The Era of Fast, Cheap Genome Sequencing Is Here (wired.com) 32
Emily Mullin writes via Wired: The human genome is made of more than 6 billion letters, and each person has a unique configuration of As, Cs, Gs, and Ts -- the molecular building blocks that make up DNA. Determining the sequence of all those letters used to take vast amounts of money, time, and effort. The Human Genome Project took 13 years and thousands of researchers. The final cost: $2.7 billion. That 1990 project kicked off the age of genomics, helping scientists unravel genetic drivers of cancer and many inherited diseases while spurring the development of at-home DNA tests, among other advances. Next, researchers started sequencing more genomes: from animals, plants, bacteria, and viruses. Ten years ago, it cost about $10,000 for researchers to sequence a human genome. A few years ago, that fell to $1,000. Today, it's about $600.
Now, sequencing is about to get even cheaper. At an industry event in San Diego today, genomics behemoth Illumina unveiled what it calls its fastest, most cost-efficient sequencing machines yet, the NovaSeq X series. The company, which controls around 80 percent of the DNA sequencing market globally, believes its new technology will slash the cost to just $200 per human genome while providing a readout at twice the speed. Francis deSouza, Illumina's CEO, says the more powerful model will be able to sequence 20,000 genomes per year; its current machines can do about 7,500. Illumina will start selling the new machines today and ship them next year.
Illumina's sequencers use a method called "sequencing by synthesis" to decipher DNA. This process first requires that DNA strands, which are usually in double-helix form, be split into single strands. The DNA is then broken into short fragments that are spread onto a flow cell -- a glass surface about the size of a smartphone. When a flow cell is loaded into the sequencer, the machine attaches color-coded fluorescent tags to each base: A, C, G, and T. For instance, blue might correspond to the letter A. Each of the DNA fragments gets copied one base at a time, and a matching strand of DNA is gradually made, or synthesized. A laser scans the bases one by one while a camera records the color coding for each letter. The process is repeated until every fragment is sequenced. For its latest machines, Illumina invented denser flow cells to increase data yield and new chemical reagents, which enable faster reads of bases. "The molecules in that sequencing chemistry are much stronger. They can resist heat, they can resist water, and because they're so much tougher, we can subject them to more laser power and can scan them faster. That's the heart of the engine that allows us to get so much more data faster and at lower costs," says Alex Aravanis, Illumina's chief technology officer. Illumina's new system comes at a steep cost of around $1 million, which makes them more difficult for smaller labs and hospitals to acquire. They also often require experts to run the machines and process the data.
That said, "Illumina's sequencers are completely automated and produce a report comparing each sample against a reference genome," reports Wired. "Aravanis says this automation could democratize sequencing, so that facilities without large teams of scientists and engineers can run the machines with few resources."
Now, sequencing is about to get even cheaper. At an industry event in San Diego today, genomics behemoth Illumina unveiled what it calls its fastest, most cost-efficient sequencing machines yet, the NovaSeq X series. The company, which controls around 80 percent of the DNA sequencing market globally, believes its new technology will slash the cost to just $200 per human genome while providing a readout at twice the speed. Francis deSouza, Illumina's CEO, says the more powerful model will be able to sequence 20,000 genomes per year; its current machines can do about 7,500. Illumina will start selling the new machines today and ship them next year.
Illumina's sequencers use a method called "sequencing by synthesis" to decipher DNA. This process first requires that DNA strands, which are usually in double-helix form, be split into single strands. The DNA is then broken into short fragments that are spread onto a flow cell -- a glass surface about the size of a smartphone. When a flow cell is loaded into the sequencer, the machine attaches color-coded fluorescent tags to each base: A, C, G, and T. For instance, blue might correspond to the letter A. Each of the DNA fragments gets copied one base at a time, and a matching strand of DNA is gradually made, or synthesized. A laser scans the bases one by one while a camera records the color coding for each letter. The process is repeated until every fragment is sequenced. For its latest machines, Illumina invented denser flow cells to increase data yield and new chemical reagents, which enable faster reads of bases. "The molecules in that sequencing chemistry are much stronger. They can resist heat, they can resist water, and because they're so much tougher, we can subject them to more laser power and can scan them faster. That's the heart of the engine that allows us to get so much more data faster and at lower costs," says Alex Aravanis, Illumina's chief technology officer. Illumina's new system comes at a steep cost of around $1 million, which makes them more difficult for smaller labs and hospitals to acquire. They also often require experts to run the machines and process the data.
That said, "Illumina's sequencers are completely automated and produce a report comparing each sample against a reference genome," reports Wired. "Aravanis says this automation could democratize sequencing, so that facilities without large teams of scientists and engineers can run the machines with few resources."
Re: (Score:2)
> Law enforcement is going to love this.
I can't think of any area where they would need full scan. Even facial recognition can be done with only a "few" genes.
Re: "completely automated" (Score:1)
I'll take my chances with the j Edgars!
kind of strange (Score:5, Informative)
Not only was this laborious, but IIRC, the first virus that we had a complete sequence on (V.E.E), took some 3 years worth of work with multiple ppl working on it. I am guessing that back then, we probably spent 1-5 million to do that. And back then, that was a LOT OF $. Some time later, Dengue was done by the lab.
40 years later, it is easy to do this and next to no cost. amazing.
Re: (Score:2)
Some of the new technologies out there blow me away. Like RNAScope. "Hey, want to see EXACTLY what a cell is doing in realtime? Here you go!"
"3D Priting" RNA Viruses (Score:2)
Sequencing is so naughties.
These days for $1000 or less you can mail order your own virus DNA. Just give them a file with a bunch of letters and get back your virus.
When the SARS-2 (Covid) genome was released (a bunch of letters) other researchers did not need a sample, they just printed off the virus and got to work making vaccines.
This means if you want, for example, to see what would happen if you added a Furin Cleavage Site to a bat Coronavirus, that is now relatively easy to do. Just insert the lette
Illumina is almost a monolist (Score:2)
Illumina almost owns the next-generation sequencing market and can basically ask anything for their machines and more importantly the consumables.
I've been working with their machines for almost 15 years and it's always the same story. Yes the newer machines (which come at a pretty hefty price) have lower costs per base, but only when combined with increased throughput. We don't all need 20K genomes per year. We want cheaper sequencing for smaller labs/projects.
Re: (Score:2)
At $200 per genome, you might as well just sequence everyone.
Re: (Score:2)
> At $200 per genome, you might as well just sequence everyone.
So sequencing USA would cost about 3 times the money that was needed for the Apollo project. Or about the same as US highway system or the cost of Vietnam war.
Re: (Score:2)
Show your work.
330 million times $200 is $66 billion in current dollars. The Apollo program cost $257 billion in 2021 dollars. [planetary.org] The U.S. interstate system cost $535 billion. [lauxconstruction.com] The Vietnam War cost almost $1 trillion. [thebalancemoney.com]
So overstating the comparative costs by a factors of four, eight and fifiteen.
I believe did no work at all, just posted those previous projects without checking anything.
Re: (Score:2)
It's also the entirely wrong thing to compare to. The right thing to compare to is the cost of *healthcare*. The US spends on average $12530 *per year* *per person* on healthcare. If a one-time lifetime cost could reduce even a tiny fraction of that risk, it's well worth the cost. We're only going to continue to keep finding more and more genes that link to disease risks.
Re: (Score:3)
At $200 per genome, you might as well just sequence everyone.
A misleading cost. The cost is one million dollars plus $200 per additional genome sequenced.
Re: (Score:2)
At $200 per genome, you might as well just sequence everyone.
A misleading cost. The cost is one million dollars plus $200 per additional genome sequenced.
Rather like saying that the cost of a CPU is $300 is misleading because it is really a 5 billion dollar fab plus the $300.
The sequencer can average up to 64 genomes per day, and if run 6 days a week that is 20,000 a year. If the machine is good for 5 years then that is 100,000 genomes amortizing the total capital cost per genome to an additional $10.
Re: (Score:2)
A misleading cost. The cost is one million dollars plus $200 per additional genome sequenced.
Rather like saying that the cost of a CPU is $300 is misleading because it is really a 5 billion dollar fab plus the $300.
Exactly. Cost depends on how many are sold.
Confusing marginal cost with total cost is a bad economic mistake.
The sequencer can average up to 64 genomes per day, and if run 6 days a week that is 20,000 a year. If the machine is good for 5 years then that is 100,000 genomes amortizing the total capital cost per genome to an additional $10.
Right. So, another way to phrase what I said is that it sequences a genome for $200, but only if you have an application where you need to sequence a hundred thousand genomes.
Re: (Score:1)
At $200 per genome, you might as well just sequence everyone.
I'm not sure if you've seen any info on the BabySeq and BabySeq2 [nih.gov] projects, or the UK government's plans to sequence the genomes of 200k new-borns [newscientist.com] but there are serious ethical considerations in what you suggest.
I do, of course, appreciate that I'm highlighting new-born sequencing, whereas you explicitly mentioned no such thing (albeit 'everyone' does somewhat imply 'children'), and I acknowledge that when it comes to things such as security of data steps can be taken to mitigate the risks, but these are not
Re: (Score:2)
There are alternatives:
https://nanoporetech.com/produ... [nanoporetech.com]
Drive thru genome sequencing (Score:3, Funny)
Now you can get your genome sequenced with fries and a coke. Oh? And did we mention your data is totally secure with us. TOTALLY, except for the major data breach we have every year and a halfâ¦
react (Score:1)
I'm glad of the new tech (Score:3)
This will mean that fully sequencing your genes will be almost as cheap as 23&Me grabbing less than 0.1%, and far cheaper than FamilyTreeDNA's BigY.
This will lead to more discoveries in medicine, yes. But it'll be simultaneous with more discoveries in deep ancestry, as opposed to being either/or.
For me, personally, it won't matter. Already had my full genome sequenced out of curiosity. Nebula was running a sale on their 40x oversequencing, which made it affordable.
Tech support. (Score:2)
Fast, cheap, accurate (Score:2)
Pick 2.
Re: (Score:2)
Fast, cheap accurate, pick 2 refers only to work done by humans, because humans don't scale and humans don't multitask. This is not true for machines. Machines can become faster, cheaper and more accurate at the same time as history has proven e.g. with CPU.or milling machines or car engines or pretty much anything.
not completed until 20 years later (Score:3, Informative)
Left out: "... and despite headline-grabbing press releases, did not completely sequence the human genome."
The Human Genome Project made a decision that it was unnecessary to sequence a lot of the non-coding DNA, known as "junk" DNA, on the assumption it was uninteresting.
This part of the genome was finally sequenced... twenty years after the Human Genome Project declared success. https://www.rockefeller.edu/ne... [rockefeller.edu]
Re:not completed until 20 years later (Score:4, Informative)
Re: not completed until 20 years later (Score:3)
Complete false BS. First off 99% of the DNA sequence IS the so called junk DNA by most definitions. So if scientists did not care about junk DNA they would not have sequenced up to 95 percent of the genome. They could have stopped at 1 percent. The reality is very few scientists in the late 90s, if any, actually thought the so called junk regions were actually junk. Second, it was not even clear if there were some coding regions (aka non-junk) in those parts of the chromosome that couldnâ(TM)t be seque
Re: (Score:2)
Complete false BS.
Sorry, but you are factually incorrect. The announcement that "The human genome has been fully sequenced" occurred when only the coding part of the genome was fully sequenced.
First off 99% of the DNA sequence IS the so called junk DNA by most definitions. So if scientists did not care about junk DNA they would not have sequenced up to 95 percent of the genome. They could have stopped at 1 percent. The reality is very few scientists in the late 90s, if any, actually thought the so called junk regions were actually junk. Second, it was not even clear if there were some coding regions (aka non-junk) in those parts of the chromosome that couldnâ(TM)t be sequenced. In fact most people thought those regions were really important. The reason they didnâ(TM)t sequence it was because highly repeating regions could not be sequenced by the technology of the time. It had to do with repeating code, structural issues, not status of being junk or not.
I'm not sure what your point is here. You seem to be agreeing here that when they announced "the humane genome has been fully sequenced", the human genome was, in fact, not fully sequenced.
Given that you agree with the point I was making, you must be quibbling about the details of wording?
OK, I stand by my wording. You are correct
Re: (Score:2)
You are both correct. When they announced the “essentially complete” human genome, they had sequenced 99% of what they had intended to sequence. It was not the complete genome, but it included what was then known to be the whole exome (all protein coding sequences). The missing heterochromatic regions were initially estimated to be only 5% of the genome, and the technology available at the time couldn’t sequence it. When long read techniques became available and they were able to sequence
Re: (Score:2)
No, ~98% of the genome is non-coding, but not all non-coding DNA is “junk DNA”, which as you note is a highly controversial term. Also, the exome is not concentrated in one spot on one chromosome, so even if they had decided the exome was the only important part to sequence, they couldn’t just sequence the exome. They had to sequence most of each chromosome to get all of the coding sequences on each chromosome.
"You can have it fast, cheap, and good" (Score:2)
Well we see which two they chose.
The DNA is then broken into short fragments (Score:2)
The DNA is then broken into short fragments
But once fragments are sequenced, how do we figure in what order they were in the orignalDNA?
Re: (Score:1)
By reconstructing against reference genomes. One way is Burrows-Wheeler transform as implemented in BWA, a common software used to achieve this. https://bio-bwa.sourceforge.ne... [sourceforge.net]
From this, sequences are aligned and then de-duplicated. https://github.com/molgenis/NG... [github.com]