[dekhn]

What you're describing is a very reasonable research topic with some supporting evidence.

What I'm saying is that nobody has delivered on any of the huge claims about the genome which genomicists made for the last 20 years, specifically in terms of actionable human health.

it's time to start calling the bluff.

[samchorlton]

I'm not exactly sure how you can say that.

The following have been revolutionized by the human genome project and subsequent technological innovation in sequencing:

-Non-invasive prenatal diagnostics

-Screening for cancer with cell-free DNA

-Rapid and accurate diagnostics for children with suspected genetic disorders

-Targeted cancer therapeutics

Many of these are already in routine clinical use in high income countries and result in significant improvement in human health.

[dekhn]

The impact is minor and most of the progress did NOT come from HGP data.

I worked in genomics for 20 years. I have deep knowledge of biology and medicine. And the reality is, for the amount of money invested, the actionable medical returns have been relatively tiny and industry continues to not invest in sequencers for a good reason.

[acmj]

> the actionable medical returns have been relatively tiny and industry continues to not invest in sequencers for a good reason

I agree with this, but I disagree with the following:

> most of the progress did NOT come from HGP data.

Without HGP (Human Genome Project), many biological discoveries in the past two decades would have become much more difficult.

> it's a huge waste of investment until we understand the multigenicity of diseases better

If you don't invest, you will never approach a solution. Applied science goes nowhere without a solid foundation in basic science.

[abcc8]

None of the techniques you describe are reliant on WGS. I wholeheartedly agree that sequcning has revolutionized medicine, but WGS isn't there yet.

NIPT uses low-coverage sequencing to identify aneuploidies for chromosomes 13,18,21 and some larger microdeletion syndromes - this is not WGS.

Cell free cancer screening is panel based and assays specific, known driver mutations.

Rare disease diagnostics can be WGS based (and some of the rapid 48h WGS studies of NICU babies are compelling from a technical standpoint) but most diagnoses identified via WGS can also be found via WES + chromosomal microarray.

Targeted cancer therapeutic target identification is panel based for most patients, as WGS doesn't identify too many targets for FDA-approved therapies that a panel + IHC + FISH + fusion testing won't.

[searine]

>What I'm saying is that nobody has delivered on any of the huge claims about the genome which genomicists made for the last 20 years, specifically in terms of actionable human health.

I mean. Sure, sequencing the human genome didn't solve our problem overnight, and you can't sequence a genome at a vending machine for a nickel to tell your future, but I think there has been an avalanche of medical data derived from the genome and that is only continue to get bigger.

Now that we are really starting to figure out the polygenic risks and the single deleterious variants and their links with phenotype, people will have a much better picture of what their future might hold (and how to prevent it).

I don't think it was ever a bluff. The problem just turned out harder than we thought it was going to be.

[dekhn]

it didn't turn out to be harder than I thought it was going to be. I came into this in the 90s fully prepared for the idea of polygenic risk. In my opinion, most people who did molecular biology first think that way, while most people who learned mendelian genetics don't.

I had my genome sequenced a few years ago by Illumina. They had a big slick presentation, blah blah blah, ApoE1, etc. When the genetic counsellors came to my genome they said "huh. you don't have any risk factors". I checked and each of their risks was from an existing gene panel, so the WGS wasn't valuable (it's on PGP, if you want to work with it https://my.pgp-hms.org/profile/hu80855C).

I talked in more detail with the counsellors. Turns out, whenever they saw a novel variant that wasn't covered by a gene panel they were googling the variant and skimming the abstracts of papers.

It was at that point I realized the difference between research, PR, and actionable medical data.

[searine]

>it didn't turn out to be harder than I thought it was going to be.

Fair.

I've done my as well. Most of the "company" sites don't tell you much, which I think is a legal thing. They aren't cleared to release clinical predictions from genotypes, so they just... don't. I ended up running my through promethease (which mines SNPepedia) and found quite a bit more than what was reported.

I work with some certified clinical geneticists and yeah they do take a much closer look, but at the end of the day its all just sequencing and interpretation. I think its mostly just safeguards to keep bad actors at bay.

PGP looks interesting. I see that you submitted phenotype data. I didn't know they had a questionnaire with that. That's actually really interesting. I need to see what kind of questions they ask.

[et2o]

This was a talking point like 10 years ago which isn’t remotely true today