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Phylogenetic analysis of MLV sequences from longitudinally sampled Chronic Fatigue Sy

Discussion in 'XMRV Research and Replication Studies' started by RedRuth, Aug 18, 2011.

  1. RedRuth

    RedRuth Senior Member

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    Phylogenetic analysis of MLV sequences from longitudinally sampled Chronic Fatigue Syndrome patients suggests PCR contamination rather than viral evolution. Abstract:

    This is an analysis of sequences from the Lo study.

    http://jvi.asm.org/cgi/content/abstract/JVI.00827-11v1
  2. free at last

    free at last Senior Member

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    Our freind Greg again, I wonder if Alter and low would agree with this. If so then case closed maybe. wonder if its worth sending them this for a comment ?
  3. WillowJ

    WillowJ Senior Member

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    Is there somebody besides the (bio)psychosocial school doing analysis on these?
  4. RedRuth

    RedRuth Senior Member

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    The authors are from


    Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK

    MRC Centre for Medical Molecular Virology, Division of Infection and Immunity,
    University College London, 46 Cleveland St, London W1T 4JF, UK

    Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

    Prof Kellam is an expert on viral genomics: Paul's laboratory investigates virus genetic variation and virus-host cell interactions. He is a Professor of Viral Pathogenesis at University College London.
  5. RedRuth

    RedRuth Senior Member

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    I'm sure they'll see it I wouldn't be surprised if they weren't advised of it before publication.
  6. currer

    currer Senior Member

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    I think what we lack here is the willingness to humbly look at what is found, with a desire to help the patient and understand the disease, and then to draw theories from this data.

    I am very suspicious of papers which presuppose the superiority of theoretical abstractions to reality and show no concern for the suffering of patients.
    The association of retroviruses with ME have been repeatedly blocked over the past twenty years.
    Negative papers have no difficulty getting published.
  7. eric_s

    eric_s Senior Member

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    We've known for 8 months or so that this is what these authors believe. Maybe they are right, maybe not. So it doesn't change much for me (haven't read it yet, though), unless Lo or Alter or some people i could consider neutral would change their minds.
  8. Deatheye

    Deatheye Senior Member

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    I think it is importand to note that they used the word "suggests" in the titel.
    There seems to be bether words if you are certain.
  9. Esther12

    Esther12 Senior Member

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    Some researchers do talk in a dismissive way of CFS... but I don't think it's fair to assume that those whose work challenges a link between XMRV and CFS are not concerned about the suffering of papers (not that you were doing that). Also - those who are uninterested in patients, and are solely concerned by an abstract interest in viruses could end up being in a better position to look dispassionately at the data than those who are more emotionally involved, and desperate to help the patients they've met.

    Surely we should be getting some data from the BWG soon? Didn't Mindy @ CFS central post something about them unblinding results a little while back? I'm not expecting XMRV to work out for CFS, but strong results from BWG or Lipkin would change that instantly.
  10. RedRuth

    RedRuth Senior Member

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    As an old colleague of mine used to say, proof is for alcohol and maths, if you want proof you've come to the wrong department. Scientists don't say anything much stronger than 'the data suggests'. What's important is the analysis.
    WillowJ likes this.
  11. RedRuth

    RedRuth Senior Member

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    They're just reporting their data interpretation, given that they've got an expert in viral genomics as an author, their interpretation has validity.
  12. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Not if it's plainly wrong. And certainly not if there is a pattern of being wrong that calls into question the competence or motives of the authors.

    "Nevertheless even rudimentary research reveals that HIV is the exception within the family of retroviruses rather than the rule. It is clear that HTLV does not behave in accordance with the assumptions inbuilt into Tower's mathematical model. HTLV can be transmitted through 3 generations and the virus in the grandaughter differs by only one base from the one in the grandmother.This means that the assumptions built into the Towers model are absurd. Another retrovirus LP-BM5 displays no sequence variation whatsover but induces horrible pathology. LP-BM5 is a gammatretrovirus. Thus only HIV is known to display the degree of longitudinal variation assumed in the Towers computer programme.Science can be defined as the belief in the ignorance of experts.It would appear that Towers and Coffin are are more ignorant than most. This is all very sad and potentially so dangerous to the human race as a whole.The other point is that recombination or frameshift mutations can produce sequences which a fundamentally different as in the case with LP-BM5. This is how a gammaretrovirus differs from a lentivirus. Polytropic modified polytropic and xenotropic viruses are virtually interchangeable" - jhk on mecfsforums.
  13. eric_s

    eric_s Senior Member

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    That's not exactly true, 8 months ago the same people said there's no XMRV in ME/CFS. They did not use that kind of language there, like "the data suggests". I don't feel like going back now and reading the exact wording they used back then, but if you do, you will see it.
  14. free at last

    free at last Senior Member

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    LOL Eric so true. when the DATA STRONGLY SUGGESTED that ME/CFS was associated with xmrv. wessly said he didnt expect to find it. biased analysis it seems Redruth. And Reeves too said the same he didnt expect to find it. regardless how persausive the intial science study was. No its not about what the data suggests. often its about what they think the data SHOULD suggest. and as for analysis. there interpretations. were clearly biased from the outset. dont forget this was the reaction right at the begining before anyone had even tried to replicate the WPIs work. Well im sorry thats proof enough for me Red ruth that eric is exactly right here. And like him i cant be bothered to find the exact qoutes. but that was the reaction from them. would like to point out Red ruth even coffin was impressed back then with what the data suggested. so not all so called scientists follow the lovely scientific codes its seems. As much as you would like to belive. If this doesnt prove it. i dont Know what does. But hey towers might be doing the same right now. he might be. might not. Hard to know in this fuzzy world called ME/CFS
  15. WillowJ

    WillowJ Senior Member

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    yes, and Wellcome Trust is unbalanced when it comes to ME, which is why we take them to be a part of the (bio)psychosocial school
  16. RedRuth

    RedRuth Senior Member

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    I don't know where you copied this from but whoever wrote it either hasn't read the paper or hasn't understood it. This isn't about the rate of evolution it's about working out the probabilities of Sequence A (taken at time point 1) being ancestral to sequence B (taken at time point 2, 15 years later). The maths is very complicated and I don't pretend to understand it entirely but the outcome is clear, it's extremely unlikey that that the sequence As are ancestral to the Sequence Bs, as they say The only realistic explanation that could account for these observations is that all of the MLV positive patient samples, or the PCR reactions performed using patient DNA as template, have been contaminated with mouse DNA. This would act as a source for amplification of the diverse viruses found . Basically the sequences represent different endogenous murine viruses.

    In fact they do talk about the rate of evolutionary change and note that it's possible for a retrovirus to evolve so slowly that some sequences will remain the same after 15 years but as they point out in one patient the change is zero and in others it's as vast as the diversity of that the whole set of known non-ecotropic MLV allows But as I pointed out, this paper is about phylogenetic relationships and the outcome is clear. Whoever you're cut and pasting from should actually read the paper before jumping to erroneous conclusions.
  17. In Vitro Infidelium

    In Vitro Infidelium Guest

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    The 'reference' is to another online forum where the prevailing attitudes are pretty well summarised by the quoted phrase Science can be defined as the belief in the ignorance of experts. It's difficult not to see this proposition as a call to embrace the Dunning-Kruger Effect as the descriptor of M.E/CFS activism. The attitude even has its own self defining logic - expert X has published material which is 'wrong' and with which 'we' disagree: therefore all experts with whom we disagree are wrong. There is also a supporting logic sequence which runs - expert X has been unkind/unhelpful to 'us': therefore we disagree with expert X (who is therefore wrong): therefore disagreement = untrustworthiness: therefore: expert Y who agrees with expert X is untrustworthy (repeat in infinte branching links as required).

    Saying 'science doesn't work like this' doesn't unfortunately break this line of thinking because "thats what experts say" and ....... Science can be defined as the belief in the ignorance of experts cue vapid commentaries about "appeals to authority' et etc etc. 'Sigh'.

    IVI
  18. currer

    currer Senior Member

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    Why cant there be different endogenous retroviruses in us?

    Because it would point the finger at the pharmaceutical companies and the virologists who said MLVs were safe to leave in pharmaceutical products.
  19. RRM

    RRM

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    I am really not here do debate the XMRV(/HGRV) hypothesis (I don't even have access to this paper ;) ), but there is something that I feel needs mentioning in the context of the discussion of this paper.

    With some experiments you could at least entertain the thought that scientists had been messing with the samples/data (although I personally don't subscribe to these ideas). However, even if you truly believe this to have taken place with some of the XMRV research, this study would still be a whole different ballpark.

    Why? Because all the experimental data that was used to do the analysis in the paper is freely available to everybody in the world.

    Remember, Lo/Alter, as well as the Lombardi team, performed phylogenetic analysis to substantiate their respective findings. The thing however with the Lo study is that Lo/Alter only performed phylogenetic analysis on the original samples. I am not critiquing this here by the way, as this choice was understandable: they retested the patients only after they found out about the conflicting CDC study. And because they felt the paper shouldn't really be held up any longer and the retesting results (apparently) confirmed their findings, they published their paper without doing a new analysis involving all of the found sequences.

    Now, Lo/Alter are still free to do this. Lo/alter have the means and knowledge to do so. Mikovits is also free to do the analysis on her computer(s), as well as Ruscetti or any other scientist you do consider to be trustworthy. Even Gerwyn or somebody from the forums can give it a try. If any of these people could show that these reported conclusions are faulty by simply running them through one of the many free phylogenetic computer programs of their own choice, this new study would be instantly regarded as a waste of space by the scientific community and the authours would be exposed as the incompetent/dishonest people that they then would be. It would be even worse for the authors if someone could show that the use of the same program (that was probably written way before the whole XMRV controvery) would or could produce very different results than these authors reported. And even if Alter/Lo/Mikovits or anybody else would "just" show that these results are ambiguous in the sense that only a very specific set of parameters could possibly lead to the conclusion that the old Lo/Alter sequences are ancestral to the newly found sequences, they would put serious doubt on the validity of this study.

    It therefore makes no sense to me at all that the authors of the paper here under discussion would/could produce faulty and/or fraudulent results that cannot be trusted.
  20. eric_s

    eric_s Senior Member

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    As far as i know they tested for mouse DNA at the Lo lab and found no contamination of that sort (or any other sort).

    Also, i find it hard to believe that Lo and Alter, who looked at these samples, the new ones and the 15 years old ones, would not have seen that the sequences in the older ones can't be ancestral to the newer ones. I just don't believe they would not be competent enough to do that analysis. Of course it's also hard to believe this British group is incompetent. The entire situation is hard to make sense of, as it has been all the time, since the publication of Lombardi et al. in 2009.

    Btw, even though this is not my forum and so this is only the personal opinion of one user, i think the effort to shoot down XMRV/MRV is getting a bit intensive on these threads for my taste now. I'm no scientist and i don't know who is right in this debate, as far as i'm concerned the jury is still out and i'm not even sure it will be case closed after the BWG, even though i hope it will be. But i think we need to keep an open mind and look at both sides and not call this to be over prematurely. Alter, Ruscetti, Silverman and many others still don't seem to think it's contamination they are looking at.
    WillowJ likes this.

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