Talk:Whole genome sequencing

Latest comment: 2 years ago by Darcyisverycute in topic Copied content from Nature paper
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February 28, 2009Featured article candidateNot promoted

This

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This is a rapidly emerging field in biotechnology and medicine. Inclusion of all information pertaining to full genome sequencing technologies as well as the companies involved will be most helpful.--DoctorDNA (talk) 19:59, 22 February 2009 (UTC)Reply

Neanderthal genome

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This article may qualify for inclusion somewhere here. Also the Max Planck Institute for Evolutionary Anthropology. --ROK (talk) 03:46, 23 February 2009 (UTC)Reply

Private firms

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The private firms offering personal genome sequencing should be mentioned (eg 23andme, ...) —Preceding unsigned comment added by 81.246.169.193 (talk) 07:30, 20 April 2009 (UTC) 23andMe is still offering sequencing and ancestry information but not health information. "December 6 2013: Pending an FDA decision, 23andMe no longer offers new customers access to health reports. Customers who received their health information prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will only receive their ancestry information as well as access to their uninterpreted raw data. These new customers may receive health reports in the future dependent on FDA marketing authorization." Source: https://customercare.23andme.com/entries/21252273-What-information-will-I-find-in-the-Health-and-Traits-section-of-my-23andMe-account- — Preceding unsigned comment added by 184.65.53.122 (talk) 23:33, 22 March 2014 (UTC)Reply

Genetic testing in children & adolescents

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There seems to be a lack of consensus about the wording of the section on "Societal Impact". There is a statement by the CEO of a genome sequencing company suggesting that "by 2019 it will have become routine to map infants' genes when they are born". While this passage is merely stating what Jay Flatley thinks might happen, it is far outside the standard of practice and goes against the current guidelines for predictive testing of minors. Whether or not whole-genome sequencing is commercialized is irrelevant. The position about predictive testing of minors (either for prediction of common disease, detection of adult onset disorders for which we have no treatment, or for carrier status of recessive genes) is the same. We assume that the individual (child) would want to retain the autonomy to decide whether or not to undergo such testing as an adult and therefore defer testing until they have the capacity to understand what the implications of that testing might be. The situation is completely different in the case of genetic disorders for which we have effective treatments, but these are better discovered through targeted newborn screening rather than whole-genome sequencing, which reveals other information about which 1) we do not completely understand and 2) the person might rather not know about. Comments? --- Medical geneticist (talk) 21:00, 18 July 2009 (UTC)Reply

Disagree as youre stating a point of view and regardless of whether it is right or wrong it is still a point of view. As reference article pertaining to norms in article describes, norms evolve overtime so all we know is that the norms of yesterday's technology may or may not apply to that which we are capable of today. Therefore it is appropriate to state what norms were and also to state norms may not be applicable because of major technological advancement such as full genome sequencing. --- Atomizer

Thanks for your comment. I want to point out that this issue is not simply "my" point of view, but rather a very well-considered ethical/legal/social issue that has been discussed in great depth by many concerned scientists and physicians. It is in fact the "mainstream" point of view. I have no problem with your point that (some) norms evolve over time. However, I don't understand why you think that norms regarding testing of asymptomatic minors would/should change based on this relatively incremental advancement in technology. See my above point about autonomy. --- Medical geneticist (talk) 12:38, 30 July 2009 (UTC)Reply
By the way, if you have a reference that discusses specifically the issue about the norms of genetic testing changing with the advance in whole-genome sequencing, please provide it. --- Medical geneticist (talk) 12:45, 30 July 2009 (UTC)Reply

Parents have legal right to conduct genetic testing on their children for any phenotype, including screening for diseases or traits. There is no prior determination of need or clinical utility that is required by law or by society. —Preceding unsigned comment added by 69.114.118.190 (talk) 17:15, 14 August 2009 (UTC)Reply

Of course, there is a distinction between what is legal and what is ethical. The guidelines I am referring to are based on ethical principles, not on law. --- Medical geneticist (talk) 18:57, 14 August 2009 (UTC)Reply
I fail to see why whether anyone considers the quote ethical is relevant to whether the quote should be a part of the article. The quoted is the CEO of a company offering the services in question, so it is relevant to the portion of the article about societal impact. I agree that wording shouldn't imply the quoted is correct nor should the placement of the quote sensationalize its content, but neither of these is the case, as there is no opinion in the quote and only the attribution itself implies the view of the quoted. Furthermore, because the quoted was attributed properly, there is no implication that the content of the quote is the "mainstream" opinion of the scientific community. Conversely, "the mainstream opinion of professional medical genetics societies" says just that and not in a quote, but the article itself. This should have the word "mainstream" removed at the very least, though it would be much better to properly attribute the statement per the references that follow. The citations hardly qualify to prove the statement that the simplified representation of what is referenced is the mainstream opinion of all professional medical genetics societies. Lastly, I read both citations and neither state that "presymptomatic testing should be offered to minors only when they are competent to understand the relevancy"; rather, the Borry et al representing the PPPC citation states that minors should be increasingly involved in the process as they are competent to understand the relevancy, not that if they are not competent, the testing should not be offered. It states that all parties making the decision (even if it's only parents) should understand the unique risks associated with the process. Furthermore, the Trott and Matalon, 2009 citation says the exact opposite, arguing that children should be tested and that parents have a right to do the testing. From there, I did find a link to a comment on the article by Jane Karwoski, 2009 stating that most professional organizations discourage testing for adult-onset diseases in asymptomatic children and she further argued that parents should avoid "usurping control over reproductive decisions that, in the future, will rightfully belong to their child". Because of the positioning of the "full text" link for the comment, it could have easily been clicked instead of the "full text" link for the article itself (at least that's what I did the first few times).HarrisonNapper (talk) 05:10, 3 February 2012 (UTC)Reply

Individual (haploid) genome?

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After looking at this article I still can't tell if this is about general genome sequencing (e.g. the public/private effort that "ended" in 2003) or the sequencing of individual organisms' genomes (e.g. sequencing J. Craig Venter's genome in 2007). Could someone inform me as to which it is? And then could I try to make that clear in the intro, even to non-experts?

--Qwerty0 (talk) 02:56, 20 January 2011 (UTC)Reply

You may be a bit confused - in terms of the public/private effort that "ended" in 2003 to which you refer, that is known as the "Human Genome Project" and it already has its own page. The Full Genome Sequencing page covers general genome sequencing, which is also the sequencing of an individual organism's genome (those two terms refer to the same thing). — Preceding unsigned comment added by 76.79.173.105 (talk) 03:43, 25 October 2011 (UTC)Reply
No, I'm referring to the difference between the original human genome and the Venter genome. The 2003 genome was pooled from (both haplotypes of) several individuals. The 2007 Venter genome was of one individual, with the haplotypes resolved.
The point is, there's a difference between discovering the generic sequence of the genome of a whole species and the specific sequence of an individual's genome, including its individual alleles. But after several more looks at this article, it seems that it's not really making that distinction. I suppose it's about both types, really.
--Qwerty0 (talk) 18:45, 11 December 2011 (UTC)Reply

Currency

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There are $ symbols used in this article. What currency is being used here? I've presumed it to be US dollars, and have made the relevant changes. Please correct this if I was mistaken. Nightw 19:37, 27 January 2011 (UTC)Reply

Vague and likely incorrect

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The following comes from the introduction to this article:

Full genome sequencing would have been nearly impossible before the advent of the microprocessor, computers, and the Information Age.

What does that even mean? I'm stumped on what exactly nearly impossible means. Why are microprocessor, computers, and the Information Age grouped together - isn't Information Age OR microprocessors and storage devices sufficient? Finally, I doubt anyone would claim our particular Information Age was necessary before full genome sequencing could occur - hasn't this been happening naturally for as long as this stuff has existed?

Anyway, moving away from criticism and onto suggested fixes: it's certainly true that the technology developed throughout the Information Age has made it easier for us analyse a genome, and much easier for us to record a full genome in such a way that later analysis itself becomes easier. If this is what the original sentence is trying to say, perhaps we can rephrase it along these lines. 137.219.205.222 (talk) 02:49, 28 January 2011 (UTC) Since a full genome is in excess of 3 billion bases for humans, and since sequencing a genome requires (for accuracy) 10 fold coverage, that is 30 billion bases of raw data, do ing full genome sequencing without computers to manage the data would be impossible. Further, reading the raw data off of insturments would be extremely $$,timeconsuming and error prone if humans were doing it; we know this because prior to the introduction of ABI and MegaBace type machines, sequence was read by hand from x ray films, slowly and with errors.Cinnamon colbert (talk) 02:06, 3 February 2011 (UTC)Reply

A genome is actually 6 billion bases, or 3 billion base pairs. And no, full genome sequencing has not been occurring naturally "for as long as this stuff has existed" unless you are referring to DNA replication (which does occur naturally but is very different from genome sequencing). Without computers the Information Age, I do agree Full Genome Sequencing would have been impossible (not nearly impossible but totally impossible). And the Information Age primarily refers to the Internet as opposed to the hardware of microprocessors and computers. — Preceding unsigned comment added by 76.79.173.105 (talk) 03:48, 25 October 2011 (UTC)Reply

problem - no mammalian genomes have been sequenced

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lost in the hype is an inconvienent fact: in the human genome there are large, important areas (centromeres) that have not been sequenced, and probably can't be sequenced with any method currently in or near commercialization. We don't even know how many bases there are in these unsequenced regions Further, I do not believe that current drafts even have the right number of contigs. This is a huge gap bewteen what scientists are telling people and what they actually know - a scandal.Cinnamon colbert (talk) 02:03, 3 February 2011 (UTC)Reply

On the contrary, scientists have been very upfront about the human genome sequence being "unfinished" (http://www.ncbi.nlm.nih.gov/About/Doc/hs_genomeintro.html): "Assembling the sequences is an ongoing process that involves many different steps before the data may be merged into segments of contiguous DNA. NCBI continues to improve the genome assembly by incorporating new data, filling in existing gaps, and increasing overall accuracy." Granted, scientists have been big proponents of this project in order to sustain funding for research, but as usual, it's the media that blows things out of proportion. --- Medical geneticist (talk) 11:11, 5 April 2011 (UTC)Reply

while, you can cite all the obscure scientific referneces you want, but when you see the front page of the new york times, or nature, or science talk about "complete" genomes, the message is clearly not getting thru. IN other words, as peggy noonan put it regarding reagan's bloopers, so what if thousands read the correction in the times the next day; millions heard him say it on tv...Cinnamon colbert (talk) 02:12, 18 April 2011 (UTC)Reply

problem with intro

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this sentance In general, knowing the complete DNA sequence of an individual's genome does not, on its own, provide useful clinical information is, at best, weasely; if you have say cystic fibrosis or sickle cell or tay sachs or any one of many other genetic disorders, sequencing is fully informative, in the sense that it tells if the individual has it, or, in the case of parents, the probability that an offspring will be afflicted (50% for huntington's chorea and other autosomal dominants)Cinnamon colbert (talk) 02:38, 5 April 2011 (UTC)Reply

I think the sentence is perfectly fine. It is true that the complete genome sequence isn't going to tell you any of those things without also knowing the "normal" base at any given position (in order to identify variants or mutations), the annotations of genes and other elements (to know if a given variant is likely to affect a functional element), the genes that are involved in different diseases, the types of changes that cause disease, and ideally the person's medical and family history. That's a whole heap of additional information that is required above and beyond the whole genome sequence, and one of the reasons why this technology has limited clinical usefulness right now. --- Medical geneticist (talk) 11:06, 5 April 2011 (UTC)Reply
I sure hope english isn't your native language...Quote: "doesn't provide useful clinical information"...Do you disagree, as a scientist, that having the sequence of BRCAI or CFTR or DMD does or does not provide useful info ? just answer the question as given; does or does not this provide usful info ? of course it does - infact, if you really are a medical geneticist, then a large part of your job is counseling people who have gotten this sort of news (or maybe, aren't getting this sort of news..)
The sentance is WRONG its not sleeping (monty python parrot)Cinnamon colbert (talk) 02:16, 18 April 2011 (UTC)Reply
There's no need to start your reply with a personal attack about my native language. The point is that the actual raw sequence - the string of letters in the genetic code - is not that useful without a lot of other ancillary information that helps us interpret it in a clinical context. That's a pretty simple concept. --- Medical geneticist (talk) 10:10, 18 April 2011 (UTC)Reply
I fully agree with Medical geneticist's comments. Genome sequencing just provides a lot of letters but unless you know what those letters mean (i.e. unless you are able to analyze and interpret those letters) then a sequenced genome means nothing on a clinical level. For example, even if you can somehow (without any interpretation software) you know that a specific sequence is in the CFTR gene and if compare that sequence to the reference sequence (which again is very difficult to do without analysis), and you found that one of the letters was different, what would that mean? Does it mean the person carries cystic fibrosis? But not all mutations in the CFTR gene cause cystic fibrosis. Does it mean the person carries a cystic fibrosis-like phenotype? But that only applies to specific mutations in the CFTR gene. Just having sequence information provides a person with none of this information - it's only through analysis and interpretation that this is possible. — Preceding unsigned comment added by 76.79.173.105 (talk) 03:57, 25 October 2011 (UTC)Reply

err, not related to the above: but in the intro it talks about various genomes having been sequenced to "...fold" now I've read through the article, and i can't seem to find any reference to what that is actually supposed to mean,( if i've overlooked it ignore this ) i assume it's something to do with aligning chunks. But as a layperson, it's not immediately obvious: might I propose someone with more experience alter/clarify/link?92.28.187.172 (talk) 22:10, 12 December 2013 (UTC)Reply

Citation

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I can't seem to find any references on the following line from the article; "Pacific Biosciences also stated that their second-generation machine, which is scheduled for release in 2015, will be capable of providing a full genome sequence for a person in just 15 minutes for less than US$100". Does anyone know where this comes from? --212.88.77.66 (talk) 08:22, 8 September 2011 (UTC)Reply

Many Problems with Article

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I am a student in molecular biology.

There are many errors and inaccuracies in this article (one example - incorrect reference to Sequenom).

It also badly needs updating.

Unfortunately no time to write more as I am revising for a genetics exam tomorrow.

Marchino61 (talk) 00:50, 23 April 2013 (UTC)Reply

Perhaps you will have time next week, next month, or next year. There will always be more to write about genetics. If you need help getting started then feel free to contact me. Blue Rasberry (talk) 10:33, 23 April 2013 (UTC)Reply

1000 Genome

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Didn't want to edit the main page, but it was announced today that San Diego-based Illumina is going to offer sequencing about $1000 this year with it's new machine, maybe worth adding on the article? News article about it: http://www.bbc.co.uk/news/science-environment-25751958 — Preceding unsigned comment added by 177.3.149.211 (talk) 22:20, 15 January 2014 (UTC)Reply

Commercialisation section

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The comercialisation section of this article is really bloated, two of the main problems seem to be:

  • Firstly, the consecutive addition of information like Complete Genomics sequenced 50 genomes in 2009., which at the time may have been interesting or noteworthy but in the days of the 100K Genome Project isn't worth including. Over time these small additions have built into this huge section that contains very little useful information.
  • Secondly the large number of additions that appear to have been made by, shall we say, interested parties. I've just purged swathes of external links to every sequencing manufacturer you can think of (and then some), as well as at least 5 links to the Illumina article, which was also in the see also section. In the same vein, some of the article seems to be copied straight from press releases, which is obviously a COPYVIO problem and needs to be cut on sight (e.g. this).

My proposed solution is to hack this section to a fraction of its current length and I'm posting here mainly to check for objections or comments but also to note the page state before this large change. (Per BRD I'll probably continue to make these changes but feel free to revert and discuss if you object.) benmoore 22:06, 5 February 2014 (UTC)Reply

Ok I've cut about 7 Kb but plenty more could go. I'm not even sure we need a commercialisation section broken down by year, how about just a couple of paragraphs outlining the main point: that there's some degree of an arms-race between sequencing companies to lower prices, increase accuracy etc. with all working towards the $1000 genome milestone. Paragraphs detailing PacBio's funding rounds in 2009 seem wholly irrelevant to the broad topic of WGS. benmoore 22:51, 5 February 2014 (UTC)Reply
I agree wholeheartedly. I culled even more material (especially project announcements, rather than descriptions of completed projects). The section is in dire need of some good secondary sources to highlight only the most interesting milestones and the overall trends, as you mention. Jmc200 (talk) 17:56, 29 August 2016 (UTC)Reply
Further, the "Disruption to DNA array market" is written a bit like a sales pitch for sequencing technology. I think a comparison to DNA arrays could be interesting, if written in a more balanced way. Jmc200 (talk) 14:38, 30 August 2016 (UTC)Reply

Current techniques extremely biased

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The overall quality of this article is not exactly outstanding, but the Current Techniques section is of particularly poor quality. It does not even mention Illumina/Solexa sequencing though that is the current de facto standard method in the field, but instead starts with Oxford Nanpore sequencing, a technique which certainly has great potential, but is in development since many years and certainly not a current option for any real project. Likewise, SMRT sequencing from PacBiosciences still has a long way to go before becoming truely useful for human whole-genome sequencing projects.

IMO, it would be best to replace the whole rather mediocre section with a link to the much better written sections Next-generation methods and Methods in development from the DNA sequencing article. — Preceding unsigned comment added by Wolma (talkcontribs) 22:24, 23 February 2015 (UTC)Reply

Totally agree. This section is appalling and there is no need to duplicate the history of DNA sequencing. Jmc200 (talk) 13:15, 23 August 2016 (UTC)Reply
OK - I cut this section down. Here is the text that I removed:

Pyrosequencing is a method of DNA sequencing based on the sequencing by synthesis principle.[1] The technique was developed by Pål Nyrén and his student Mostafa Ronaghi at the Royal Institute of Technology in Stockholm in 1996,[2][3][4] and is currently being used by 454 Life Sciences as a basis for a full genome sequencing platform.[5]

Another possible way to accomplish cost-effective high-throughput sequencing is by utilizing fluorophore technology. Pacific Biosciences is currently using this approach in their SMRT (single molecule real time) DNA sequencing technology.[6]

Complete Genomics has developed DNA Nanoball (DNB) technology that arranges DNA on self-assembling arrays.[7]

One possible way to accomplish the cost-effective high-throughput sequencing necessary to accomplish full genome sequencing is by using nanopore technology, which is a patented technology held by Harvard University and Oxford Nanopore Technologies and licensed to biotechnology companies.[8] To facilitate their full genome sequencing initiatives, Illumina licensed nanopore sequencing technology from Oxford Nanopore Technologies and Sequenom licensed the technology from Harvard University.[9][10]

IMO, this section would be better if it were more about specific about the use of these technologies in whole genome sequencing (perhaps their advantages and disadvantages?), rather than just duplicating the DNA sequencing article. Jmc200 (talk) 16:26, 24 August 2016 (UTC)Reply
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Mutation frequencies table

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I think that this is too in-depth for the WGS article: a brief summary of the table's contents would be much better. Jmc200 (talk) 17:04, 23 August 2016 (UTC)Reply

[[User:Kencf0618}}, in this dif you added the following"

You added: Due to the decreasing cost of genetic testing in general one may submit one's genome to crowd sourced scientific endeavours such as DNA.land at the New York Genome Center, an example both of the economies of scale and of citizen science.[11]

References

  1. ^ "Definition of pyrosequencing from the Nature Reviews Genetics Glossary". Retrieved 2008-10-28.
  2. ^ Ronaghi M; Uhlén M; Nyrén P (July 1998). "A sequencing method based on real-time pyrophosphate". Science. 281 (5375): 363, 365. doi:10.1126/science.281.5375.363. PMID 9705713.
  3. ^ Ronaghi M; Karamohamed S; Pettersson B; Uhlén M; Nyrén P (November 1996). "Real-time DNA sequencing using detection of pyrophosphate release". Anal. Biochem. 242 (1): 84–9. doi:10.1006/abio.1996.0432. PMID 8923969.
  4. ^ Nyrén P (2007). "The history of pyrosequencing". Methods Mol. Biol. 373: 1–14. doi:10.1385/1-59745-377-3:1. ISBN 1-59745-377-3. PMID 17185753.
  5. ^ http://files.shareholder.com/downloads/CRGN/0x0x53381/386c4aaa-f36e-4b7a-9ff0-c06e61fad31f/211559.pdf
  6. ^ "Single Molecule Real Time (SMRT) DNA Sequencing". Pacific Biosciences. Archived from the original on February 24, 2009. Retrieved 2009-02-23. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  7. ^ "Complete Human Genome Sequencing Technology Overview" (PDF). Complete Genomics. 2009. Archived from the original (PDF) on March 27, 2009. Retrieved 2009-02-23. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ "Harvard University and Oxford Nanopore Technologies Announce Licence Agreement to Advance Nanopore DNA Sequencing and other Applications". Nanotechwire. August 5, 2008. Retrieved 2009-02-23.
  9. ^ "Illumina and Oxford Nanopore Enter into Broad Commercialization Agreement". Reuters. January 12, 2009. Retrieved 2009-02-23.
  10. ^ [1][dead link]
  11. ^ Zimmer, Carl. "Game of Genomes, Episode 13: Answers and Questions". STAT. Retrieved 2016-08-27.

I moved this here as this just seems confused to me, in a whole bunch of ways.

  • First, what DNA.land wants you to donate is the data from your genome sequencing. They don't sequence you. I am not sure if compacted into what you meant was something like "Due to the decreasing cost of sequencing many people have had their genome sequenced and have the data."
  • I am not sure what you mean by "crowdsourced". With respect to funding and what it works on, New York Genome Center is a very formal entity - it is not but paid for with money from various governments. grants, and $ money donors. Nothing you wrote is relevant to it. Likewise what it works on are formal scientific projects. It isn't "citizen science."
  • With respect to DNA.land... If by "crowdsourced" you mean getting data from people, then it would be an example of that. But the data is worked on by scientists at NY Columbia and NY Genome center, not non-scientists. I guess they are looking to get a big database by getting genomes donated one by one, but that is not exactly an "economy of scale"
  • So neither entity does "citizen science" defined as "scientific research conducted, in whole or in part, by amateur or nonprofessional scientists."

So... Jytdog (talk) 04:03, 28 August 2016 (UTC)Reply

Applications

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Can we add Pharmacogenetics at the applications section in this article ? (this is the use of genetic information to determine which type of drugs will work best for a patient). See also this article on pharmacogenetics KVDP (talk) 17:49, 17 May 2017 (UTC)Reply

Copied content from Nature paper

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This paragraph from the article starting with this text:

In 2018, researchers at Rady Children's Institute for Genomic Medicine in San Diego, CA determined that rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants.

is copied from the abstract of [2] in this edit. Although the licensing permits copying it, I think it could be rewritten and paraphrased better to meet encyclopedic tone and due weight for the article. It's only one study, I put write after it a review of 36 studies which I think holds more due weight in the article. Thanks Darcyisverycute (talk) 06:12, 16 July 2022 (UTC)Reply