aroch

> However–and here’s the rub–some 25 years after the human genome was sequenced, and despite huge efforts to link genes and disease, there are almost no SNPs that tell you anything consequential about your health. If you have a genetic disease, you almost certainly already know about it, and if you don’t know, then the 23andMe data just isn’t going to reveal anything.

For someone who “knows genomes”, this is a brain dead take on microarrays. Lots of the content on arrays _is_ directly tied to a phenotype because there’s limited space so we directly test variants that are known to cause problems!

Is he really claiming that BRCA1/2 variants don’t increase risk of breast cancer in a meaningful way? Or that there aren’t tons of people who are XXY who don’t know even though it’s the hidden cause of many infertility problems?

This is just such a bad take it is hard to take anything said here seriously

I’m a fan of Saramonic’s MV2000 (https://saramonicusa.com/sr-mv2000-large-diaphragm-usb-studi...) is an affordable, good quality cardiod mic.

Frequently available for $50 and supports live headphone pass through if that’s your jam.

I have ‘ccat’ aliases to the original cat binary

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.

Eh, your results look perfectly fine, especially for a budget sequencing run. Keep in mind there are a lot of repetitive DNA sequences that don't map well (search "mappability track" for more info). Depending on the reference they used, these may even be masked out and thus no alignment can even be attempted.

No one should be BLASTing individual reads... And pretty much no one is going to be assembling with OLC, even for ONT data.

On the products page it says they provide FASTQs, aligned BAM and VCF. Which is exactly what one would expect. They're almost certainly just running the DRAGEN pipeline (or something similar) and giving you the output it creates.

Not for home gamers, no. ONT is fairly low throughput and the prep is surprisingly difficult to do well without experience. You would need to run tens of flow cells to get enough sequencing data.

I have no skin in this particular game (Though I work in the sequencing industry), but... I don't think anyone is fooled/trying to trick anyone when they say "whole genome sequencing" or that they sequence 100% of the genome. That is the term of art for non-targeted/unenriched sequencing of DNA (nb: it may be RNA/ribosome depleted, so fine it's technically enriched but not in a meaningful way). Also exons are genic region, are you thinking introns (arguably genic or at least adjacent), or promoters/enhancers and chromatin state?

Lifetime license does not mean lifetime support. I get that that might be annoying, but why or how could they warranty third party software, that they don't control or version themselves, indefinitely?

Yes, but if your child is school age -- schools which are now increasingly going to in person instruction -- and you are immunocompromised, what are you going to do? Same question if you live in a multi-generational household, but now there are grandkids going to school and kids going to work.

I see elsewhere you're claiming that long Covid isn't a thing. It is, full stop. Unless you're suggesting that living with lung and heart damage caused by Covid isn't a complication of Covid?

Not necessarily, you could have an immuno-compromised parent/grandparent

The point of vaccinating kids is:

1. They still get sick, even if asymptomatic, and can bring it home to the house where older people live 2. I don't know if there are published case report / data yet, but anecdotally the new strains are much more likely to cause complications and require hospitalizations for younger children. 3. Even asymptomatic infectious seem to cause "long covid" (Something like a third of long covid cases were asymptomatic). Potentially life-long alterations to lung or heart function doesn't sound like fun

The answer to "Why are they investigating?" is simple and, in fact, driven in part by the pharmaceutical industry itself.

First: The rate of thrombosis in AZ recipients is the less than it is in the general population -- Gen pop, ~.1% [1], AZ ~ 0.001% [2]. There is no evidence that the vaccine causes substantially higher risk. Also, the populations being prioritized for vaccination are a higher risk population for DVT to begin with.[1]

AZ, along with effectively every pharma company out there of note, takes the reporting of adverse drug responses (ADRs) very, very seriously. Both FDA and EMA require ALL companies that produce a labeled product (aka a drug you can "buy" and isn't only available in a trial setting) to investigate and report on every instance of a reported potential ADR. Companies want to investigate because they want to be able to keep selling their drugs. Regulators want to investigate because they want to limit ADRs as much as possible.

From the therapeutic point of view, it is bad if the treatment causes ADRs but also some may be unavoidable because of how the treatment works -- think chemo and cancer. The safety window for a drug is determined by balancing the therapeutic gain of treatment (usually, shorter time to recovery, increased QOL, or, in the case of cancers, increased life span/PFS) with the number and severity of known adverse effects. You might hear about cancer patients "cycling" their treatments, this is to allow time for the body to recover from known/expected ADRs.

Any way, this was a long winded way of saying every entity involved -- drug manufacturer, regulators, doctors, patients -- wants reports of ADRs investigated.

[1] https://www.ajmc.com/view/overview-of-venous-thromboembolism "The overall incidence of VTE is 1 to 2 per 1000 person-years in the general population, which rises to 8 per 1000 person-years in people older than 85 years"

[2] https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazene... 30/5,000,000

If you have a new model, hold the ionizer button for 5 seconds and the indicator light will turn off.

Strongly suggest using Let's Plot from JetBrains instead. It's much closer to ggplot2 in api and results.

https://github.com/JetBrains/lets-plot

The Telomere-to-Telomere consortium has made fantastic progress on this in the last year or two: https://genomeinformatics.github.io/CHM13v1/

Thanks to them we now have a nearly completed genome, only missing the deconvoluted rDNA array segments (~12mb or so, we know the sequences since they’re basically identical but no one has accurately placed the individual array variants yet).

Sample prep, particularly if you want truly long reads, is 100% the hardest part.

Funnily, there are people out there who want to teach army/marine grunts on the front line to run minIONs. Most of the work is on making the sample prep automated and idiot proof.

This isn’t the case anymore. Pathogen surveillance labs use Nanopore for single-base resolution variant calls to determine antibiotic susceptibility and to “fingerprint” against known and previously sequences isolates.

I think you're stuck in the biotech == people mindset.

On the bacterial side, it is fantastic for quickly sequcinging and closing genomes. Personally, I think the killer use case is field portable and real time sequencing of pathogens. I've worked with groups (.gov and private, defense and health related) that want to put minION + flongles to use in applications like early detection for bio terrorism and pathogen surveillance.

Over the last few years there have been several (4-5) instances of British subs nearly striking surface ships in their home waters. Also running aground right outside their home port in 2010. Not exactly reassuring.

The US Navy is much bigger and has global operations. They're just as guilty of being careless but they also have proven war fighting capabilities. No one is asking the British to sail by as a show of power and solidarity.

Calling the British navy a battle ready fleet would be rather a positive attitude. Their submarine and surface ship captains don't know how to navigate, running aground and into other boats. And their aircraft carriers don't even have enough crew/planes and will deploy US Marine Corp units to meet their full complement. It will likely take the UK 15-20 years for the two new Carriers to be at full operating capability (2009-TBD, probably 2024 at the earliest).

That being said, the US could stand to spend less on military funding.

Ah, I think so!

Oh Haxies, I remember writing run-time patches (aka, cracks) to bypass licensing/registration for several pieces of software. There was a common framework, whose name no eludes me, that could be almost universally patched giving access to tens (100s?) of software.

Lead dev here.

While you're not wrong that we might be under-estimating risk, I'll note that we do take into consideration seroprevalence in our calculations (so called, ascertainment bias). We provide estimates for two cases; 5x and 10x under-counting bias.

And you are right, that risk is additive (to a degree) if you go do multiple parties. And people are terrible at doing this sort of calculation. Our messaging, in our manuscript/press/social media has always been to limit gatherings of any size, and mask and gather outside as much as possible

Lead dev here... Huh, didn't think I'd ever see my work show up on HN. Sadly getting an .edu institution to fork over the money for better scaling is hard... Even when it gets them unlimited free press.

The easiest is to send e-coupons to frequent shoppers?

You see them a lot in biological network / pathway / association studies. I personally hate them, because they're hard to read and comprehend. Many times a heatmap conveys the exact same data in a more digestible way. Alas, chord diagrams can be pretty and make it seems like the analysis is much fancier than it really is.

Oh, hmm, that's very interesting and not something I would have thought about! :)

That was our feeling about the two products as well, the limitations w/ TileDB-vcf though sort of forced our hands. I was (and still am) of the opinion TileDB would be a good variant store since it does do so many of the things we want and does them well

Hail.is is what we landed on. There are some things we don't like with it too but weren't deal breakers