Admin Posted November 19 Report Posted November 19 https://soundcloud.com/thedrnimanshow/11182024a1 You Good evening and welcome to the doctor Niman show today is Monday, November 18, 2 02 4. This is our next series of daily updates. Dr. Niman will now do his talk. Dr. Niman Thanks for tonight. I thought I would focus on the teenager and I kinda go through. How you can use the sequence to identify Where this virus came from in its recent past, and then I'll talk a little bit about the mutations and how they always can be used to to figure out how it got from entering British Columbia and ending In the ICU in the teenager The virus has most of the listers now it is in a teenager who's in critical condition and Went to the emergency room and got turned away at least once and Eventually got into admitted, and shortly after that, it was determined that the teenager had H 5 which then went to H5 and one in the sequence Came out over the weekend and I had put out some data today too, so that is a spoiler alert so if you don't wanna wait till the end that the virus actually came from wild birds, they probably even came from a cackling goose, and that wild bird was in British Columbia And the way you get to that is is using the sequence and Comparing with what other sequences are in the databases, there's a big database and she said, and most of the sequences get uploaded there from the various labs that get the samples and generate the sequence I meant this little earlier but for influenza it's a segmented genome so it's really eight different pieces and so full sadness to get a full sequence for All eight of those pieces and the full sequence is usually starting. It's usually covering the region that codes for the water or more proteins that are in there and and so you have a kind of a standard size that you can see out of the number of positions how many of those positions match that tell her what I put up the day I took the sequence from the teenager and. Ran the sequence for each of the eight segments and saw which sequences in the database matched the most closely and then put the top matches up on the On Twitter and a blue sky So just as a An example on how this is done your technically you can kind of just think of it out. It is a Google search and it's kinda like if you found a paragraph out of a book and you kinda knew it was a famous book and you knew the text to that book was probably. On the Internet in Google and search it, you could find that book by probably in both cases. You could take one sentence out of one paragraph and search that one sentence and you'll get a matched and they'll usually be. Unique match you're only gonna get one sentence at max is that Word for Word was this a very short sentence but it's the sentence with 10 or 15 words you're likely to get only one and One exact match and even if you're not get exact match, you'll have a pretty limited numbers that are close to that sentence and if you got the whole paragraph, you can either look at the sentences that are the top matches and see which one comes from a paragraph paragraph that matches the whole paragraph for you can go back and do the search account use five sentences and then you're guaranteed you're only gonna get one match and If that paragraph on the Internet, you're gonna get the whole paragraph and if you have the whole paragraph, it's probably in the book and you're gonna know where that satins are. Five sentences came from and you'll be able to do that identification so you do the same thing with the sequences of the virus The virus like I say is divide up eight pieces and so you can search each piece individually and The two that are really the simplest if you take the sequence for the MPG and that's got 982 positions and you take those 982 position from the teenager and you Basically put it into the search box and hit the search button and it'll kick back the top matches and a few seconds, and in the case of the teenager if you do that for the MPG out of all the sequences that are in the flu sequences that are in the database and that's gonna be I don't even know what it is for. I know what it is for for for Covid. It's like 17 million for fluid is it's it's probably less than that but flu in general it's gonna be hundreds of thousands and even eight. Five is gonna be tens of thousands of sequences and out of all of those sequences could be theoretically this isn't even a nature and this is an internal gene and all the flu. All the influenza. A sequences anyway will have will have an MTG and some of them be fairly close to this, even though. They may not be HI they may not be high path they couldn't even be but anyway the answer to the initial search there's only two exact matches so the two sequences at G said that exactly matched the MPG of the teenager in the hospital are To cackling, goose sequences, and there's information about each of these sequences that they go along with the actual name of the sequence add in this case The way influenza viruses are named is the first field is to type and these are all gonna be influenza so they all start with an a and then the second field is the species end of the case of the teenager since that a human species the species is an included that they can and I'll put in human or whatever you wanna Homosapien or whatever they just leave that field blank and they go right to the next field, which is the Location so in case of the geese there they're not human so the second field is cackling, goose and then the third Field is the location and these two castling geese. The location is BC for British Columbia and then you get to the actual number of the that's aside to the sequence and that's generally assigned for. By the lab that does the sequencing and I'll usually have a number and then they'll have some type of abbreviation that gives you an idea who the lab is and This one the letter is actually RAI D PH L and I would assume it stands for area influenza virus public health lab, which is what the lab in Columbia called to self and then what is the dash 253 5 The other one is 254 1 and they were both collected in last month and the last field this year and they both stay 202 4 that tells you from just that one search of One of the jeans that these are the top Canada, these these two sequences out of Hundreds of the house At least 100, 000 there's only two sequences that are exactly the same as the sequences in the teenager and there are two years that were from British Columbia and were collected last month. I mean the last month part is it in the name but the name is associated with meta-data. Which which lab did it who the scientist were when they actually collected it unfortunately with the with the teenager all it actually says it's November usually they keep the day and I'm not sure why they had trouble figuring out what day it was in November since it was deposited In November So they just got the sample a little while ago and they they should've known what day it was collected on, but they did not put that in and there's a lot of little things that are a little a little fishy about the The whole situation On these particular viruses but getting back to the next sequence and hold on one second here OK and then the next sequence was used as the NS sequence, which is a non- structural S stand for The MP action stands for matrix protein and in the case of the NST it's it has 238 positions and the Quence for the teenager again Came up with two sequences that were exact matches so they had 238 out of 238 of the positions and not surprisingly the two sequences that were an exact match for the N Were the same two cast duty geese so now it was Up to two out of the 18 were exactly the same in these cackling feast and then the next sequence that was done was the PB two sequence and let me get that from me and that case that the PP2 sequences Considerably bigger and The one cackling goose that was 253 5 Was the number one matched and that there was only one difference and it was it was 2 279 out of 2 2 80 so too much bigger jeans and there was only one difference between the cat one of the cat gees And then the one that came to number two was the other Kathleen juice and that match was 2 0 2,278 out of 2200 days so they're only two differences so they they were exact matches on to the jeans all by themselves and Now they were the top two for this larger team one had one difference and one the other had two differences. The next one that was done was the PB one Jane, which is also a big Jean and this time the other Catholic goose so this number 254 1. What's the top match? And again there was only one difference, though it was 2273 out of 2 27 4 and then the other cackling goose had two differences that goose was tied for second place there were there were three other wild birds that also had only Two differences and one was a snow goose one was a Canadian goose and one was another cat goose and I'm going to the next run. It was the polymerize a the P 18. And in that case 253 5 gas clean goose Was an exact match it was 2251 out of 2251 but that was shared with three other wild birds were exact match for the P 18 and then for the there were two that only had one difference and one of the two was the other cackling goose so the two cackling goose these one was exact one had a single difference And then going down to the H 5 Dean the They had three differences with the H 5 and they both had 17 oh one out of 170 4 so that was the three differences and they were tied there with Six other sequences that were also that close that they basically only had three differences and so they were among the most closely related to the key, but they were their brothers that were at that level and then Going to the next sequence was the N teaching as a nuclear protein and in that case both of these cackling gees were exact matches 1497 out of 149 7 and there were I'll see what would that be? There would be 10 others that also wear exact matches and those 10 others included five of the colors at the Franklin County. Layer farm in Washington state and five were wild birds and one was from a turkey farm. The wild birds and the turkey farm were off from British Columbia. And then the last one is the the N one And the one in this case it's the genotype is D one.1 and one.1 has a North American They are in one and so any any matches I gotta be with North American, wild birds, and the two Kathleen geese were again of the number one physician out of all the other sequences in the database and they both were 1406 out of 1410 so there were four differences, but that was the best and the sequence could do and the database and that was shared with one other Wildbird sequences and so The upside is that if you take all those matches, you'll see these two cast these were at the top of the list in And everyone of the 18 segments and that's a strong indication that this virus before it got into the team was in a wild bird almost certainly likely to be a cackling, goose almost certainly a wild bird And that's where it was when I came into British Columbia or evolved in British Columbia as the other part of the question is what happened to that goose Before the virus in the goose ended up in the teenager and there as I had mentioned yesterday that the sequence of the teenager has three very critical Changes and these to who them are changes that are widely studied as changes that Move the virus from being an alien virus to being out my mail virus and why does PB two change E2 80 627 K with the primary to be more most efficient at 33° C which is much closer to human than the bird temperature which is 41° C And if the Position didn't change to OK it would've been eating and he is is optimal at the same temperature. It's as a bird. It's at 41° seven grade and the other one is. E1 90 D and that's a keychain that kind of loops around him and comes in close contact with The other chain it has which is Q226 8 and position 2 26 and 228 are kind of the key positions and the reason they keep positions is The H5 are somewhat analogous to H2 circulating in wild birds and then it acquired those three changes the 1 22 62 2 8 and the eight and 62 7 and the PB two And that took That H2 from an avian H2 to a human H2 and led to a pandemic. The pandemic began in 1957 and started in Singapore and it ended when it was displayed by another pandemic, which was. The Hong Kong flew where it was originated in Hong Kong and the H2 that replaced by H 3H3 and two is the other seasonal that started as a pandemic back in 19 68 and the question is number one how easy is it to make those changes and the answer is it's not that hard to make the PB two change but it is hard to make The two changes on the H5 and the reason it's hard is I'm the only have to change one of the three nucleotides in the codon for position 1 90 are the same thing for position 22 6 but the change that you have to make to go from Adrian to my mail is what referred to as a transversion and just briefly to think about the model biology kind of background / Genetics the the virus is actually have RNA but the difference between an RNA and DNA is is just one of the letters a T is in DNA and you was an RA But they have the same base pairing the keys or use pair up with a and then like I said there's only four letters so it turns out to the four letters represent two different types, appearing in a remedy and For the DNA to form a nice double helix they They the pairing up rules, always pair up with one pairing with one perimeter, and in this case, these transfer since kind of breaks that rule that they come up with another Another letter that that ends up either having to purines at the position or to perimeter at the position and that all the way that genetic code is set up It harder for that to happen and it really doesn't I'm not gonna go to the details as to why it's easier while it's hard but trust me that the two trans versions are much rare than the new permitting for perimeter or appearing for pure color. Transition transitions are a lot easier and the PB twos the transition and the two changes in the H fiber transversions so. The time just calling, you know that level of detail, it would be very unlikely that all three of these changes would happen to the teenager between the time The teenager was infected, and the time they collected the samples and is much more likely that these three male changes evolved in other mammals before they got out of the teenager and So there is the story that the family dog was was ill and had to get put down. It seems that the prevailing story now is right about the time the team developed symptoms and they initially tested the dog and it was negative. But as I said yesterday, the virus sometimes could move by the time they they got to get a sample from the dog. He was probably in while it was right before he was he was put down, so the dog would've been very ill and is very possible that the virus was in the dog salon, causing serious problems and it already been cleared from the dog nose when he got first infected, which is probably many days before the sample is collected. As the nose may be negative, but that doesn't mean that there's not virus in the lungs and it doesn't mean there wasn't virus in the dog nose when he was getting sick and was Probably in close contact with the teenager that's in the hospital now, but it's not even clear that that would be enough just to go through one mammal so it could very well be that that the dog ended up getting affected from some other mammal that eats Wild birds like a possum I don't know if you did that but other carnivores would would Feast on a bird and could get infected and that could've caused some of the changes to happen in that mammal and that more changes happened in the dog and then The team got infected and has these three very rare you take sense so it's a concern because of the origin it was in the wild birds and probably not that many wild birds are flying around with all three of these changes but There can be other other mammal certified cut us had a similar situation or somehow I had A mammal to mammal transfer that Ended up, causing other humans to be affected now How transmissible this virus would be yeah In the eighth, it's only got one of the two that that make it very transmissible, but it's probably more transmissible than The virus doesn't have the changes that are in most of the wild birds, but it is an example that that this is already happened once and there are a lot of wild birds that are that are going through the area out there that they basically spent the summer up and In Canada, probably northern Canada or Alaska and they breed it over the summer and then when the the newborns are ready to fly, they they go they head south for the for the winter and that's what's going on right now and unfortunately, it's not just in the Pacific flyway, the Pacific flyway is getting a lot of Positive farms now both in British Columbia and now starting to pick up in Alberta first case went back once confirm today And I think there's one that says Saskatchewan rather than any event they're heading south. They're starting to show up in other flyways in the United States also. Right now there's more activity in the Pacific fly away. It's gotten all the way down to Arizona now there's a lot in California. They were there a number of poultry farms that were announced today. In California, it's a little bit confusing it with the virus. It is because they've got the beef free at 13 which is the dairy farm one and those numbers are going up very dramatically. I think there was something like 40 farms that were identified since Friday. And they're up to I think there's 11 00 dairy farms in California. There's the number one built. Pretty sure the country in about 30% of now have been infected with the B31 3 and when there's a lot of that that virus present there is spill over isn't just the Gary fire to virus. Manages to get from the dairy farms to the poultry farms and that's primarily done Small animals like nicer cats can get affected as far as mammals are concerned then the various small birds like sparrow or starling or pigeons Can get infected and they're smaller so that even if there's some type of Barrier to try to keep the wild animals out they have an easier time getting in and they frequently go inside to get to the to get to the food and they get to the food deal Defecate into the food and then the cow eat the food or the chickens or turkeys. I'll eat the food and then they'll get affected with the with the same virus that in this case get affected with the virus it's normally found in the dairy so that's gotta wrap it up for tonight it's just a little bit of molecular biology and. The main point is you can tell a lot of information from the sequence and I've always maintained the stories in the sequence and in this case you can get the origin you could see how complex it changes are and you have a better idea of why the teenagers in the ICU You OK, the information will continue to do these as time permits. Everyone have a great evening.
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