[HN Gopher] The era of fast, cheap genome sequencing is here
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       The era of fast, cheap genome sequencing is here
        
       Author : ColinWright
       Score  : 75 points
       Date   : 2022-10-01 12:24 UTC (10 hours ago)
        
 (HTM) web link (www.wired.com)
 (TXT) w3m dump (www.wired.com)
        
       | mattnewport wrote:
       | And yet the era of being able to do anything really useful with
       | the information has yet to arrive.
        
         | Der_Einzige wrote:
         | Clustering, dimensionality reduction, frequent pattern matching
         | can get you a lot of the way there.
        
         | FollowingTheDao wrote:
         | This is the biggest misconception. I have literally reverse my
         | hyperlipidemia, hypertension, and been able to get off all of
         | my meds for my schizoaffective Bipolar Disorder because of what
         | I have learned from my genetics and changing my diet/lifestyle
         | to suit what my body needs.
         | 
         | Just because doctors do not know what to do with it (they are
         | decades behind most research) it does not mean you cannot learn
         | about this and take action on your own.
         | 
         | Just knowing my FADS1, FADS2 genetics was enough to change my
         | diet to seafood only and raise my HDL from a consistent 35 to
         | over 55 in three weeks. Doctors put me on a statin which
         | lowered my HDL to 25.
        
           | dominotw wrote:
           | > seafood only and raise my HDL
           | 
           | Seafood helps everyone with HDL. Is 35 -> 55 not possible
           | with those genes that you mentioned ?
        
         | mbreese wrote:
         | Rare disease diagnosis, newborn screening, molecularly targeted
         | cancer therapies...
         | 
         | We're starting to get some good utility from sequencing.
         | Currently whole exome is more informative than whole genome.
         | But, there are definitely some good clinical uses!
        
           | sacul wrote:
           | My daughter has a rare genetic disorder, cardiofaciocutaneous
           | syndrome (CFC), and it was not until 2 years in that we were
           | able to get a diagnosis after a whole gene sequence. It was
           | game-changing to get the diagnosis, because it connected a to
           | a community and to doctors who could help.
           | 
           | https://rarediseases.info.nih.gov/diseases/9146/cardiofacioc.
           | ..
        
         | cjbgkagh wrote:
         | That future is just not evenly distributed yet.
        
         | pfdietz wrote:
         | Sequencing cancer cell genes is quite common now, to determine
         | just what kind of cancer is there and which treatments are
         | appropriate.
        
           | dominotw wrote:
           | GP probably meant for completely healthy people who are the
           | target audience for doing these .
           | 
           | Also the cancer drugs like PARP inhibitors seem to be helping
           | everyone regardless of mutation status in clinical trials. So
           | the connection is much less clear.
        
             | pfdietz wrote:
             | There are many cancer drugs that target mutations in
             | specific proteins. Just what treatment will be given for a
             | cancer often depends on what's been mutated.
        
       | derekja wrote:
       | sequencing continue to drop in price far faster than moore's law.
       | https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequen...
       | 
       | Here is the archive of the wired article, btw:
       | https://web.archive.org/web/20221001173347/https://www.wired...
        
       | giuliomagnifico wrote:
       | This should be a good news, because with DNA test you can find
       | some hereditary diseases, but I'm a bit skeptical about the
       | privacy, in particular when I read things like this: "Mass DNA
       | Collection in the Tibet Autonomous Region from 2016-2022"
       | https://citizenlab.ca/2022/09/mass-dna-collection-in-the-tib...
       | 
       | The law will absolutely have to adapt to these changes.
        
         | bpodgursky wrote:
         | I have an honest question: what are the specific negative
         | consequences you, personally, are worried about if your genome,
         | today, was made completely public?
        
           | colinsane wrote:
           | during extreme wartime or societal setback, we often see
           | society look for scapegoats. the outgroups created in living
           | memory have been based on social standing but also ancestry
           | and things tightly related to the genome.
           | 
           | if/when the time comes of a meaningful societal regression
           | like this, i want it to not be so easy to drag me into it.
           | it's precautionary.
        
           | giuliomagnifico wrote:
           | For example an insurance company can rise the price of your
           | contract if they know that you are genetically predisposed
           | for some diseases.
        
             | lotsofpulp wrote:
             | In the US, a health insurance company cannot price premiums
             | based on health or any pre existing conditions.
             | 
             | https://www.healthcare.gov/how-plans-set-your-premiums
             | 
             | > FYI Your health, medical history, or gender can't affect
             | your premium.
             | 
             | However, life insurance, long term disability insurance,
             | and I presume other types of insurance are free to use
             | health data for pricing. Of course, if genetic data was
             | known to be worth it for predicting probability of death or
             | disability by a certain age, those insurance companies
             | would already be requiring applicants to provide genetic
             | data.
        
             | bpodgursky wrote:
             | I'm asking at a personal level, because in the US this
             | genetic discrimination is against federal law, and I
             | (personally) have 0 fear that an insurance company will
             | seek out and use this information to illegally discriminate
             | against me.
             | 
             | Are you worried that companies will not respect this law?
             | Or are you not US based.
        
               | rnk wrote:
               | It's illegal but companies will figure out a way to work
               | around it. Why can't they just require your authorization
               | as part of getting insurance? You might notice lots of
               | services require you to give up certain privacy rights. I
               | don't want the phone company to sell my location data, I
               | don't want apps on my phone to sell my location data.
               | There are all these tenuous yet successful ways where
               | your right to opt out is overcome. I'm happy to click in
               | boxes in apps, I've done it lots of times, I turn off
               | location history when possible. But because I carry a
               | phone I believe it's certain that some apps somewhere are
               | storing my location. Same for having a recent car with a
               | data modem in it. And then there are license plate
               | readers. I want to disallow all of these things, but the
               | battle is basically lots as far as I can tell.
        
               | novok wrote:
               | That just means the laws don't have teeth. Often if they
               | do, they straight out say it's illegal to even get
               | 'authorization' or anything approaching it. It would be a
               | straight out ban vs. an "ok with consent" which is what
               | authorization is about.
               | 
               | You can't sign a contract to sign yourself into slavery,
               | it's just straight out illegal. And thus you don't see
               | anybody being signed into slavery via contract in the
               | USA, and there many other things that act this way in
               | law.
        
               | lotsofpulp wrote:
               | > It's illegal but companies will figure out a way to
               | work around it. Why can't they just require your
               | authorization as part of getting insurance?
               | 
               | Because it is highly regulated, with no known examples of
               | insurance companies and regulators colluding to
               | incorporate health data for pricing purposes.
               | 
               | https://www.healthcare.gov/how-plans-set-your-premiums
               | 
               | For example, you can even figure out your health
               | insurance premium in the state of NJ just based on this
               | pdf:
               | 
               | https://www.state.nj.us/dobi/division_insurance/ihcseh/ih
               | cra...
        
           | JZL003 wrote:
           | The thing is it's not much data in absolute terms, but it's
           | not going to change for over human timescales and tells you
           | something about your entire family, going back generations in
           | the past and many in the future. On the other hand, look at
           | GWAS studies, if you have many people and know if they get a
           | disease or not, you can narrow down exactly what parts of the
           | genome are implicated in the disease, and start designing
           | drugs for it. It's hard work and doesn't always work, but it
           | allows us to go from high level disease phenotype -> exact
           | mechanistic problems
        
             | bpodgursky wrote:
             | Yeah and I'm digging into this because I personally would
             | _much_ prefer that these GWAS studies have access to my
             | genome and medical data, so they can design drugs for
             | whatever my specific genotype is. I think it 's far more
             | likely that this will benefit me and my children, than hurt
             | me.
             | 
             | I'm not telling other people they are wrong to be afraid,
             | but I want to understand the exact mechanism of those
             | fears.
        
               | JZL003 wrote:
               | If you're interested and a US citizen, look into the All
               | of Us program by NIH. They're going to sequence a million
               | people's genome (!!) and allow researchers to use it. And
               | they're doing it in a very careful safe way. It will mean
               | many researchers will have your deanonymized genome (and
               | it's up for debate if it's possible to truly future-proof
               | deanonymize a genome) but it's not sketchy at all and
               | will be a huge help for future generations IMO.
               | 
               | And if you're in another country, especially european
               | ones, look into other research programs, there are lots
               | round
        
               | FollowingTheDao wrote:
               | Why drugs? These GWAS studies should be looking at
               | nutrition.
        
               | JZL003 wrote:
               | I guess I agree on principle and diet is understated. But
               | let's say, as has happened recently, you're looking at
               | Alzheimer's or lewey body syndrome and you find the gwas
               | returns a lot of results for a certain cellular pathway
               | (like a stress response or where a cell breaks down
               | misfolded proteins, leading to plaques). You can look for
               | small molecule drug which targets that, or try a fancier
               | treatment to target that exact protein. But how would
               | that insight extend to diet?
               | 
               | Beyond just eating more health (in whatever way) and
               | exercising more, which does go a long way. Thse drugs are
               | trying to be extremely targeted and intricate in now they
               | work
        
           | sometimeshuman wrote:
           | Would you want a dating App telling your potential match all
           | of your negative genetic predispositions ? How about your
           | employer ? Or your parents, would they have raised you
           | differently if they had unnecessary paranoia about a
           | predisposition that you would never manifest.
           | 
           | Human nature values first impressions and you can expose your
           | flaws after you have established your reputation a bit. This
           | data has the potential to short-circuit that and could lead
           | to yet another technology that is maladapted to human nature.
        
             | [deleted]
        
         | Dracophoenix wrote:
         | This will certainly put a damper on the sperm donation market.
        
           | quesera wrote:
           | An individual sperm cell does not contain a full genome.
           | 
           | You cannot even reliably determine a donor's hair color, from
           | a single sperm cell.
           | 
           | I imagine it's much more difficult to reconstruct a full
           | genome from a sperm donation than from, say, saliva on a
           | discarded cup.
        
             | chromatin wrote:
             | This comment is misleading, and possibly wrong depending on
             | what you mean by "full genome" (not an accepted technical
             | term).
             | 
             | A sperm cell contains one complete haploid genome.
        
               | quesera wrote:
               | You're right, it's not as simple as I described.
               | 
               | But (my bio is rusty) a haploid genome (gamete) cannot
               | fully represent the genome of a diploid human.
               | 
               | If you're looking for genetic disorders, these will often
               | be the result of recessive traits, right? So having only
               | half of the chromosome sets is not indicative.
               | 
               | That's my example of hair color. With a full genome
               | sequence, you could determine the person's hair color,
               | but with a haploid genome, you could not.
               | 
               | If OP's joke is about the privacy implications of sperm
               | donation, then saliva seems more risky.
        
               | omgwtfbyobbq wrote:
               | From what I've read, recessive genetic disorders tend to
               | be worse, but there are plenty of dominant and polygenic
               | disorders with _varying degrees of penetrance.
               | 
               | _ This I think indicates some other genetic and/or
               | environmental factors we don't have a good grasp of.
        
               | d110af5ccf wrote:
               | A _single_ sperm cell can 't. But you presumably have an
               | awful lot of them in a single sample. So this seems
               | irrelevant to the privacy concerns being discussed here.
        
               | quesera wrote:
               | ...and that's what I said. It would be _more difficult_
               | than from saliva.
        
             | etiam wrote:
             | As you're probably aware, most people who donate sperm opt
             | for more than a single cell...
        
               | quesera wrote:
               | Right. Hence "more difficult" than from saliva.
               | 
               | Think about it. Each sperm cell gets a random mix of your
               | chromosome sets. There are 2^23 possibilities.
               | 
               | But of course you only need to find the matched pair for
               | each chromosome. So you'd only need a few hundred cells.
               | 
               | I'm not a geneticist, but that sounds like a much harder
               | genome sequencing/assembly problem than the fully matched
               | set you'd get from saliva etc.
        
       | nanomonkey wrote:
       | My father died of pancreatic cancer this week after getting a
       | diagnosis 36 days prior. Since then I've been on a minor crusade
       | to find methods of making sure I have a better diagnosis of
       | anything similar.
       | 
       | Full body MRI can be had for ~$2k. I can imagine going in and
       | getting a genome sequencing and an MRI scan done, and then over
       | the years having a much better idea of the changes going on in
       | your body as you age, along with an evolving map of what to look
       | out for.
       | 
       | It's exiting, and yet I'm worried about handing over information
       | that could be used against me by corporations, the government or
       | insurance companies.
        
         | FollowingTheDao wrote:
         | Sorry man, my father died of pancreatic cancer as well. I have
         | found two homozygous SNPs in my ABO gene (rs505922, rs657152)
         | that are linked to Pancreatic Cancer. ABO needs manganese as a
         | cofactor so I eat a lot of mussels.
         | 
         | They gave my father one year if he went on Chemo and the chemo
         | killed him in there weeks.
         | 
         | Check out these links about the ABO gene and Manganese in
         | pancreatic cancer.
         | 
         | https://pubmed.ncbi.nlm.nih.gov/12649190/
         | 
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657095/
         | 
         | https://pubmed.ncbi.nlm.nih.gov/12700280/
         | 
         | I suffer from a lot of genetic stuff that I have fixed
         | understanding my genetics. That is more valuable than any harm
         | that could be done with my genetics.
        
         | walnutclosefarm wrote:
         | My condolences. My wife has lost both her mother and brother in
         | similar "bolt from the blue" fashion. It's hard.
         | 
         | But, before you conclude that you want to try whole body MRI as
         | your response, I recommend you read this: https://cancerimaging
         | journal.biomedcentral.com/articles/10.1.... It's heavy going if
         | your're not au fait with statistics, but important. The
         | potential for more harm than good is quite real.
        
         | dominotw wrote:
         | i am sorry for your loss. That must be such a shock to everyone
         | in your family.
         | 
         | We are getting HRR genome testing done for my father this week
         | for his prostate cancer. Some of the PARP inhibitors seem to
         | have decent success in prostate cancer.
        
         | divbzero wrote:
         | I am very sorry for your loss.
         | 
         | I know there are efforts like Galleri [1] to detect cancer
         | early using liquid biopsy [2] but I don't know how effective
         | they are at the moment.
         | 
         | [1]: https://www.galleri.com/
         | 
         | [2]: https://en.wikipedia.org/wiki/Liquid_biopsy
        
         | pavlov wrote:
         | Maybe get your MRI and genome done in Europe which has very
         | strong protections for this kind of data?
        
         | etrautmann wrote:
         | My wife is a physician and this is a contentious issue.
         | Virtually any full scan will turn up things that seem like a
         | cause for concern when you're fine. The risk of false positives
         | is fairly high when testing is nonspecific/un-targeted. This
         | results in real stress, difficult decisions, and often times
         | worse care.
        
           | m463 wrote:
           | I was wondering when I would see this answer, since that's
           | what they would always say on House.
           | 
           | I still think there are probably big obvious things that need
           | to be caught early.
        
             | jghn wrote:
             | It's tricky. At a population scale it looks more and more
             | like early detection for many things causes more harm than
             | good. On the other hand, if you're the person who could
             | have had a better outcome with early detection it's hard to
             | argue that point.
        
           | [deleted]
        
         | zemvpferreira wrote:
         | My condolences for your loss.
         | 
         | My own father is a physican and very against any elective exams
         | himself. His reasoning is that his colleagues are excessively
         | interventive so the less medicine, the better. I wish your own
         | father had been diagnosed in time but I can see the downside in
         | doing too many exams as well. Doctors won't be able to keep
         | their hands off treating any little lump they find, even if
         | it's to your detriment.
         | 
         | Case in point, surgery for back pain causes said pains to
         | worsen at about the same rate as it improves them.
        
           | hawk_ wrote:
           | What you do when you find something out is still a choice. If
           | that backpain isn't getting in the way of most of your
           | lifestyle then the risks of a surgery aren't justified. A
           | lump in the pancreas well I think most of us would be better
           | served by finding that out earlier than later.
        
           | novok wrote:
           | That partly comes from the liability / malpractice system of
           | the USA. They are induced to jump on everything so they don't
           | get sued by malpractice lawsuits. The amount of detrimental
           | behavior in medical system driven by this stuff is extremely
           | saddening and if you know doctors, how much they think /
           | worry about this stuff is so fucking annoying and sad.
        
           | _tom_ wrote:
           | While I totally understand his point about excessive
           | intervention, ignorance is not the answer. You absolutely can
           | say "no" to doctors.
           | 
           | Of course, with tests that are of themselves dangerous,
           | that's another issue. Skip those if the risk/reward is too
           | high.
           | 
           | Getting diagnosed too late is much worse than having to say
           | no.
        
           | godmode2019 wrote:
           | I agree, often having more information is worse because you
           | notice things and over react to things that would otherwise
           | go unnoticed and fix them self.
           | 
           | I noticed this first when tracking sleep data, but it can
           | also be applied to many other areas were humans try fix small
           | problems but tend to make things worse.
        
       | gavinray wrote:
       | It's not common knowledge, but there's an algorithm called
       | "genomic imputation"
       | 
       | It can take incomplete data, like the kind you get from 23andMe,
       | etc, and magically "fill in the gaps" to compute the majority of
       | the rest of your genome
       | 
       | There used to be a free service https://impute.me that would do
       | this for you
       | 
       | https://twitter.com/lassefolkersen/status/154763708634953728...
       | 
       | Search Google Scholar for "Lasse Folkersen", he is active in the
       | field and has a lot of great papers about this
        
       | bilsbie wrote:
       | I recall this being predicted something like 10 years ago. I
       | wonder why a slowdown happened.
        
       | peter303 wrote:
       | The second identifiable person to have his genome sequenced-
       | James Watson- had around 30 known genome defects at the time.
       | However most of them did not manifest as disease. That is a
       | mystery.
        
         | FollowingTheDao wrote:
         | SNP changes in genes are not usually mutations that cause
         | "defects". Most usually they increase or decrease risk for a
         | disorder based on more of a polygenic profile.
        
         | tejtm wrote:
         | For small enough values of defect, it is par for the course.
        
       | sometimeshuman wrote:
       | Can someone recommend where one can order a full genetic sequence
       | currently in the US and get the raw data ? It seemed highly-
       | regulated when I last checked and required it be order through
       | your doctor. The article touches on this a bit how the price gets
       | into the thousands due to markups and counseling.
       | 
       | Also how many full sequences would I have to get before the data
       | is statistically sound. Since there is likely a base pair or two
       | that will be different between the cells (maybe) and the
       | sequencer hardware and process will likely have errors too. My
       | gut tells me 10 to 20 but perhaps that seems like overkill since
       | many base-pairs might be junk/repeats/irrelevant anyway and the
       | raw data will have some confidence indication as well IIRC.
        
         | jghn wrote:
         | You should be looking for 30x coverage.
         | 
         | There are a number of companies that will do 30x WGS and give
         | you the BAM file. I believe Nebula is one of them, but know
         | there are other names out there.
        
           | aroch wrote:
           | Nebula most likely ship your samples to China for processing
           | and sequencing because it's so much cheaper. While that might
           | not be a deal breaker for some, I would personally prefer my
           | sample not be shipped elsewhere.
        
           | FollowingTheDao wrote:
           | Stay away from Nebula. I had such a hassle with them and
           | after six months of complaining with mostly no response I had
           | to threaten then with a civil suit and they finally replied
           | "your sample was no good, here is your money back."
        
         | chrisrohlf wrote:
         | I asked this same question not long ago and the CEO of a well
         | known company in this same research area reached out and
         | recommended Veritas Genomics
         | https://veritasgenetics.com/mygenome/
         | 
         | I've yet to finish the order process but I share this here
         | because in my research of companies providing full sequencing
         | services I never came across them and yet they seem far more
         | reputable than others. Current SEO for these services turns up
         | a lot of sketchy companies.
        
           | theNJR wrote:
           | Any idea how much this costs? The order buttons on their
           | website are greyed out for some reason
        
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