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jbloom_lab's profile
Bloom Lab
Bloom Lab
Bloom Lab
@jbloom_lab

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Bloom Lab

@jbloom_lab

Lab studying molecular evolution of proteins and viruses. Affiliated with @fredhutch @HHMINEWS @uwgenome.

Seattle, WA
research.fhcrc.org/bloom/en.html
Joined June 2014

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    Bloom Lab‏ @jbloom_lab Jun 22

    In a new study, I identify and recover a deleted set of #SARSCoV2 sequences that provide additional information about viruses from the early Wuhan outbreak: https://www.biorxiv.org/content/10.1101/2021.06.18.449051v1 … (1/n)

    2:09 PM - 22 Jun 2021
    • 2,746 Retweets
    • 6,075 Likes
    • 𝓜𝓲𝓻𝓮𝔂𝓪 𝓓𝓲𝓮𝔃 😊 Josef Svenningsson Julien Limenitakis awe reminds u to wear double mask MFoxhunter bOta Michael Buckley ScienceStop xi jingping
    204 replies 2,746 retweets 6,075 likes
      1. New conversation
      2. Bloom Lab‏ @jbloom_lab Jun 22

        Specifically, NIH maintains the Sequence Read Archive, where scientists around world deposit deep sequencing data for others to analyze. I noted https://peerj.com/articles/9255  lists all #SARSCoV2 data in archive as of March-31-2020. Most from a project by Wuhan University. (2/n)pic.twitter.com/9V4dchZVUl

        9 replies 180 retweets 717 likes
        Show this thread
      3. Bloom Lab‏ @jbloom_lab Jun 22

        But when I went to Sequence Read Archive, I found entire project was gone! (Note that as detailed below, this does *not* imply malfeasance by NIH. Sequence Read Archive policy allows submitters to delete by e-mail request.) (3/n)pic.twitter.com/fEzOaVYZLZ

        9 replies 159 retweets 648 likes
        Show this thread
      4. Bloom Lab‏ @jbloom_lab Jun 22

        I was able to determine deleted data corresponded to a study that partially sequenced “45 nasopharyngeal samples from [Wuhan] outpatients with suspected COVID-19 early in the epidemic“ https://www.medrxiv.org/content/10.1101/2020.03.04.20029538v1.full … (4/n)

        3 replies 163 retweets 662 likes
        Show this thread
      5. Bloom Lab‏ @jbloom_lab Jun 22

        I discovered that even though the files were deleted from archive itself, they could be recovered from the Google Cloud at links like https://storage.googleapis.com/nih-sequence-read-archive/run/SRR11313485/SRR11313485 … (5/n)

        11 replies 154 retweets 907 likes
        Show this thread
      6. Bloom Lab‏ @jbloom_lab Jun 22

        Using this approach, I recovered files for the 34 early samples that were virus positive. I was able to use the data in the files to reconstruct partial viral sequences (from start of spike to end of ORF10) for 13 of these samples. (6/n)

        5 replies 123 retweets 742 likes
        Show this thread
      7. Bloom Lab‏ @jbloom_lab Jun 22

        Now I need to give background to explain a confusing scientific mystery about other early #SARSCoV2 sequences. Although events that led to emergence of #SARSCoV2 in Wuhan are unclear (zoonosis vs lab accident), everyone agrees deep ancestors are coronaviruses from bats. (7/n)

        4 replies 114 retweets 677 likes
        Show this thread
      8. Bloom Lab‏ @jbloom_lab Jun 22

        Therefore, we’d expect the first #SARSCoV2 sequences would be more similar to bat coronaviruses, and as #SARSCoV2 continued to evolve it would become more divergent from these ancestors. But that is *not* the case! (8/n)

        6 replies 228 retweets 866 likes
        Show this thread
      9. Bloom Lab‏ @jbloom_lab Jun 22

        Instead, early Huanan Seafood Market #SARSCoV2 viruses are more different from bat coronaviruses than #SARSCoV2 viruses collected later in China and even other countries. @lpipes @ras_nielsen give nice technical analysis at https://academic.oup.com/mbe/article/38/4/1537/6028993 … (9/n)

        7 replies 207 retweets 821 likes
        Show this thread
      10. Bloom Lab‏ @jbloom_lab Jun 22

        The conundrum is easily seen by plotting the relative differences from the bat coronavirus RaTG13 outgroup versus collection date for early #SARSCoV2. See how the first reported viruses from Wuhan (leftmost blue points) aren’t the closest to RaTG13. (10/n)pic.twitter.com/YuVp4efUNq

        11 replies 165 retweets 616 likes
        Show this thread
      11. Bloom Lab‏ @jbloom_lab Jun 22

        Same result if we use other bat coronaviruses like RpYN06 or RmYN02. To see this, go to https://jbloom.github.io/SARS-CoV-2_PRJNA612766/deltadist.html … for an interactive plot that allows you to select the bat coronavirus outgroup and mouse over points for strain details. (11/n)

        3 replies 70 retweets 430 likes
        Show this thread
      12. Bloom Lab‏ @jbloom_lab Jun 22

        How do deleted sequences I recovered relate to this conundrum? If we include those sequences, and note 4 sequences from Guangdong are from two groups of people infected in Wuhan in late Dec / early Jan, we get plausible scenarios that resolve above problems. (12/n)

        1 reply 82 retweets 482 likes
        Show this thread
      13. Bloom Lab‏ @jbloom_lab Jun 22

        These two scenarios are plotted below. Each has a different “progenitor”, which is the sequence that gave rise to all *currently* known #SARSCoV2 sequences (still may not be virus that infected patient zero if other early sequences remain unknown). (13/n)pic.twitter.com/3k7eHrgNgf

        9 replies 114 retweets 521 likes
        Show this thread
      14. Bloom Lab‏ @jbloom_lab Jun 22

        Both putative progenitors have 3 mutations relative to Seafood Market viruses that make them more similar to bat coronavirus. One is progenitor inferred by @kumar_lab @sergeilkp et al (https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msab118/6257226 …), other has C8782T, T28144C, and C29095T relative to Wuhan-Hu-1. (14/n)

        4 replies 87 retweets 442 likes
        Show this thread
      15. Bloom Lab‏ @jbloom_lab Jun 22

        Both progenitors suggest #SARSCoV2 was circulating in Wuhan before December outbreak at Huanan Seafood Market, which is corroborated by lots of other evidence, including news articles from China in early 2020 (see intro to my paper linked in first Tweet in this thread). (15/n)

        11 replies 284 retweets 993 likes
        Show this thread
      16. Bloom Lab‏ @jbloom_lab Jun 22

        There are also broader implications. First, fact this dataset was deleted should make us skeptical that all other relevant early Wuhan sequences have been shared. We already know many labs in China ordered to destroy early samples: https://www.scmp.com/news/china/society/article/3084635/china-confirms-unauthorised-labs-were-told-destroy-early … (16/n)pic.twitter.com/ajtm8SxfVu

        10 replies 306 retweets 1,182 likes
        Show this thread
      17. Bloom Lab‏ @jbloom_lab Jun 22

        Sequence sharing could be further limited by fact that scientists in China are under an order from the State Council requiring central approval of all publications: https://apnews.com/article/united-nations-coronavirus-pandemic-china-only-on-ap-bats-24fbadc58cee3a40bca2ddf7a14d2955 … (17/n)pic.twitter.com/rGwfFUONTn

        2 replies 119 retweets 635 likes
        Show this thread
      18. Bloom Lab‏ @jbloom_lab Jun 22

        Second major implication is that it may be possible to obtain additional information about early spread of #SARSCoV2 in Wuhan even if efforts for more on-the-ground investigations are stymied. (18/n)

        2 replies 97 retweets 555 likes
        Show this thread
      19. Bloom Lab‏ @jbloom_lab Jun 22

        Scientific communication and data sharing typically rely on trust. The NIH Sequence Read Archive has >13,000,000 runs, so they have to trust authors when they request deletions as not feasible to validate reasons for all requests, some of which are legitimate. (19/n)

        2 replies 64 retweets 474 likes
        Show this thread
      20. Bloom Lab‏ @jbloom_lab Jun 22

        In case of data set I describe above, it seems possible that trust that the NIH Sequence Read Archive grants to scientific authors to delete data may have been used to obscure sequences informative for understanding early #SARSCoV2. (20/n)

        2 replies 95 retweets 535 likes
        Show this thread
      21. Bloom Lab‏ @jbloom_lab Jun 22

        Fortunately, Sequence Read Archive has rigorous data tracking enabling them to determine when data deleted & stated justification by authors. In fact, @NIHDirector @NCBI have already determined this & generously shared info w me, but will let them share more widely. (21/n)

        7 replies 78 retweets 563 likes
        Show this thread
      22. Bloom Lab‏ @jbloom_lab Jun 22

        It is important to examine if other trust-based systems in science conceivably may have also been used to hide data relevant to origins / early spread of #SARSCoV2. This includes not only looking more at sequence databases, but also paper reviews, grant reporting, etc. (22/n)

        3 replies 110 retweets 611 likes
        Show this thread
      23. Bloom Lab‏ @jbloom_lab Jun 22

        Third major implication is that scientists need to stay focused on data-driven study of #SARSCoV2 origins / early spread. After spending the last 4 months studying this closely, I am cautiously optimistic that additional relevant data are still likely to come to light. (23/n)

        1 reply 99 retweets 680 likes
        Show this thread
      24. Bloom Lab‏ @jbloom_lab Jun 22

        We should therefore avoid dogmatic arguments about #SARSCoV2 origins / early spread, and instead focus on following two questions: (1) How can we get more data? (2) How can we better analyze the data we have? (24/n)

        13 replies 172 retweets 1,077 likes
        Show this thread
      25. Bloom Lab‏ @jbloom_lab Jun 22

        Finally, my analysis is on GitHub at https://github.com/jbloom/SARS-CoV-2_PRJNA612766 … where you can access all code, data, & paper drafts. All updates are via time-stamped commits. This ensures transparency/reproducibility of this study are not in doubt, regardless of your views on interpretation. (25/n)

        41 replies 224 retweets 1,344 likes
        Show this thread
      26. Bloom Lab‏ @jbloom_lab Jun 22

        Bloom Lab Retweeted Bloom Lab

        https://twitter.com/jbloom_lab/status/1407542296497688580 …

        Bloom Lab added,

        Bloom Lab @jbloom_lab
        A short addendum to my pre-print on early Wuhan #SARSCoV2 sequences deleted from the Sequence Read Archive (https://twitter.com/jbloom_lab/status/1407445604029009923 …), courtesy of an anonymous Twitter user. (1/n)
        Show this thread
        22 replies 34 retweets 247 likes
        Show this thread
      27. End of conversation

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