Detecting Genetically Engineered Viruses With Metagenomic Sequencing

post by jefftk (jkaufman) · 2024-06-27T14:01:34.868Z · LW · GW · 10 comments

This is a link post for https://naobservatory.org/blog/detecting-genetically-engineered-viruses

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10 comments

10 comments

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comment by harsimony · 2024-06-27T18:37:57.054Z · LW(p) · GW(p)

Exciting to see this up and running!

If I'm understanding correctly, the system looks for modifications to certain viruses. So if someone modified a virus that NAO wasn't explicitly monitoring for modifications, then that would go undetected?

Replies from: jkaufman
comment by jefftk (jkaufman) · 2024-06-28T03:32:00.085Z · LW(p) · GW(p)

if someone modified a virus that NAO wasn't explicitly monitoring for modifications, then that would go undetected?

That's correct. But it's extremely cheap to monitor an additional virus, so there's not much downside to casting a large net.

comment by DirectedEvolution (AllAmericanBreakfast) · 2024-06-27T19:42:31.415Z · LW(p) · GW(p)

Is that 0.2% of people “contributing” to the wastewater? Ie if deployed in an airport, approximately 0.2% of daily airport users being infected might be the threshold for detection? If so, at SeaTac, that would mean around 300 infected users per day would be required to trigger the NAO if I am understanding you correctly.

Replies from: jkaufman
comment by jefftk (jkaufman) · 2024-06-28T03:35:07.866Z · LW(p) · GW(p)

Technically it's 0.2% cumulative incidence not 0.2% prevalence, but depending on the assumptions you make about how long infections last and how quickly they spread they're usually in the same ballpark.

Many SeaTac travelers do not defecate, so your effective sample size is smaller. Possibly too small for this to work well. This modeling is generally assuming larger sewersheds, like municipalities.

Replies from: AllAmericanBreakfast
comment by DirectedEvolution (AllAmericanBreakfast) · 2024-06-28T06:49:13.166Z · LW(p) · GW(p)

Gotcha. Last I emailed Kevin he was suggesting this would be deployed in airports rather than municipalities. So the plan has changed?

It’s true only a fraction of travelers defecate, but it still seems like you’d need an average of about 300 infected travelers/day in an airport setting to get .2% of the wastewater being from them? Or in a city of 1 million people, you’d need something like 2,000 infected?

Replies from: jkaufman
comment by jefftk (jkaufman) · 2024-06-28T10:09:17.839Z · LW(p) · GW(p)

suggesting this would be deployed in airports rather than municipalities. So the plan has changed?

We're also exploring arport monitoring, but airplane blackwater tanks not terminals. Preliminary data from pooled tank samples (you collect between the truck that sucks it out of the planes and the dumping point) looks very good.

infected travelers/day in an airport setting to get .2% of the wastewater being from them

Sorry to keep harping in this, but 0.2% of wastewater from people who've ever been infected (cumulative incidence) not currently infected (prevalence). While shedding is primarily about prevalence (though varying over the course of the infection) for evaluating a system we generally think cumulative incidence is more informative because it tells you much more and how far along the pandemic is.

Replies from: AllAmericanBreakfast
comment by DirectedEvolution (AllAmericanBreakfast) · 2024-06-28T17:39:05.989Z · LW(p) · GW(p)

Preliminary data from pooled tank samples (you collect between the truck that sucks it out of the planes and the dumping point) looks very good.

 

Setting aside economics or technology, would it in principle be possible to detect a variant of concern in flight and quarantine the passengers until further testing could be done?

Sorry to keep harping in this, but 0.2% of wastewater from people who've ever been infected (cumulative incidence) not currently infected (prevalence).

I appreciate the harping! So you're saying that your prelim results show that 0.2% of the sampled population would need to have at some point in the past been infected for the variant of concern to be detectable?

Replies from: jkaufman
comment by jefftk (jkaufman) · 2024-06-29T11:36:15.091Z · LW(p) · GW(p)

Setting aside economics or technology, would it in principle be possible to detect a variant of concern in flight and quarantine the passengers until further testing could be done?

There are two pretty different scenarios:

  1. Initial detection: if you don't already know whether there's something out there, you'll need to do metagenomic sequencing or something similar to identify the pathogen. This is the part of the problem that the NAO is trying to solve. While I haven't looked into the absolute-minimum-sequencing-time portion of the space deeply, my understanding is if you want a reasonable cost-per read you need to use a sequencing method that (counting both the preparation and the sequencing machine running) takes multiple days. So not a good fit for per-flight testing.

  2. Containment: we've learned about a pathogen somehow (ex: someone with unusual symptoms, metagenomic sequencing) and we're trying to keep it from spreading. Now we can use a targeted method, such as qPCR, where there are stand-alone speed-optimized options here that take under an hour (ex: KrakenSense). In this case, the question is, how do you get the samples to test? Ideally you'd get everyone to give a sample before boarding, which you could do a pooled test on while the plane was in flight, but that requires infrastructure and cooperation with the originating country.

you're saying that your prelim results show that 0.2% of the sampled population would need to have at some point in the past been infected for the variant of concern to be detectable?

That's correct. While detection is fundamentally based on the people who are currently shedding copies of the virus, but our modeling counts "time" in terms of the progress of the infection through the population.

comment by Metacelsus · 2024-07-01T13:30:51.257Z · LW(p) · GW(p)

Very cool. I wonder which University of Missouri lab the lentiviral plasmid leaked from...

Replies from: jkaufman
comment by jefftk (jkaufman) · 2024-07-03T11:20:42.300Z · LW(p) · GW(p)

I think it's most likely contamination within the lab doing the nucleic acid extraction, since talking to them they do work with lentiviral vectors.