First blood test for dozens of hereditary cancers approved by FDA • Hacker News Board

Re: First blood test for dozens of hereditary cancers approved by FDA

#121

Post by yellowcake0 » Wed, Oct 04, 2023, 9:16 AM UTC

renewiltord wrote: post #74

dekhn wrote: post #72

Earlier quoted context omitted.

ClinVar will have many variants associated with disease, but not in a way that a typical layperson would be able to interpret.

Can you give me some keywords to get started with this if you are acquainted with the field? I can try to work my way to something if it's just software that needs to be written and textbooks to read. Would be appreciative. I will try on my own as well.

The variants in ClinVar will have genomic coordinates associated with them, each given with respect to a particular reference genome, e.g.

GRCh38 - chr2:41785474-41785474

or something like that.

You will need to align your FASTQ to one of these reference genomes using a short-read aligner such as BWA-MEM (assuming your genome was sequenced using something like Illumina NGS) to produce a BAM (binary alignment map) file, and then from there use a variant calling tool such as GATK's HaplotypeCaller or Google's DeepVariant to produce a VCF (variant call format) file, which will contain the mutations in your genome. Then you can see if any of the mutations found in your genome match those in ClinVar.

As humans are diploid, you will also need to be cognizant of the zygosity of each mutation, i.e., whether you have a particular mutation on just one of your two chromosomal homologs (heterozygote) or both (homozygous mutant), as this may affect whether or not the mutation is of concern, the variant caller will attempt to determine this for you and report it in the VCF file.

Re: First blood test for dozens of hereditary cancers approved by FDA

#122

Post by dekhn » Wed, Oct 04, 2023, 5:16 PM UTC

yellowcake0 wrote: post #121

renewiltord wrote: post #74

Earlier quoted context omitted.

Can you give me some keywords to get started with this if you are acquainted with the field? I can try to work my way to something if it's just software that needs to be written and textbooks to read. Would be appreciative. I will try on my own as well.

The variants in ClinVar will have genomic coordinates associated with them, each given with respect to a particular reference genome, e.g. GRCh38 - chr2:41785474-41785474 or something like that. You will need to align your FASTQ to one of these reference genomes using a short-read aligner such as BWA-MEM (assuming your genome was sequenced using something like Illumina NGS) to produce a BAM (binary alignment map) fil…

And even if you do all of this, it likely won't give you any actionable information.

Re: First blood test for dozens of hereditary cancers approved by FDA

#123

Post by optymizer » Wed, Oct 04, 2023, 5:35 PM UTC

AmericanChopper wrote: post #102

optymizer wrote: post #101

Earlier quoted context omitted.

We did prenatal tests to ensure that the IVF process we went through actually prevented our CF-genes from combining and causing the fetus to have CF. Also we knew very early there was no Down syndrome. Unlike eugenics, where otherwise perfectly normal humans would have been born, this use case is focused on negative traits that would have resulted in a lifelong tragedy for everyone involved.

> Unlike eugenics, where otherwise perfectly normal humans would have been born, this use case is focused on negative traits that would have resulted in a lifelong tragedy for everyone involved. If the intention was to abort a genetically undesirable pregnancy, then that is literally textbook eugenics.

Sure, if you want to define eugenics strictly in terms of selecting for features, but I think there's a difference between "selecting for A" vs "selecting for !B", with the latter not limiting the existence of A, C, D, etc. On paper these might seem equivalent, but when applied by a society it becomes the difference between "let's breed blond haired blue eyes people" vs "let's not have kids with Down syndrome" and I think "eugenics" has been primarily used to describe the former application.

Re: First blood test for dozens of hereditary cancers approved by FDA

#124

Post by yellowcake0 » Wed, Oct 04, 2023, 6:09 PM UTC

dekhn wrote: post #122

yellowcake0 wrote: post #121

Earlier quoted context omitted.

The variants in ClinVar will have genomic coordinates associated with them, each given with respect to a particular reference genome, e.g. GRCh38 - chr2:41785474-41785474 or something like that. You will need to align your FASTQ to one of these reference genomes using a short-read aligner such as BWA-MEM (assuming your genome was sequenced using something like Illumina NGS) to produce a BAM (binary alignment map) fil…

And even if you do all of this, it likely won't give you any actionable information.

but it will give you some sleepless nights!

Re: First blood test for dozens of hereditary cancers approved by FDA

#125

Post by AmericanChopper » Wed, Oct 04, 2023, 10:01 PM UTC

optymizer wrote: post #123

AmericanChopper wrote: post #102

Earlier quoted context omitted.

> Unlike eugenics, where otherwise perfectly normal humans would have been born, this use case is focused on negative traits that would have resulted in a lifelong tragedy for everyone involved. If the intention was to abort a genetically undesirable pregnancy, then that is literally textbook eugenics.

Sure, if you want to define eugenics strictly in terms of selecting for features, but I think there's a difference between "selecting for A" vs "selecting for !B", with the latter not limiting the existence of A, C, D, etc. On paper these might seem equivalent, but when applied by a society it becomes the difference between "let's breed blond haired blue eyes people" vs "let's not have kids with Down syndrome" and I…

You’re still choosing who gets to live based on their immutable characteristics. Which I would say is still bad, but not for entirely the same reasons as the Nazi program was.

And as I mentioned in another response, if this technology eventually becomes very sophisticated, how do you prevent some sort of gattaca-like situation emerging?

You’re still discriminating upon who gets to live, and “at least it’s not racist” doesn’t seem like a particularly compelling defence of that idea to me. It also doesn’t impact the myriad of other potential downstream issues.

Re: First blood test for dozens of hereditary cancers approved by FDA

#126

Post by rapatel0 » Fri, Oct 06, 2023, 12:08 PM UTC

mschuster91 wrote: post #112

Wohlf wrote: post #96

Earlier quoted context omitted.

You're really out of the loop, Obamacare eliminated excluding due to prior conditions and differing premiums for anything except smoking. In exchange we all got higher premiums, higher deductibles, and worse coverage across the board.

And yet, insurance companies are still making healthy profits [1]. In any case the problem with the US healthcare system is not that now everyone has a sort-of right to insurance, the problem is on the spending side. Y'all spend many thousands of dollars more per capita than the Swiss [2] but have worse metrics across the board. [1] https://www.beckerspayer.com/payer/the-house-always-wins-hea... [2] https://en.wikipe…

There are a confluence of reasons behind this state of affairs.

- A few fundamental flaws of Obamacare that broke the incentive structure of the healthcare and some regulatory capture. (Granted, the incentive structure has always been a little broken even before Obamacare)

- A broken, overly politicized healthcare system in general (something, everyone can agree with)

However, people always seem to gloss over this fact: The United States is responsible for vast majority of R&D and revenue in the healthcare sector. Frankly, the US taxpayer and consumer are subsidizing the rest of the world including the Swiss.

As a US person, I would love to stop this dynamic and stop hearing this tired, patronizing argument.

Re: First blood test for dozens of hereditary cancers approved by FDA

#127

Post by pfisherman » Sun, Oct 08, 2023, 6:06 PM UTC

Gibbon1 wrote: post #108

pfisherman wrote: post #59

Earlier quoted context omitted.

The sci-fi use case is that an prognostic / diagnostic / active learning agent pulling information from EHRs would use this as a prior. More low tech is that you and your physician are more vigilant when it comes to monitoring or testing for certain types of cancer if you have a high impact onco-variant. Keep in mind that prognosis for cancer improves dramatically when you can detect it early.

Even more sci-fi might be drugs that can mitigate the risk. Notable is the recent cocktail of drugs that coax the defective protein in CF to functioning better. There is one cancer gene I know that causes people to develop polyps in their intestines which then go on to become cancerous. Imagine a drug that stops that.

One of the weird things about oncogenes that I have observed is that there is a balance. Perturb them too far one way and you get cancer. Perturb them too far the other and you get a developmental disorder. This is not at all rigorously documented or studied. Just an anecdotal observation.