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XMRV complete proviral genome, isolate S-162

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Jun 21, 2011.

  1. Jemal

    Jemal Senior Member

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    New XMRV sequence posted to Genbank on 10 june, by the Lithuanians.

    Tried to quote something, but it became a mess. Check the link.
    It's probably relevant, because it claims to be complete?

    More:
    http://www.ncbi.nlm.nih.gov/nuccore/FR872816.1

    edit: I said Ukrainians first, but they are Lithuanians.
     
  2. Jemal

    Jemal Senior Member

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    A study might be published as well? The title seems to hint at that.

    And because they posted this sequence, it's probably positive?
     
  3. eric_s

    eric_s Senior Member

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    I've run BLAST and it seems to be very similar to already published sequences, but don't take my word for it.
     
  4. Jemal

    Jemal Senior Member

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    One day I am going to learn how to do a BLAST :D
     
  5. kday

    kday Senior Member

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  6. Bob

    Bob

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    I did a BLAST for FR872816, the new XMRV sequence.

    I'm not an expert on the system, so I might have done it incorrectly, but these are the results i got:

    It says the whole genome is 99% max identical to VP62

    gag gene 97% max indentical to VP62

    env gene 94% max identical to VP62



    Then I did a BLAST for some of Switzer's recent sequences

    gag gene was 98% max identical to VP62

    env gene was 94% max identical to VP62

    I don't know how significant these percentages are, except to say that Switzer said that his sequences were evidence of normal human infection and transmission.


    BLAST is here if anyone wants to have a go:
    http://blast.ncbi.nlm.nih.gov/Blast...astSearch&SHOW_DEFAULTS=on&LINK_LOC=blasthome
     
  7. eric_s

    eric_s Senior Member

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    It's not difficult, all you need to do is one or two clicks. The difficult part is to know what to make of the result ;)
     
  8. kday

    kday Senior Member

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    So here's my thoughts:

    - XMRV will be seen as a human pathogen
    - XMRV will be associated with prostate cancer

    This new sequence shows quite a bit of variation in my opinion, and I don't think the contamination theory will be able to explain this one away. However, I think XMRV will be seen as both a lab artifact and human infection. I think scientists will have a lot of trouble agreeing that a retrovirus created in a lab caused human disease (that's if they agree it causes prostate cancer), so I think we will see alternate theories as well that sound more natural (Perhaps someone was bitten by a mouse in the woods of another country? :D).

    I think there will be continued skepticism on whether XMRV is associated with and has infected CFS because the contamination theories and because the WPI sequences look as if they could be contamination (VP62).

    However, I think there might be more attention to XMRV/CFS when more positive XMRV/CFS papers are published (they are coming). Perhaps scientists will watch and wait for the BWG/Lipkin results before they jump on the bandwagon again.

    I'm not sure what the results of the BWG/Lipkin studies will be. The WPI still displays a lot of confidence, so perhaps they are right. I would think they would have taken the extra time to make sure they can tell the difference between a patient and a control in a blinded fashion by now. Maybe not. I don't know. If they are right, I think most in the research community would be very surprised.

    Then if CFS patients are infected and if they determine it plays a role in CFS, they would have to determine if it's the cause. It will be war all over again.

    If there is a CFS/XMRV connection, there will still be a long road ahead (unless everyone fears the virus for some reason as with HIV). Perhaps scientists will rush to solve it out of fear of them being infected.

    Just some random thoughts as I try to deal with insomnia. In the mean time, with the recent news that concludes XMRV definitely does not play a role in CFS, we will start to repeat history and go back to Ampligen trials (oh, right that's already being done).
     
  9. jace

    jace Off the fence

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    This is a full proviral sequencing of XMRV, the first one published.

    The naysayers, Coffin, Stoye, et al have made a huge noise about the lack of XMRV sequence variations published in Genbank, and they say that this 'proves' contamination. How that links with the Lo/Alter findings, where sequence identity between the virus fragments they found and XMRV, about 87%, which the naysayers (as before) said were not XMRV because they were too different? Who knows. They want their cake and eat it too. FYI the various strains of HIV have an 85% sequence variation.

    Lately the cry has been "published XMRV sequences are all too identical to be a wild virus". Well, now we have published a strain with 95% sequence diversity, which kinda shoots that idea dead.
     
  10. eric_s

    eric_s Senior Member

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    I am totally unable to say wheter this new sequence is an argument for or against contamination, but i don't see the 95% diversity. I think one has to look at the entire genome and not just one part. If there was only one nucleotide or base or base pair or whatever we are looking at here in the entire virus that was different from VP-62, and you looked at only that you would have 0% identity, even though the entire virus would be more than 99% identical. So i think for this sequence, to be fair, we would have to call it 99% identical (with a query coverage of 99%). If that's the same for Switzer's sequences and he says they can't be explained by contamination that's an interesting point. But i really fear i'm only adding to confusion and misinformation by speculating about these things.
     
  11. kday

    kday Senior Member

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    There is a 95% number on a blast below the table. Somebody told me that was the number to look at. I really don't know, but I don't understand how you would get 99% when all the regions show quite a bit of diversity.

    And the phylogenetic tree looks a lot different than the WPI sequences. When you compare these to the WPI sequences they look a lot different. From my eyes the sequence does not resemble VP62, but I guess I need to get a virologist to comment (and I am trying).

    And remember, we are looking at prostate cancer, not ME/CFS.
     
  12. anciendaze

    anciendaze Senior Member

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    A long time ago, in Internet terms, I described how the algorithms for sequence comparison first came into existence, and how various rules of thumb used by researchers got coded into programs, here. Coding an assumption into a program may hide it from all but a select few, it does not make it more than an assumption.

    Hidden in that post is a prediction that, until we have this virus well-characterized, every new sequence will produce a different phylogenetic tree.
     
  13. eric_s

    eric_s Senior Member

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    I looked at this screenshot you provided: http://i.imgur.com/s1yky.png.

    If i understood it right this was the result of a BLAST run comparing the entire new sequence to other sequences in the database.
    The result said "Query coverage: 99%" and "Max ident: 99%" for VP-62. So i understand it this way that BLAST compared either 99% of the new sequence to VP-62 or 99% of VP-62 to the new sequence and in this comparison found that they are 99% indentical. But that's just my interpretation without ever reading up about how blast actually works. So take it with some caution...

    I don't know how you got the 94% here: http://i.imgur.com/wpnsq.png. Probably you compared a region of the new sequence to VP-62. But i think when they talk about percentages and similarity they usually talk about the entire genome, not just a region.

    About the phylogenetic tree i can't say anything, i have no idea about these things. I don't say this new sequence stems from contamination, don't misunderstand me. Actually i never supported the contamination hypothesis. I only said that i don't think this new one is only 95% identical to VP-62.

    It would be great if you could get a virologist to comment.
     
  14. omerbasket

    omerbasket Senior Member

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    It's a wierd thing there: In the table, it says that those are 99% identical, with a 99% query coverage. But when you click the link there, and it takes you to see how exactly it's aligned, all of a sudden you see down on that page that these are just 95% identical, with quite a bit of changes in the base pairs. I don't understand this system either, but unless someone here understands it perfectly, I think it would be wrong to conclude that those sequences (the lithuanian one and VP62) are 99% idnetical to one another.
    Anyway, here we have another study which seems to have found XMRV in prostate cancer - again, something that would make Coffin's argument (that XMRV is a contamination from 22Rv1) weaker. Also, I find it interesting - if that strain is indeed "just" 95% identical to VP62 - that they are calling it "XMRV", and the Lo/Alter strains, which are 84%-96% identical to VP62, mainly 94%-95% identical to it, are still being called by another name. I understand that there is this phylogenetic tree thing, but I don't really understand how it works and what it says, and I also don't know whether it is "stronger" than the percentage of similarity in the strains.
     
  15. Bob

    Bob

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    Yes, it's all very confusing, and it's even more confusing when BLAST tells us that totally different MLV viruses are 99% identical to XMRV!

    e.g. Why is Moloney Murine Leukemia Virus 99% identical?

    And one of the BLASTs that I did said this S-162 new sequence is 100% identical to mouse DNA, with 100% query coverage!

    I don't understand BLAST.
     
  16. eric_s

    eric_s Senior Member

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    Thanks. What i wonder is why does he call 96% identical "not very close", when in HIV there is more diversity than that?
     
  17. kday

    kday Senior Member

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    HIV mutates like crazy....
     
  18. omerbasket

    omerbasket Senior Member

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    Again, perhaps Miller would explain why strains of HIV-1 which are only 85% identical to each other, and strains of HCV which are only 79% identical to each other, are named HIV-1 and HCV.
    Besides, here you have scientist from lithuania saying that it's XMRV, and a scientist from the USA that seems to be invested (not in money, but in reputation) in the idea that XMRV is a contamination, saying otherwise. Why should we take Miller's word and not the word of the lithuanian scientists?
     
  19. kday

    kday Senior Member

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    We haven't heard from these scientists yet. I don't take one man's word, but I like to hear everyone's opinion. Hopefully more to come.
     
  20. Jemal

    Jemal Senior Member

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    XMRV or not, we humans seem to harbour an awful lot of mouse retroviruses ;)
    Somewhere along the line this can't all be explained by contamination anymore, I think. It's like the boy crying "Wolf!" all the time. There comes a time when that doesn't work anymore...

    Anyway, Miller might have published some research some of us don't look favourably upon, at least he is responding to questions.
     

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