5 ms·

Can this be used with a 23andMe genome to find pathogenic mutations?

sicklyscientist 4d ago
This could be especially useful for people who get a VUS on a genetic test. I’m an ML engineer, not a biologist, and the precomputed Atlas meant I could just look up my own VUS and inspect the outputs directly, without setting up a genomics pipeline myself. I found it really helpful for understanding my variant better. I can also see how easy it would be to over-interpret the output, but I still think there’s a lot of value in lowering the barrier for patients to inspect and understand their own variants.
dekhn 8d ago
Not really, no.
- shevy-java 8d ago
  Why not? There is no logical reason as to why this would not work, IF it works in the first place, which I don't know. In theory the problem space here is finite, so there is of course a way to predict everything. Whether this is the case right now - who knows; I probably don't think it is currently ready. But eventually it will be. And it should not be in the hands of private companies.
  - dekhn 8d ago
    So it sounds like you're coming to this with very little knowledge about biology. I encourage reading up on modern challenges in pathogenic prediction, especially with regards to SNPs: on their own, with the exception of a few diseases, individual SNP predictions are meaningless in terms of actual pathogenicity.
  - chorizo 8d ago
    Because 23andme does not sequence your genome, only substring matches linked to specific gene variants.
MisterMunchkin 8d ago
23andMe and similar companies don't transcribe your entire genome because that would cost way more than they charge you. They just sample a few tiny sections of it.
- willturman 8d ago
  A few as in tens of thousands. 23andMe used a custom Illumina Infinium microarray designed around segments of particular interest. https://www.illumina.com/products/by-brand/infinium.html https://www.illumina.com/products/by-brand/infinium.html
- iooi 8d ago
  fwiw sequencing your entire genome only costs $400 or so from providers like sequencing.com
  - wraptile 8d ago
    Thank you for the recommendation! I've been on a lookout for an affordable full sequence and 400$ is very reasonable. Very excited to just have my DNA on my own computer - this feels like the good kind of sci-fi :)
    - vibrio 7d ago
      What are their data privacy and security policies? That is an important consideration.
      - wraptile 7d ago
        I did fair amount of research, and it seems like they take it seriously with GDPR, HIPAA etc. and all the privacy legalities, but obviously Uncle Sam will have his way with it as it's a US based company (California). They will share your DNA if legally compelled. There is a "permanent delete my data" option, but there's no independent audit that permanent delete actually deletes anything. If you're in EU/California they kinda have to take delete seriously due to GDPR and CCPA, so I think you're safer here. I've been thinking about this a lot, and I'm not sure how "protectable" your DNA actually is because of how easy it is to get if somebody wants to. Obviously having your DNA in US government is bad, but they likely have it already. As I'm an EU citizen I will get the data and use the delete option with fingers crossed that US government doesn't want to destroy me for whatever reason. Seems like they have their hands full with other kinds of destruction anyway lol
MadrasTh0rn 8d ago
23andMe tests SNP's (single nucleotides) that are inferred to be significant in protein function/epigenitics. Those SNP's i believe are testd from primers so what 23andMe does is specifically on the back of previous research and afaik their data isnt technically clinically significant as most findings need confirmation or more tests.
vintermann 8d ago
Probably not any 23andMe haven't already told you about. They test a limited set of SNPs, balancing between ones thought useful for genealogy, ones useful for ethnicity estimates and ones thought useful for health-related things (the latter they would like to make their main selling point, the two former are really all commercial DNA services' bread and butter). It's unlikely that they would luck into testing some unknown SNP which turned out to be relevant for disease.

This could be especially useful for people who get a VUS on a genetic test. I’m an ML engineer, not a biologist, and the precomputed Atlas meant I could just look up my own VUS and inspect the outputs directly, without setting up a genomics pipeline myself. I found it really helpful for understanding my variant better. I can also see how easy it would be to over-interpret the output, but I still think there’s a lot of value in lowering the barrier for patients to inspect and understand their own variants.

dekhn 8d ago

Not really, no.

shevy-java 8d ago
Why not? There is no logical reason as to why this would not work, IF it works in the first place, which I don't know. In theory the problem space here is finite, so there is of course a way to predict everything. Whether this is the case right now - who knows; I probably don't think it is currently ready. But eventually it will be. And it should not be in the hands of private companies.
- dekhn 8d ago
  So it sounds like you're coming to this with very little knowledge about biology. I encourage reading up on modern challenges in pathogenic prediction, especially with regards to SNPs: on their own, with the exception of a few diseases, individual SNP predictions are meaningless in terms of actual pathogenicity.
- chorizo 8d ago
  Because 23andme does not sequence your genome, only substring matches linked to specific gene variants.

MisterMunchkin 8d ago

23andMe and similar companies don't transcribe your entire genome because that would cost way more than they charge you. They just sample a few tiny sections of it.

willturman 8d ago
A few as in tens of thousands. 23andMe used a custom Illumina Infinium microarray designed around segments of particular interest. https://www.illumina.com/products/by-brand/infinium.html https://www.illumina.com/products/by-brand/infinium.html
iooi 8d ago
fwiw sequencing your entire genome only costs $400 or so from providers like sequencing.com
- wraptile 8d ago
  Thank you for the recommendation! I've been on a lookout for an affordable full sequence and 400$ is very reasonable. Very excited to just have my DNA on my own computer - this feels like the good kind of sci-fi :)
  - vibrio 7d ago
    What are their data privacy and security policies? That is an important consideration.
    - wraptile 7d ago
      I did fair amount of research, and it seems like they take it seriously with GDPR, HIPAA etc. and all the privacy legalities, but obviously Uncle Sam will have his way with it as it's a US based company (California). They will share your DNA if legally compelled. There is a "permanent delete my data" option, but there's no independent audit that permanent delete actually deletes anything. If you're in EU/California they kinda have to take delete seriously due to GDPR and CCPA, so I think you're safer here. I've been thinking about this a lot, and I'm not sure how "protectable" your DNA actually is because of how easy it is to get if somebody wants to. Obviously having your DNA in US government is bad, but they likely have it already. As I'm an EU citizen I will get the data and use the delete option with fingers crossed that US government doesn't want to destroy me for whatever reason. Seems like they have their hands full with other kinds of destruction anyway lol

MadrasTh0rn 8d ago

23andMe tests SNP's (single nucleotides) that are inferred to be significant in protein function/epigenitics. Those SNP's i believe are testd from primers so what 23andMe does is specifically on the back of previous research and afaik their data isnt technically clinically significant as most findings need confirmation or more tests.

vintermann 8d ago

Probably not any 23andMe haven't already told you about. They test a limited set of SNPs, balancing between ones thought useful for genealogy, ones useful for ethnicity estimates and ones thought useful for health-related things (the latter they would like to make their main selling point, the two former are really all commercial DNA services' bread and butter). It's unlikely that they would luck into testing some unknown SNP which turned out to be relevant for disease.