genomer

The Nanopore Minion is still a thing, but it's sequencing and has higher error rates than competing short-read methods like Illumina's sequence by synthesis.

https://nanoporetech.com/products/sequence/minion

Sequencing DNA with nanopores: Troubles and biases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486125/

Based on what I'm seeing from 23andMe's website they only do genotyping, not sequencing.

https://customercare.23andme.com/hc/en-us/articles/227968028...

"23andMe uses genotyping, not sequencing, to analyze your DNA. Sequencing technology has not yet progressed to the point where it is feasible to sequence an entire person’s genome quickly and cheaply enough to keep costs down for consumers. It took the Human Genome Project, a consortium of multiple research labs, over 10 years to sequence the whole genomes of just a few individuals."

Edit: https://www.23andme.com/total-health

I guess they started providing whole exome sequencing, but I can't find information about what depth they're doing it at.

I wasn't aware of the variability in thymic involution. I guess most studies focus on averages. If you have links to more information about these outliers I'd be very interested in reading up on them.

The most recent literature that I'm seeing is showing the most pronounced time of thymus involution occurring around puberty, suggesting a programmed switch from a growing to reproductive phase of life.

"Regardless of the seemingly crucial role of the thymus in preserving homeostasis, its involution in humans and other mammals begins in childhood and peaks around puberty, resulting in an almost completely non-functional organ in aging." https://www.sciencedirect.com/science/article/pii/S156816372...

In this light the following makes sense (stopping or suppressing the switch to a reproductive life). "Castrating rodents before puberty or reducing the levels of sex hormones [e.g., by using Lupron, which desensitizes the luteinizing hormone-releasing hormone (LHRH) receptors] can attenuate or markedly recover the involution process in aging mice."

Those are interesting cases. A similar but more ubiquitous strangeness is somatic mosaicism, specifically in the brain where it seems that "no two neurons are genetically alike."

I was in line for the Terminator ride at Universal Studios when I stumbled onto this article a few years back. Couldn't stop thinking about it the rest of the trip.

https://www.scientificamerican.com/article/scientists-surpri... “The idea is something that 10 years ago would have been science fiction,” says biochemist James Eberwine of the University of Pennsylvania. “We were taught that every cell has the same DNA, but that’s not true.”

Edit:

Reading into this more again for the first time in a while. I'm amazed at how large some of these differences are. Many having 1 million base pair copy number variants.

"Single cell sequencing of endogenous human frontal cortex neurons revealed that 13%-41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975283/

Couple this with...

"Megabase-scale copy number variants (CNVs) can have profound phenotypic consequences. Germline CNVs of this magnitude are associated with disease and experience negative selection. However, it is unknown whether organismal function requires that every cell maintain a balanced genome. It is possible that large somatic CNVs are tolerated or even positively selected." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772019/

I can't imagine our brains are just accumulating mutations of this size for no reason.

My favorite theory so far is that it has to do with memory indexing. https://www.frontiersin.org/articles/10.3389/fgene.2020.0037...

Age is probably the biggest influence on a "healthy" immune system. I haven't kept up with recent research, but if memory serves the immune repertoire (diversity of T and B cell receptors) decreases essentially linearly with age.

Here's some supporting research from a quick search. https://journals.aai.org/jimmunol/article/192/6/2689/1552

Edit: some fun but possibly pontificating tangents

This seems to be part of the reason why vaccines have had relatively poorer efficacy in elderly populations. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901832/ https://www.nature.com/articles/s41586-021-03739-1

I'm hopeful that cancer and immune profiling will be able to be used in tandem to (1) identify cancer early and (2) identify gaps in the immune repertoire to facilitate (3) design of antibodies that specifically target the cancer.

I'm surprised as well. I thought the problem with cancer is that the immune system doesn't react/detect it and therefore might not provide a discernible signal.

Microsoft Research was a partner in the joint collaboration. Pretty sure this was the research that culminated in the T-Detect Lyme product that Adaptive Biotech launched last year (definitely some Adaptive representation in the publication).

https://investors.adaptivebiotech.com/news-releases/news-rel...

It’s what you think it is, and it happens to more than just mice. I toured a bioengineering lab where they were actively severing the spines of chimpanzees to perform fiber rerouting experiments. I think the normal citizen never thinks much if at all about this kind of thing because they’re never exposed to it. A few researchers have opened up to me personally about their personal psychological trauma caused by involvement with animal experimentation. A couple PhD candidates I know changed fields entirely. One to ecology and another to environmental engineering. I personally moved forward with bioinformatics.

Edit: that isn’t to say that this result isn’t exciting for human welfare. We’ll see if it translates…

That's an interesting point and I completely agree, but wouldn't America's already real lack of "supply" buffer this a bit? I have to wait several weeks to get into my personal family doctor, and it took over 4 hours to be admitted during our last visit to the ER (we went in because of a suspected ectopic pregnancy, which it turned out to be).

It seems like the physician shortage will only continue to worsen. https://www.aamc.org/news-insights/press-releases/new-findin...

Edit: Basically, I think a lot of people will still be left without adequate health care in minor cases, but at least the most urgent cases will be taken care of without leaving people bankrupt.

I was surprised by a probiotic addition the other day as well. It was added to a vegan protein powder I bought off the shelf.

Are you insinuating that I didn't read the comment? I take such offense to this.

How else do we dissuade people who don't read an article from jumping to ignorant conclusions and filling the message board with tripe?

The article didn't focus solely on quins.

An example of a different class: "Researchers have shown, for example, that aminoglycoside antibiotics can cause deafness by damaging mitochondria in the hair cells of the ear."

More general statement: "They reported that antibiotics in several classes triggered oxidative stress — a build-up of reactive, oxygen-containing molecules — in mitochondria, inhibiting their function across a range of mammalian cells, as well as in mice."

I interpreted the article as saying that quins are the most obvious example of antibiotics causing harm, but one example for where they cause harm (mitochondria) is a problem shared by other antibiotics. Unfortunately there isn't a test for evaluating mitochondrial damage in the body. Since we can't test, we don't know the real extent of damage done by any antibiotic to human cells. More research is needed.

Directly from the article.

"Until recently, investigations into the side effects of antibiotics have focused on how the drugs disrupt the human microbiome, says James Collins, a medical engineer at the Massachusetts Institute of Technology in Cambridge."