestry can at least provide that for people, but I don't necessarily like giving up that data to a company to hold for me. But that's cool you were able to find some known markers of your personal medical history
flemhans 5y ago
How much did that cost, if you don't mind disclosing?

gravelc 5y ago

0.1X coverage is nowhere near enough to get any useful information. The Nanopore error rate is huge (10-15%), with substitutions, insertions and deletions all common. The required coverage is more like 10X to 30X or more to get some accuracy in base calling and identifying variants. Far far better idea to just pay someone to do short read resequencing. Long read sequencing is great for assembling genomes and finding structural variants. Nanopore looks cheap in the first instance, but it's just not designed for this job. HiFi sequencing gives the best of both worlds - accuracy of short reads and decent length. https://www.pacb.com/smrt-science/smrt-sequencing/hifi-reads-for-highly-accurate-long-read-sequencing/ https://www.pacb.com/smrt-science/smrt-sequencing/hifi-reads... Not accessible to the home user though.

JackSparrow77 5y ago
Weird because last time I sequenced with Nanopore, the accuracy was around 95%, and with the new Q20 chemistry it reaches to 98% :) I think you have 5 years outdated information

johntfella 5y ago

I've considered getting my stool tested for microbiome. Another curiosity is Virscan (1) with perhaps the intent on getting the virome tested as well. A lot of my interest comes from the perspective that I have ulcerative colitis. I have read everything about the disease since diagnosis. I don't want to go into everything, but it got to the point where the gastro wanted to prescribe humira and if that failed to move onto pouch surgery. Always being prone to a gamble, I tried drinking raw bovine milk and making enemas from it. To my surprise things began to clear up within a few weeks. This was 6 years ago. I'm symptom free and my most recent colonoscopy was clear. I have attempted to talk to doctors at the local teaching hospital that have a microbiome research initiative but got turned away. The interest was to let them study me, however I get it in that they have other priorities. Either or.. I have the op article printed out as perhaps genome will aide in some home research. No idea. One of the things I suspect is that I've had uc for longer than when it became an issue. Have read it can be present in childhood without much symptoms. So the curiosity is just trying to figure out if it is genetics, environment.. what not. (1) https://science.sciencemag.org/content/348/6239/aaa0698 https://science.sciencemag.org/content/348/6239/aaa0698