Genomics. Personalized medicine. Math.
 

I suddenly regretted that the real life detracted from using an important opportunity.
that is - [B]April 25th was the DNA day[/B]. Here is what NHGRI had to say about that day:
[QUOTE="https://www.genome.gov/dna-day"]National DNA Day is a unique day when students, teachers, and the public can learn more about genetics and genomics. The day commemorates the completion of the Human Genome Project in 2003 and the discovery of DNA's double helix in 1953.[/QUOTE]
...but I missed that day. A workday and so many things to do.

I think better late than never and I will start today. I ran a text search - and we have shockingly nothing about genomics at this forum. I volunteer to answer any questions that might be of interest.

Let's start with the why. Why did I personally find this area of science fascinating?

Well, there are many great reasons. This is a science that in a short decade (or less!) will affect everyone. It is already reaching into lives of a small fraction of the population - the ones who need help (healthy people for now can do quite fine without genomics). This is a science that integrates math (including algorithms, and IT, and data science), physics, biology and medicine - and the most interesting things in the world are integrative. the technology that drives the genomics borrows from other branches as well, - chemistry, engineering, etc. Because of the technological implementation (which involves stochastic processes and sampling) you cannot get away from statistics either (and [I]not [/I]the Mark Twain's kind, "damned lies and statistics" :-)

Let's go on with why you would even listen to me. I think [URL="https://orcid.org/0000-0002-0925-0554"]evidence will show[/URL] that you can trust my experience.

I'll try to link out in this thread to some facts about genomics that are interesting, controversial, shocking even. In some time to come. I cannot promise that they will be well organized, and this will not be a textbook. There will be palatable tidbits. There will be my personal opinions, gathered from science literature and from mass media, too.

Everyone is also invited to contribute, please. News. Questions. Events.

Murder, she wrote
 

There is nothing that grabs people's attention faster then if in the opening shot of the movie, there is murder. Shock and mystery grabs people predictably.

So why don't we start with that. In the last two years there were several cold cases, solved with DNA.
[URL="https://www.nytimes.com/2019/04/01/us/montana-bernhardt-reich-murder.html"]DNA Is Solving Dozens of Cold Cases. Sometimes It’s Too Late for Justice.[/URL]

[URL="https://www.cnn.com/2019/04/24/us/golden-state-killer-one-year-later/index.html"]What we know about the Golden State Killer case, one year after a suspect was arrested[/URL]
Short snippet (emphasis mine):
[QUOTE]Then, in 2018, DNA led to DeAngelo's arrest. [URL="https://www.cnn.com/2018/04/26/us/golden-state-killer-dna-report/index.html"]Authorities used a free genealogy and DNA database[/URL] called GEDMatch to try to track down the killer who had evaded them for decades. [B]They created a profile with crime-scene DNA[/B], and in April 2018, DeAngelo's name emerged in what investigators believed was a pool of possible suspects.[/QUOTE]So, note. FBI did not subpoena the data or force the company otherwise. the exact company here is not to blame - it could have been done with any of them (23andme, ancestry etc). FBI took the evidence DNA and created a social network profile for it. DNA relatives emerged.

The other side of the argument is shocking and in fact is a growing problem for us (hospitals who sequence patients to help them with personalized medical treatment that they need) - people's fraction who don't consent (despite benefit) is growing.
Here is why -
[URL="https://www.nytimes.com/2019/04/25/us/golden-state-killer-dna.html"]Sooner or Later Your Cousin’s DNA Is Going to Solve a Murder[/URL]
[QUOTE]The Golden State Killer case was just the start. Hundreds of cold cases are hot again thanks to a new genealogy technique. The price may be everyone’s genetic privacy.[/QUOTE]Please see the complete articles; I don't quote much from them, they are expected to be read, so this posting should be considered only complete if you visit the links and read some.

[QUOTE=Batalov;514946]Everyone is also invited to contribute, please. News. Questions. Events.[/QUOTE]

My take on this...

Some are really excited to find out who their ancestors are, and willingly submit DNA samples to companies. They might be related to a king or queen from the past. Cool.

On the other hand, they might be related to a serial killer. Or have a predisposition to a preexisting condition which might not be covered by insurance.

Your mileage may vary. FWIW.

The personalized medicine
 

Ok, if it's so bad, why should we do sequence ourselves? (cross-posted, but it's ok)

[B]Let's talk about benefits. [/B]

Without going into details of the DNA, rapid whole-genome sequencing test (rWGS), about 30-45% cases receive molecular diagnosis. Half to 2/3 of these molecular diagnosis do lead to a changed treatment (in some percentage, complete recovery). This is very significant for these patients. For those whose diagnosis cannot be established (the rest, 55-70%), their genome can be stored with their EMR (Electronic medical record) and in short several years may yet get solved. They don't need to take (and the insurer doesn't have to pay for) the test again. This is because the genome will not change (except I am not talking about tumors here - their genome does change; they will need to be re-sequenced) - it is the gene-to-disease association database (ClinVar. HGMD, etc) that are constantly growing. There is a bit of the chicken and egg relationship there, too - more sequenced patients lead to solving more cases already in the queue. (* a short humorous comparison here would be to the SIQS or NFS relationship gathering process; see? if you know factoring, you would see how it works. Side benefit.)

I will let the expert speak - [URL]https://vimeo.com/166830984[/URL]

(We have since improved the turn-around times [URL="https://www.ncbi.nlm.nih.gov/pubmed/31019026"]to under 20 hours[/URL], actually. A doctor who determines - this child is really sick, orders the test - and [B]can get the result[/B] before his/her 24-hour shift is over. This is a bit futuristic.)

For today, I'll just sketch some ideas that I intend to touch upon in time to come.

[B]Math[/B]. Great math trove is in the heart of the DNA sequencing technology. For one, let me compare it to a computational algorithm (cf. Knuth): how does one find a needle in haystack of data. Everyone knows: to find effectively, one needs to index first, and that leads to need to sort. To me, the story how [URL="https://en.wikipedia.org/wiki/Burrows%E2%80%93Wheeler_transform"]B-W algorithm[/URL] was almost never published (because W though that it was a trifle), then how it was not used for decades, how it was dusted off and found better than .gz in .bz2 (in some aspects), and finally how it was found to be astoundingly effective for searching DNA substring in the reference genome - is like a detective page-turner. it is fascinating. Now, every method of DNA alignment is using B-W in its gut. Quite something.

[B]Practical DNA categories.[/B] Many people don't know the differences between DNA and other DNA. I will shed some light. What is in 23andme/ancestry/etc? What is in the medical exome? (What is exome, anyway?) What is the WGS (whole genome sequence)? What is CODIS? What is the cheapest commodity test to say - this = that (and not be wrong with 1/10[SUP]20[/SUP] probabilty)? What is the cheapest commodity test to say - "L..., I am your father"? (you've seen them - in every pharmacy you can get these, but how do they work??)

[QUOTE=Batalov;514954]What is in 23andme/ancestry/etc? What is in the medical exome?[/QUOTE]

Cool. I hope you will drill down on the fact that absolutely no one has any privacy any longer. Particularly since just about every relative is more than happy to share DNA with companies, without notice.

I'm personally OK with this. If my DNA was ever found it would show me and my family was always not involved with any attacks.

Or, at least, that would be the "ground truth".

I share [b]chalsall[/b]'s concerns about insurance companies using DNA data to weasel out of paying claims. I've heard of some of the lame excuses they've used.

In an episode of "Finding Your Roots" (Season 4, episode 8), actress Téa Leoni learned the identity of her maternal grandparents. Her mother had been adopted, and the court records sealed in Texas. They identified her maternal grandparents by using DNA databases. Armed with her name, they applied to have the Texas court records unsealed to get the name of the grandfather. The application was denied because it didn't name [i]both[/i] her mother's parents. So, they went through the DNA data [i]again[/i], and identified her maternal grandfather.

In another episode (Season 5, episode 1), writer George R.R. Martin, author of [u] A Song of Ice and Fire[/u], adapted into [i]Game of Thrones[/i], was a guest. He learned that the man he [i]thought[/i] was his Italian grandfather -- wasn't. They were unable to identify his biological grandfather, but they [i]did[/i] determine that Martin has no Italian ancestry, and is about one-quarter Ashkenazi Jewish.

[QUOTE=Dr Sardonicus;514961]I share [b]chalsall[/b]'s concerns about insurance companies using DNA data to weasel out of paying claims. I've heard of some of the lame excuses they've used.[/QUOTE]

Yeah. It sometimes gets a little ridiculous.

Like, for example, this [URL="https://www.youtube.com/watch?v=9yy0RGTaWYM"]Fluke video[/URL]...

Sorry if you don't think I'm taking you on seriously. I am.

CRISPR-Cas really really really worries me
 

In case you haven't heard about CRISPR-Cas, it is a method that allows the editing of DNA & RNA to be done very much easier. Initial enthusiasm about how this could be used to cure so many diseases has run up against the reality of the complexity of Genomics itself as well as moral & ethical issues.
I am aware of a Chinese scientist who has claimed 2 girls exist whose DNA was edited when they were but an embryo. He tried to make them immune to AIDS, but failed.

Still, the prospect that this could go terribly wrong and produce some run-away virus that causes a pandemic haunts me.

[QUOTE=tServo;514964]In case you haven't heard about CRISPR-Cas, it is a method that allows the editing of DNA & RNA to be done very much easier.[/QUOTE]

Please trust me on this: I know a reasonable amount about this.

Fear is reasonable. Insanity isn't.

What are you going to do about it anyway?

Back in 1987, the BBC Horizon series included a dramatization of the discovery of the double helix in 1953, starring a young Jeff Goldblum as James Watson.
At the time, it was simply called [URL="https://en.wikipedia.org/wiki/Life_Story_(film)"]"Life Story"[/URL], but several TV programs have since had the same name, so it is also known as "The race for the double helix".
If (like me) you know little about DNA, then this is well worth watching - if you can legally access a copy!