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Medicine Science

The New Technique That Finds All Known Human Viruses In Your Blood 111

schwit1 writes with this story at the Atlantic that profiles Ian Lipkin and his new method for quickly detecting all known human viruses in a sample: Ian Lipkin, a virus hunter from Columbia University, recently received a blood sample from colleagues at the National Institutes of Health. They came from a man who had received a bone-marrow transplant and had fallen mysteriously ill, with evidence of severely inflamed blood vessels. In analyzing a similar case a few years back, Lipkin had discovered a new polyomavirus, part of a family that can cause disease in people with compromised immune systems. Perhaps this new case would yield another new virus. It didn't. Instead, when Lipkin's team ran the sample through a system that they had devised to detect human viruses, they found that the man was infected with dengue virus. In hindsight, that made sense-he had recently returned from Vietnam, where dengue is prevalent. But the thing is: The team wasn't looking for dengue virus.

"It wasn't what we anticipated, but we didn't have to make a priori decisions about what we planned to find," Lipkin says. "When people analyze samples from people who are ill, they have some idea in mind. This is probably an enterovirus, or maybe it's a herpesvirues. They then do a specific assay for that particular agent. They don't usually have the capacity to look broadly." The new system, known as VirCapSeq-VERT, barrels past this limitation. Lipkin, together with fellow Columbia professors Thomas Briese and Amit Kapoor, designed it to detect all known human viruses, quickly, efficiently, and sensitively. By searching for thousands, perhaps millions, of viruses at once, it should take a lot of the (educated) guesswork out of viral diagnosis.
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The New Technique That Finds All Known Human Viruses In Your Blood

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  • Unfortunately ... (Score:1, Insightful)

    by Anonymous Coward

    ... the technique also shares all your personal biological data with third parties with implied consent upon usage.

  • by Anonymous Coward

    Let's figure out what's wrong with him and get him a cure, STAT.

  • by ColdWetDog ( 752185 ) on Wednesday September 23, 2015 @08:38PM (#50586677) Homepage

    "You have a virus, specifically a bargoburomyopolyfluenza 2 virus."

    "That's great doc, what do we do to treat it?"

    "Take two aspirin, call me in the morning."

    • by Anonymous Coward

      "Take two aspirin, call me in the morning."

      Of course, this is important for individual diagnosis. But it's the longer term implications on the epidemiology side that are absolutely huge.

      In another decade or two it will be possible to check everyone for contagious illness in all public spaces (in developed countries, at least) and to then quarantine anyone who is infected. Basically, infectious disease will become a distant ugly memory. And, of course, vaccines will be obsolete (again, for everyone in developed countries).

      Back in the late '80s and ea

      • Except the people that refuse to be checked, because with the vaccines gone, it will be these scans that cause autism

        Then there will be people who have never been exposed to a vast array of illnesses and because of that have underdeveloped immune systems. They'll take a trip someone (an undeveloped country) and die a few hours after getting off the plane.

      • by Bruce Perens ( 3872 ) <bruce@perens.com> on Wednesday September 23, 2015 @09:47PM (#50586901) Homepage Journal
        What about the human beings who have virus DNA incorporated into their genome? That's pretty much all of us.
        • by ColdWetDog ( 752185 ) on Wednesday September 23, 2015 @11:08PM (#50587191) Homepage

          In intact blood (well treated, processed correctly) the genomic DNA will be in cells which can be spun out quickly to create plasma. In fact, most lab tests are done on cell free fractions because the proteins and assorted other molecules bugger up the process.

          You should also be able to determine in flanking sequences (if any). If you have a lot of extraneous DNA, it probably doesn't come from a free floating viral particle.

          And finally, since the vast majority of viruses have some sort of protein capsid and are of a fairly constrained size, you can always fractionate the blood to include only those sized structures.

          So, it is a potential issue but one that can be overcome in a fairly straightforward fashion.

          • by AmiMoJo ( 196126 )

            molecules bugger up the process.

            The jargon in these medical articles always goes way over my head.

            • by dcw3 ( 649211 )

              molecules bugger up the process.

              The jargon in these medical articles always goes way over my head.

              Pull the foreskin back next time.

            • const int one = 65536;

              As an aside (that means off-topic, guys) this looks like part of a fixed-point arithmetic implementation. It may not be as silly as you think.

              • by AmiMoJo ( 196126 )

                Sure, that's exactly what it is. I can't remember why it was needed as the .NET stuff it exists in handles floats just fine, and performance wouldn't be an issue... Anyway, I just thought it was indicative of the general quality of the code. Slightly nonsensical, but you can see what they were trying to do and of course they picked a really terrible variable name.

                I wasted many hours of my life fixing bugs in that thing, including a tricky memory leak. I remind myself of it to make sure I'm never tempted to

        • Those genes are not expressed, and we don't have copies of those viruses floating around our bloodstream.
          • Those genes are not expressed, and we don't have copies of those viruses floating around our bloodstream.

            Probably, and for the most part. But we used to think the genome was mostly "junk DNA" before we understood that much of it was homeotic in function. It seems to me that virus copies would not be conserved over time unless they were serving some function.

            • Well, the only function they would need is the ability to get themselves replicated. There isn't a need for them to have any function in the larger picture of the body. But I read the same thing, many of the genes are turning out to be not as quiet as we thought.
      • Re: (Score:2, Insightful)

        by Anonymous Coward

        So GATACA but without the benefits of improved DNA, Got a virus? You're fired, no reason to risk everyone else at the company. We don't want your type here. No public transportation too, so all the poor get to starve to death in their homes. As since we're checking your blood, we might as well compare it with all the unsolved crime cases and keep it on file just in case you do something later. Oh, is that a drug in your blood stream? Off to jail with you. Hmm, did you know 80% of people with that se

      • by bigpat ( 158134 )

        Of course, this is important for individual diagnosis. But it's the longer term implications on the epidemiology side that are absolutely huge.

        This seems to me to be the real benefit of these types of tests. I would hope that CDC, NIH in conjunction with other agencies would begin funding these types of tests on a randomized basis so they could see how viruses are spreading through the population and finding out how viral infections are interacting with other diseases and treatments. The data collection effort would be well worth it.

        The other test that has a similar implication was the one announced back in June This blood test can tell you ever [washingtonpost.com]

    • by tsotha ( 720379 )
      "Treat you? We don't really know what this one does. It might not be bad for you at all. Or it might kill you in some new and interesting way. Hard to tell."
      • We don't know what most viruses do yet. Detect them is the first step towards understanding what they do.

  • by iggymanz ( 596061 ) on Wednesday September 23, 2015 @08:43PM (#50586695)

    Trying to figure out the tech, reference was made to this

    http://www.google.com/patents/... [google.com]

    whereby for this particular application they have put "probes" for specific sequences of all known viruses on "tiles" of a rectangular area. In general, the tech could be used for RNA, DNA, proteins, and more

    • by Michael Woodhams ( 112247 ) on Wednesday September 23, 2015 @09:08PM (#50586791) Journal

      My understanding from a very quick skim of the paper (open access, here [asm.org]) is that they are not using microarrays. They have a mixture of a very large (2 million) number of probes to match DNA/RNA sequences of all known viruses which infect vertebrates. They use these to amplify viral sequences and then use normal high throughput DNA sequencing (Illumina, in this case) to see what they've got. They claim that it is sensitive to both DNA and RNA viruses (and all the variations - double, single stranded etc.) Being able to detect both DNA and RNA in a single test mildly surprises me, but I'm only slightly familiar with DNA sequencing technology, so maybe it isn't a big deal.

      They do say "A biotinylated oligonucleotide library was synthesized on the NimbleGen cleavable array platform and used for solution-based capture of viral nucleic acids present in complex samples containing variable proportions of viral and host nucleic acids." Perhaps that translates to say the microarray you talk about was used to make the 2 million probes.

      As a complete aside, I'm a little surprised this isn't a Nature or Science paper.

      • by gringer ( 252588 )

        They have a mixture of a very large (2 million) number of probes to match DNA/RNA sequences of all known viruses which infect vertebrates. They use these to amplify viral sequences and then use normal high throughput DNA sequencing (Illumina, in this case) to see what they've got.

        Yep, that seems a fair explanation. I liken it to trying to hit an ant with a minigun. It's probably not higher profile because probe capture has been done before (e.g. for ribosomal enrichment / exclusion); this is just taking it to the extreme. I wouldn't be surprised if someone follows this up later on with a 1 billion probe capture design for bacterial sequencing -- there'll always be more probes that can be added into the mix.

      • It is not a Nature or Science paper because it is just a standard target enrichment library. They've been doing this for a long time to profile things like cancer markers, disease panels, etc. These guys just made a library to target viruses. That's all. It can do both RNA and DNA because they do a reverse transcriptase reaction first (required anyway to sequence RNA), and then pull down the resulting cDNA along with DNA and sequence it. Kind of cool, but not really groundbreaking.

  • by Fwipp ( 1473271 ) on Wednesday September 23, 2015 @08:43PM (#50586701)

    In slightly more technical terms, they've designed a system that selectively targets & amplifies ~2 million DNA sites; chosen from the genomes of all known infectious viruses. The scientists basically apply this assay to the infected cells (I'm assuming they take a blood sample or something), leaving them with DNA that matches those targets. Then, they run those DNA fragments through a sequencer, and see what they got. From there, they can deduce which virus was present in the original sample.

    • by Iamthecheese ( 1264298 ) on Wednesday September 23, 2015 @08:56PM (#50586739)
      If you're testing for that many viruses any false positive is unacceptable. So what's the false positive rate?
      • by Anonymous Coward

        Does it matter? Test for them all, get your positives, then run a specific test on the ones that could cause the symptoms. Or am I missing something?

        captcha: nonsense

        • by MobyDisk ( 75490 )

          Suppose the false positive rate is 2%. The article says it detects 700 vriuses. 2% of 700 viruses is 14 viruses. 14 tests could require 14 samples: so 5 blood draws + 6 urine samples + 3 stool samples. Ugh! (And no - you can't usually run 2 arbitrary tests from one sample.) So to make this work, the doctors would have to look through the results to see which viruses match the symptoms, so they only run the specific tests for those. That is probably what happened in this example. They probably saw a

          • by Immerman ( 2627577 ) on Thursday September 24, 2015 @02:10AM (#50587665)

            You're ignoring the second half of their suggestion - test for the "detected" viruses that could cause the symptoms. If you had a 2% false positive rate, and 10% of the "viral library" your checking against could cause the symptoms, then you're averaging 2%*10%*700 = 1.4 false positives per patient.

            Of course RTFAing tells me that they're expecting no false positives at all thanks to the fact that this technique provides the complete genome of everything detected, as it occurs in the patient. It's not a "yes/no" like most current tests, or even a "70% certainty", it tells you that "this *exact* genome was in the sample", even if it's something that you've never seen before that was just similar enough to stick to one of the "hooks". You then look up the freshly-sequenced genome in your library to figure out what it is. False positives would imply that the replication system somehow managed to spontaneously create recognizable genomes from scratch.

            As I read it the methodology is:
            1) catch a wide range of "suspicious" viral DNA
            2) replicate it so that you can...
            3) sequence it all
            4) compare sequenced DNA to database to identify pathogens and unknown viruses.

            (1) will likely generate a fair amount of false positives, but unlike traditional tests at that point it's just bringing in "suspicious characters" for questioning. (2) and (3) should be pretty much immune to false positives, and (4) will give you a fully "fingerprinted" list of "confirmed-present" viruses, along with a confidence-rated identification of anything with a match in the database.

            • False positives would imply that the replication system somehow managed to spontaneously create recognizable genomes from scratch.

              A "false" positive could also mean that the virus is present, but not replicating at any real level of infection.

            • by MobyDisk ( 75490 )

              To set the record straight, I skimmed the article and missed the "no false positives" claim. Doh! But I am skepitcal of that claim. The article says:

              And since the technique offers up the full genomes of whatever virus it detects, it shouldn't throw up any false positives

              That's like me saying "because I showed my work, my answer cannot be wrong." Just because it gives the sequence of what it thinks it found, doesn't mean that it was actually present, and that the sequence is correct. I've worked on PCR systems, but never sequencing systems. Are they really 100% perfect? If so, then... wow... that's amazing.

              • by Fwipp ( 1473271 )

                They're not 100% perfect, but they're much much much more accurate than they need to be for this sort of analysis.

                For example; I picked out a sample mostly at random from an internal dataset. In this shallow sample of 4 million reads, over 90% of reads have all 36 bases with quality > 30. (Quality is in Phred score: q30 = the sequencer estimates a 99.9% chance that this base is read correctly). Even if 3-4 bases are incorrect, it's still usually possible to map the read to the genome with high confidenc

              • I'll admit I'm not even remotely well versed in the details of DNA replication and sequencing techniques, but I imagine a certain degree of error is inevitable - even properly functioning living cells are incapable of 100% accurate DNA replication (quite possibly by "design", but still.)

                It seems likely though that the nature of those errors would result in "bad reads"/"noise" in sections of the sequenced genomes, not the wholesale creation of genomes that weren't in the original sample to begin with. That

      • by wwalker ( 159341 )

        What?! False *negatives* would be unacceptable. If the broad test is less sensitive than the specific tests and often misses a lot of viruses, then what's the point of having a broad test? False positives are perfectly fine on the other hand. You can always run a specific test to confirm the results of a broad test. In fact that's how it works for a lot of conditions. You run a highly sensitive cheaper or less invasive test that's known to be imprecise and only then you confirm the result with a more compre

      • by AmiMoJo ( 196126 ) <mojo AT world3 DOT net> on Thursday September 24, 2015 @03:53AM (#50587819) Homepage

        A few false positives would be fine, you can just run other more traditional tests to rule them out. This sort of diagnostic is for people who have problems that cannot be readily diagnosed. The choice is either do many expensive tests for different and very unlikely viruses, or use this technique to narrow it down to a small field.

        You wouldn't start treatment on the results of this test alone, you would confirm them first.

  • So you're saying the labs will no longer be able to gouge us for a two dozen different tests on the same blood sample?

    • Only if all the tests were for viruses.

  • He's got a severely compromised immune system, and yet he goes to a 3rd World country.

    What am I missing here?

    • A couple of my relatives with AIDS visit the rest of the family in southeast asia without incident. That's common. Maybe you have some misconceptions.

    • by jedidiah ( 1196 )

      Yes. Quite. There are some things you can't avoid in that condition and others that should be easily avoidable.

      Although we still have to pick up the pieces after someone inflicts stupid upon themselves.

    • by skids ( 119237 ) on Wednesday September 23, 2015 @09:19PM (#50586833) Homepage

      Availability of $13 generics for drugs that cost $750 here?

  • Great test if it has good sensitivity and specificity. However, the problem will be that it will yield too much confounding information - the so called 'incedentaloma' but only for viruses. It will lead to people receiving unnecessary treatments for the things that were found. Should only be used for 'house' like cases where 'odd ball' causes are suspected.
    • by ColdWetDog ( 752185 ) on Wednesday September 23, 2015 @11:12PM (#50587209) Homepage

      Since we have very few antivirals, it isn't much of a problem.

      "Go home and wash your hands. Don't kiss anybody you like." And that's pretty much it.

      • Since we have very few antivirals, it isn't much of a problem.

        If I understand it correctly: When you have a sequence you can CONSTRUCT a specific antiviral for it.

        Better yet: You can also construct (or select off-the-shelf) antibodies to it, for antiseura treatment. That's very effective and blazingly fast for any infection that is accessible from the bloodstream.

    • by KGIII ( 973947 )

      Do you mean " incidentaloma [thefreedictionary.com]," perhaps? I was unable to find your word at The Free Dictionary or at the OED site. What does this have to do with finding a tumor without having exhibited signs or, basically, by accident? I'm assuming they'd not just be doing this sort of testing at random or anything but will be limiting its use to just those who appear to be suffering from viral infections. (Is it considered an infection if it is viral and not bacterial?)

      After the 'review' button, well, this reply looks as if

  • by GoodNewsJimDotCom ( 2244874 ) on Wednesday September 23, 2015 @09:15PM (#50586821)
    If this system finds all known human viruses in a person's blood, my guess is it has to put them there. How else can one person get all human viruses at once?
  • One step closer to a medical tricorder that tells you exactly what's wrong with your patient. Amazing.

  • So that all viruses that usually aren't seen in humans are added to the list of those possible to detect.

    I wouldn't be surprised if there are viruses that exists and spread without causing symptoms at all as well. It would be a good strategy for spreading - do it silently.

  • The New Technique That Finds All Known Human Viruses In Your Blood

    Well, not all, I hope. Otherwise I'm in trouble.

  • The way I've been feeling the last few days, I've probably got all known viruses in my blood.

  • They'll still get you with the annual definitions update subscription. Doesn't even have real-time detection - you have to do a full system scan when you suspect a virus.

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