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I know that there are some efforts from scientists working with bladder cancer to perform liquid biopsy from urine for detection and monitoring of the cancer such as this one.

I've been searching online - but the "wastewater" search term gives me tons of hits about "microbiome" and several types of pathogens.

But I'm really interested in sequencing the sewage to find and analyze human DNA. I have been wondering about liquid biopsies to get an estimate of the cancer status of a population.

I immediately think of several problems:

1. Technical Feasibility

  • Would we expect to find enough human nuclear DNA within the samples (taken across several days)?

2. Law and Bioethics

  • Is it legal in the US or European Union?
  • It could be difficult to get informed consent of all people who are connected to a certain sewage system. You may get informed consent from all residents but what about visitors?
  • It could be difficult to opt out of such study the wastewater without a) moving to a different place b) using a septic tank.
  • I only found this elaborating other privacy issues: its just about Cov-19 and drug testing; both of which are not able to identify individuals at a genomic level.

I'd appreciate your experience and thoughts and references!

[Edit] as suggested in the comments: I have posted part 2 of the question to the law stack exchange here

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    $\begingroup$ Given the availability of sets of human reference-haplotypes I think it should theoretically be possible to gather some additional information to common mutations like SNPs even from sub-optimal waste-water. Just you have to be aware how incredibly polluted human DNA would be by incomparably higher DNA-concentrations from other species like microorganisms. Still, as it is possible to identify the whole range of micro-organisms from soil-samples using NGS, one can easily evaluate whether sequenced stretches are uniquely human. Anyways, why not directly get high-quality human DNA samples? $\endgroup$
    – KaPy3141
    Jun 30 at 10:45
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    $\begingroup$ The U.K. tests wastewater for COVID currently post.parliament.uk/monitoring-wastewater-for-covid-19 $\endgroup$
    – Tim
    Jun 30 at 23:38
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    $\begingroup$ @ilamengl Either way, questions about the law and ethics are off-topic, and so is having multiple questions. Stick with the original bit about the scientific aspect of sequencing from waste-water and if you are interested in the legal aspect, maybe ask a question in law.stackexchange.com $\endgroup$
    – user438383
    Jul 1 at 11:48
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    $\begingroup$ @user438383 given that people who have written proposals for scientific project had to think about those things and ask their local bioethics commission I feel like I got more chances here than in law... $\endgroup$
    – ilam engl
    Jul 1 at 11:52
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    $\begingroup$ @ilamengl Any "philosophical or ethical questions related to biology" are explicitly off-topic here, per the site help page. $\endgroup$
    – jakebeal
    Jul 1 at 13:09
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As it turns out, you are not the first to have this idea. Prior research claims that it is, at least in principle, possible to conduct epidemiology of cancer by sequencing on wastewater DNA for biomarkers.

The ethics of this approach also need not be problematic because narrowly targeted sequence amplification focused on biomarkers like SNPs will not typically produce enough information to identify an individual.

The practicality of this approach is a major open question, however, given the small and variable nature of the signal.

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    $\begingroup$ If you can get mtDNA, then in principle you can get other DNA as well. The key issue remains signal levels. $\endgroup$
    – jakebeal
    Jun 30 at 17:40
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    $\begingroup$ @ilamengl a sewer grate? Sorry, couldn't resist. $\endgroup$ Jun 30 at 23:59
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    $\begingroup$ @BolucPapuccuoglu LOL a Freudian slip. $\endgroup$
    – ilam engl
    Jul 1 at 10:38
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    $\begingroup$ @jakebeal thanks for answering the technical part. About the other part of the question: are you aware of any US or European laws that would prevent scientists from sequencing human DNA from the sewer without consent given it would be hard to get consent? $\endgroup$
    – ilam engl
    Jul 1 at 10:39
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    $\begingroup$ @ilamengl that might be a better questions for Law $\endgroup$
    – Pureferret
    Jul 1 at 10:44
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As already hinted in the answer by @jakebeal, the low concentration (high dilution) of human DNA in waste water would mean that we need huge sequencing depth in order to detect something. This is not the case when dealing with urine or feces. This is also not the case when sequencing bacteria in waste water, since we are dealing then with the strains that can live and multiply in water, i.e., they are present in important quantities. Moreover, we are interested in them only when they are present in high quantities, when they are potentially harmful.

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    $\begingroup$ The research group of the paper jakebeal linked used filters -> less water more cells... $\endgroup$
    – ilam engl
    Jul 1 at 12:48
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    $\begingroup$ @ilamengl it seems that their main achievement is precisely overcoming the problem that I described in my answer. It is a strong claim - if this is really the case, we might expect this done commercially in a few years. Note that they didn't do sequencing, and that they look only at mitochontdrial DNA (a small part of the DNA contained in a human cell). $\endgroup$ Jul 1 at 12:55
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    $\begingroup$ @ilamengl it is human mtDNA. I think the catch is that they have a library allowing to amplify mtDNA. I am not sure, whether the same can be done for all of the nuclear DNA. If not, you have to shotgun sequence everything that is found in the water, which is the premise of my answer. $\endgroup$ Jul 1 at 13:13
  • $\begingroup$ Again, I am aware that it is human mtDNA because I've actually read the article ;p but we both know that we cant find the same kind of info as within the nuclear portion of human DNA $\endgroup$
    – ilam engl
    Jul 1 at 14:56
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    $\begingroup$ @ilamengl in most cases one can sample such data in less complicated ways. $\endgroup$ Jul 1 at 15:54
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Reputedly Osama bin Laden was tracked this way

... according to Water and Wastes Digest citing Time Magazine, but few of the details are known. Given that 10 milligrams of feces is sufficient to amplify desired markers from DNA, you would need only consider the number of people living "upstream" to determine how much material you should need to collect overall, and how many sequences you would need to run to find the right one. Maybe with some clever efforts to separate material into microwells you might be able to isolate one or more cells from the target of the search away from all others.

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