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The complete sequence of a human Y chromosome

nature.com

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Re: The complete sequence of a human Y chromosome

#221

Post by freedomben »

jghn wrote: post #57
dekhn wrote: post #30

Earlier quoted context omitted.

Yes, but the HGP didn't make a full sequence either, using their scaffold-based contig assembly. Both groups declared a truce and announced they were "finished with the first draft" 35 years ago: https://www.nytimes.com/1987/12/13/magazine/the-genome-proje... 33 years ago: https://www.nytimes.com/1990/06/05/science/great-15-year-pro... 29 years ago: the competition gets fierce https://www.nytimes.com/1994/02/22/scien…

Lets not forget how Perl Saved The Human Genome Project [1], which I remember seeing in a print magazine at the time. As someone who is in the genomics world now as a software person, I find it amusing that I've gotten more into perl over the last year or so. It has its place, in the way that grep/sed/awk/etc does. [1] https://news.ycombinator.com/item?id=30327812

Re: Perl, I very much agree. I've mostly switched to Ruby and `grep -P` but Perl really does have a place. `perl -pie` is still the most expressive/powerful option in some cases. Even if not directly used much anymore, I think most people vastly underappreciate how much Perl affected it's successors. Even as historical significance it's worthy of admiration.

Re: The complete sequence of a human Y chromosome

#222

Post by mnw21cam »

nullfield wrote: post #215
mnw21cam wrote: post #174

Earlier quoted context omitted.

FWIW, the DNA was 100% sequenced. However, a proportion of that data that came back from the sequencing machine was too similar to each other, so it was impossible to assemble it into a coherent full set of contiguous chromosomes. Imagine it like putting together a jigsaw puzzle, except that the picture on the front of the puzzle has lots of repeating motifs, so you end up with multiple pieces that look identical. Yo…

So if one orders WGS at 30x or 100x from someplace like Nebula, what do you actually get?

Unless they're explicitly saying that you'll be getting long read sequencing, what you'll be getting is a paired-end short read sequencing, likely Illumina (although similar output can be achieved using BGI and Element machines as well). You'll be getting fragments of DNA which have been size-selected to around 400-500bp in length and then sequenced 150bp from both ends, with an unsequenced gap of unknown length in the middle (and possibly an overlap if the fragment is smaller than 300bp), sufficient to cover the mappable parts of the reference genome with around 30 or 100 sequence reads on average. That data can be supplied in a couple of FASTQ files (usually gzipped). They may offer to align that against a reference genome for you, where you'll get a BAM file - make sure you have the same reference genome handy to compare against. They may also offer to detect variants, that is places in the sequenced DNA that are different to the reference, in which case you'll get a VCF file.

Because the sequencing uses short reads, it will not be able to resolve parts of the genome that are repetitive with a repeat unit longer than ~150bp. You'll have all the jigsaw pieces from the puzzle, but you won't be able to reconstruct some parts of the picture. Long read sequencing can help with those, but that's more expensive.

Re: The complete sequence of a human Y chromosome

#223

Post by throwawaymaths »

alexvitkov wrote: post #161
wslh wrote: post #156

Earlier quoted context omitted.

TIL that. I was 100% sure the DNA was completely sequenced. Even have a friend with a sequencing company. It is incredible how ignorant one can be. Thank you 10g1k and HN.

Thought so too, turns out we're right now

I'm not really sure what it even means to be 100% sequenced.

Does that mean that every possible polymorphism is accounted for?

Does that mean that 100% of possible polymorphic sites are known?

What about weird edge cases. You have a tandem repeat that is known, but in some small population of humans, there's two tandem repeats with an island of something else in there.

Re: The complete sequence of a human Y chromosome

#224

Post by throwawaymaths »

10g1k wrote: post #5

For those who don't recall: Back in the Dark Ages, there was a race to decode the human genome. The leading competitiors (wealthiest) were Celera Genomics and the Human Genome Project. After some time, Celera (headed by Craig Venter), announced they had done the deed. However, what Celera had actually done was used what they called a "shotgun method", which meant they took small samples here and there, then built a m…

Pretty sure that the announcement was that the sequence was "essentially complete" (or something like that). Here's a press report from the time that provided the caveat:

http://news.bbc.co.uk/2/hi/science/nature/2940601.stm

> The remaining tiny gaps are considered too costly to fill and those in charge of turning genomic data into medical and scientific progress have plenty to be getting on with.

Re: The complete sequence of a human Y chromosome

#225

Post by throwawaymaths »

delecti wrote: post #180
10g1k wrote: post #5

For those who don't recall: Back in the Dark Ages, there was a race to decode the human genome. The leading competitiors (wealthiest) were Celera Genomics and the Human Genome Project. After some time, Celera (headed by Craig Venter), announced they had done the deed. However, what Celera had actually done was used what they called a "shotgun method", which meant they took small samples here and there, then built a m…

I don't think this was a secret. I remember reading an article (IIRC in Readers Digest) nearly ~20 years ago which specifically referred to it as a "shotgun method". I wasn't (and still am not) enough of an expert to have known that was a less authentic/accurate method, but at least at the time the tone was not that they were doing anything illicit.

if you go over the maths on the shotgun method, not taking into account systematic difficulty in sequencing (like tandem repeats), the likelihood of incomplete coverage vanishes much more rapidly than you'd expect, and after about 5-10x coverage volume, coverage is basically linear in the total amount of sequencing.

Re: The complete sequence of a human Y chromosome

#226

Post by throwawaymaths »

comboy wrote: post #157
10g1k wrote: post #5

For those who don't recall: Back in the Dark Ages, there was a race to decode the human genome. The leading competitiors (wealthiest) were Celera Genomics and the Human Genome Project. After some time, Celera (headed by Craig Venter), announced they had done the deed. However, what Celera had actually done was used what they called a "shotgun method", which meant they took small samples here and there, then built a m…

Anybody familiar with news sources which questioned Celera accomplishment before they admitted how they did it?

http://news.bbc.co.uk/2/hi/science/nature/2940601.stm

> The decoding is now close to 100% complete. The remaining tiny gaps are considered too costly to fill and those in charge of turning genomic data into medical and scientific progress have plenty to be getting on with.

OP is being silly. Nobody was fooling anyone.

Re: The complete sequence of a human Y chromosome

#227

Post by gww »

nzach wrote: post #212
mnw21cam wrote: post #174

Earlier quoted context omitted.

FWIW, the DNA was 100% sequenced. However, a proportion of that data that came back from the sequencing machine was too similar to each other, so it was impossible to assemble it into a coherent full set of contiguous chromosomes. Imagine it like putting together a jigsaw puzzle, except that the picture on the front of the puzzle has lots of repeating motifs, so you end up with multiple pieces that look identical. Yo…

For anyone interested, the problem mostly boils down to the sequence lenght we can read. Modern sequencing techniques allow us o read 200 to 500 bases at a time. So after hat we need do find a way o arrange these short sequences into a single sequence. And this can be prety hard, especially when you are doing 'de novo' assembly[0]. Besides that, there is the fact that some regions of DNA are repeated[1]. [0] - https:…

You are a bit behind on the available read lengths. The Oxford nanopore can produce reads as long as 300kb (k as in kilo) and the PacBio hifi can product 15 to 20kb reads. Finally a now defunct technology by 10x genomics called linked read sequencing also permitted longer regions to be sequences using short reads.

Re: The complete sequence of a human Y chromosome

#228

Post by kelnos »

dekhn wrote: post #219
fao_ wrote: post #217

Earlier quoted context omitted.

It's likely just a typo. LR5 "civilisation"/"civilization" brings up nothing on google. I don't know why you would an LLM to know more. Based on the way the person is using it, it does not seem to equate to the Kardashev scale, as my peer stated

Since the cat is out of the bag, no, it's not a typo. it's related to Kardashev but is oriented around the common path most galactic civilizations follow on the path to either senescence (LR8.0) or singularity (LR8.1-4). Each level in LR is effectively unaware of the levels above it, basically because the level above is an Outside Context Problem. Humans are currently LR2 (food security) and approaching LR3 (artifici…

If we're at LR2, and each level is effectively unaware of the levels above it, how do we know what LR3/4/5/6/7/8/9 are or might be?

Or do you mean that a civilization at a particular level will always be unaware of civilizations above? That doesn't seem to make sense either; I see no reason why a LR4 civ couldn't have knowledge of a LR5 civ, for example.

Re: The complete sequence of a human Y chromosome

#229

Post by SebJansen »

udkl wrote: post #123
kazinator wrote: post #116

Earlier quoted context omitted.

I feel a joke coming on. Mother: "Amy, dear, you hardly touched any of your vegetables. Most of them are still on your plate." Amy: "That's not true, Mom; I completely sequenced them into my tummy using the shotgun method."

Someone submit this to smbc comics !

yes! or XKCD

Re: The complete sequence of a human Y chromosome

#230

Post by nzach »

gww wrote: post #227
nzach wrote: post #212

Earlier quoted context omitted.

For anyone interested, the problem mostly boils down to the sequence lenght we can read. Modern sequencing techniques allow us o read 200 to 500 bases at a time. So after hat we need do find a way o arrange these short sequences into a single sequence. And this can be prety hard, especially when you are doing 'de novo' assembly[0]. Besides that, there is the fact that some regions of DNA are repeated[1]. [0] - https:…

You are a bit behind on the available read lengths. The Oxford nanopore can produce reads as long as 300kb (k as in kilo) and the PacBio hifi can product 15 to 20kb reads. Finally a now defunct technology by 10x genomics called linked read sequencing also permitted longer regions to be sequences using short reads.

Thanks for pointing that out.

My knowledge cut-off period in this domain is around 2018. So it's not suprising that things moved on.

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