Don't Blame Birds for 1918 Flu

[gsgs]

Re: Don't Blame Birds for 1918 Flu

when did that reassortment happen, which segments, how do they conclude that, just from the TMRCA-estimates ?

Can we make a chart like the one in my erlier post for each segment separately ?
Where did SW/31 come from,

does someone understand table 1 ?
what's "nodes"
do they claim all human H1N1 descended directly from BM18
in 2,3,5,6 but from human flu in the other segments with
reassortments in ~1910,1913,1911,1915 (expectation value) ?
the years in brackets give their 95% confidence interval ? ---edit: yes, 95%,
they call it Bayesian credible interval(BCI)----------

do they claim classical swine (e.g. SW/31) descendd directly
from BM18 in 1,7,8 but from another virus(es) in 2,3,4,5,6
with reassortment between 1918 and 1931 ?

what's TMRCA of one virus (BM18), node 2
what's swine/human in node 1, they didn't mix after 1918, did they


March 31, so it was written (sent) before ****** was known.
Then it took >3 months until we hear about it

It's basically a new program to estimate TMRCAs which uses new methods
which reamin unclear. Then the table 1 which it produced and an
accompanying test to declarify the issue ;-)

-----I keep editing this----

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

pre-existing human viruses and newly introduced bird viruses
in the years before 1918 should be very different, or not ?
could they have been so similar that we hardly can distinguish them

when these exchanges with birds are so rare
(only 2 times in 1918-2009 in humans, never 1918-1976 in swine)
can we reasonably assume that it happened multiple times
in 1900-1918 ?

1910,1911,1913,1915


so 2,3,5,6 came directly from birds in 1918 or in 1914,1914,1909,1913 ?

WS33 and Melbourne/35 are rather close to BM18 in 2,3,5,7,8 especially 2
4,6 are hard to tell because of increased mutation

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

turkey/Ontario/6118/1968(H8N4) differs from BM18 by
102,085,080,430,126,345,052,035 promille
suggesting a TMRCA of ~
1907,1915,1918,1650,1892,1700,1918,1918

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

I don't see this 2356 reassortment involving BM18 and some early human virus
I don't see this 178 reassortment involving BM18 and some early swine virus.

They should be able to name these 2 viruses, that show the reassortments

two parents and one child please, for each claimed reassortment


I do see somehow 23578(46?) BM18+x --> WS33

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

AT-score in the 8 segments

BG75,5425,5646,5681,5820,5283,5644,5122,(5620),-2280,2274,2151,1687,1497,1380,982,838,>A/bluegoose/WI/711/1975///
BT77,5442,5659,----,----,----,5664,5112,----,-2280,2274,   3,   3,   3,1393,982,  3,>A/blue-wingedteal/ALB/286/1977/08/10/
DK74,5500,5642,5648,5870,5190,5587,5081,(5632),-2280,2274,2151,1688,1497,1387,982,838,>A/duck/Memphis/546/1974(///
MD79,5438,5637,----,----,----,5830,5162,5441,-2280,2274,   3,   3,   3,1396,982,838,>A/mallardduck/ALB/663/1979/08/13/
PT79,5456,5668,5564,5812,5223,5720,5203,5441,-2280,2274,2151,1693,1497,1395,982,838,>A/pintailduck/ALB/628/1979/08/13/
TK68,5429,5584,5611,5801,5190,5578,5112,5560,-2280,2274,2151,1684,1497,1400,982,838,>A/turkey/Ontario/6118/1968///
TK66,5482,5628,----,5826,5203,----,5061,5477,-2280,2274,   3,1687,1497,   3,982,838,>A/turkey/Ontario/7732/1966///
---------------------------------------------
     5453,5638,5626,5826,5218,5670,5122,5480


BM18,5561,5659,5620,5802,5310,5751,5152,5465,-2280,2274,2151,1701,1497,1410,982,838,>A/BrevigMission/1/1918(H1N1)
WS33,5596,5769,5699,5820,5317,5594,5295,5501,-2280,2274,2151,1701,1497,1362,982,838,>A/Wilson-Smith/1933(H1N1)
SW31,5561,5708,5676,5784,5310,5872,5162,5477,-2280,2274,2151,1701,1497,1410,982,838,>A/swine/1931(H1N1)
JB42,5578,5681,5639,5778,5310,5808,5142,5477,-2280,2274,2151,1701,1497,1410,982,838,>A/swine/Jamesburg/1942(H1N1)

QH05,5543,5716,5615,5856,5230,5614,5203,5613,-2280,2274,2151,1687,1497,1350,982,823,>IndexQinghai
KS07,5820,5897,5834,5812,5384,5865,5366,5596,-2280,2274,2151,1698,1497,1410,982,838,>A/Kansas/UR06-0068/2007(H1N1)
TX07,5732,5760,5741,5770,5450,5673,5254,5823,-2280,2274,2151,1674,1497,1380,982,838,>A/Texas/UR06-0356/2007(H3N2)
MX09,5526,5800,5578,5920,5377,5794,5285,5608,-2280,2274,2151,1701,1497,1410,982,838,>A/Mexflu/index/2009-02-01
LA87,5697,5778,5774,5776,5490,5964,5254,5704,-2280,2274,2151,1674,1497,1395,982,838,>A/duck/LA/17G/1987///

5570,5677,5639,5843,5323,5751,5203,5429,-2280,2274,2151,1701,1497,1410,982,838,>A/Index-of-these-3
5614,5791,5718,5802,5359,5800,5213,5501,-2280,2274,2151,1701,1461,1405,982,838,>Index-of-early-swine+human
5561,5659,5620,5802,5310,5751,5152,5465,-2280,2274,2151,1701,1497,1410,982,838,>IndexbiasedtowardsBM
5618,5779,5708,5796,5344,5737,5203,5465,-2280,2270,2151,1701,1497,1410,982,838,>Index,2k
5543,5716,5615,5841,5230,5614,5203,5613,-2280,2274,2151,1681,1497,1350,982,823,>IndexQinghai
5561,5659,5620,5802,5310,5751,5152,5465,-2280,2274,2151,1701,1497,1410,982,838,>A/BM18n
5592,5760,5708,5778,5357,5716,5213,5453,-2280,2274,2151,1701,1497,1410,982,838,>A/Index/earlyhuman
5592,5703,5685,5837,5317,5829,5152,5465,-2280,2274,2151,1701,1497,1410,982,838,>A/Index/earlyswine
5526,5800,5578,5920,5377,5794,5285,5608,-2280,2274,2151,1701,1497,1410,982,838,>A/Mexflu/index/2009-02-01
5728,5809,5867,5937,5384,5858,5203,5513,-2280,2274,2151,1701,1497,1410,982,838,>A/swine/Tennessee/25/77(H1N1)
5552,5642,5592,5759,5217,5574,5091,5489,-2280,2274,2151,1646,1497,1385,982,838,>A/fowl/Dobson/1927(H7N7)

so BM18 in 2,3,7,8 are much avianlike, similar to related avian viruses
in 1,5 is looks more mammalean
4,6 are special, wrt. AT-scores

so, this reflects the differences of the avian relatives in the segments
and supports the theory of reassortment of BM18 after avian introduction,
while 2,3,7,8 were still avian and introduced shortly (<10 years) before the pandemic
from relatives

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

promed:

http://www.promedmail.org/pls/otn/f..._BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,78360
---------------------------------------
If they are right, that suggests those viruses were all circulating
during the 1918 pandemic, which could explain uneven patterns of
disease seen at the time
-----------------------------------------
Taubenberger remains skeptical
----------------------------------------
likely to remain controversial. - Mod.CP]
---------------------------------------

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

no Super flu on weekends ?

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

no Super flu on weekends ?

Just needed some coffee! I'm back....

So what did I miss.

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

promed reply:

http://www.promedmail.org/pls/otn/f..._BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,78401

> less and less likely

subjective probability estimate ?


-------------------------------------------------

I assume they just look at #differences of sequences in the 8 segments ?
Or do they also take into consideration which polymorphism
emerged in which sequences ?


compare differences in 1918ff

  1 >A/Brevig Mission/1/1918///     
  1:  0,  0,  0,  0,  0,  0,  0,  0   A/Brevig Mission/1/1918///
  2: 48, 32, 37, 74, 42, 62, 27, 29   A/Wilson-Smith/33///
  3: 50, 38, 45, 82, 49, 70, 40, 39   A/Alaska/1935///
  4: 46, 31, 36, 75, 40, 71, 25, 28   A/Melbourne/35///
  5: 45, 36, 42, 72, 44, 59, 29, 31   A/Phila/1935///
  6: 45, 34, 44, 75, 46, 60, 31, 32   A/Henry/1936///
  7: 44, 46, 52, 66, 44, 51, 41, 45   A/swine/Iowa/15/1930///
  8: 44, 46, 51, 65, 44, 51, 39, 45   A/swine/1931///
  9: 46, 47, 49, 80, 48, 51, 40, 50   A/swine/1976/1931///
 10: 55, 55, 52, 74, 56, 60, 38, 42   A/swine/Ohio/23/1935///
 11: 44, 47, 49, 64, 43, 50, 35, 44   A/swine/Jamesburg/1942///

  2 >A/Wilson-Smith/33///           
  1: 48, 32, 37, 74, 42, 62, 27, 29   A/Brevig Mission/1/1918///
  2:  0,  0,  0,  0,  0,  0,  0,  0   A/Wilson-Smith/33///
  3: 30, 23, 24, 45, 36, 37, 31, 29   A/Alaska/1935///
  4: 19, 12, 15, 35, 24, 42, 18, 21   A/Melbourne/35///
  5: 26, 18, 22, 29, 28, 28, 20, 23   A/Phila/1935///
  6: 26, 17, 25, 35, 32, 31, 20, 22   A/Henry/1936///
  7: 77, 71, 70,122, 74, 90, 51, 67   A/swine/Iowa/15/1930///
  8: 77, 71, 69,119, 73, 90, 49, 67   A/swine/1931///
  9: 78, 73, 70,148, 75, 90, 52, 72   A/swine/1976/1931///
 10: 86, 81, 73,121, 86, 96, 50, 65   A/swine/Ohio/23/1935///
 11: 76, 74, 70,116, 71, 91, 49, 66   A/swine/Jamesburg/1942///

  3 >A/Alaska/1935///               
  1: 50, 38, 45, 82, 49, 70, 40, 39   A/Brevig Mission/1/1918///
  2: 30, 23, 24, 45, 36, 37, 31, 29   A/Wilson-Smith/33///
  3:  0,  0,  0,  0,  0,  0,  0,  0   A/Alaska/1935///
  4: 29, 22, 25, 37, 36, 48, 29, 29   A/Melbourne/35///
  5: 17, 16, 13, 27, 18, 20, 27, 21   A/Phila/1935///
  6:  8,  9,  9, 20, 12, 13, 15,  9   A/Henry/1936///
  7: 81, 76, 80,127, 78, 99, 66, 73   A/swine/Iowa/15/1930///
  8: 81, 76, 79,125, 78, 99, 64, 73   A/swine/1931///
  9: 82, 79, 78,154, 79, 99, 66, 76   A/swine/1976/1931///
 10: 89, 86, 83,127, 88,103, 65, 72   A/swine/Ohio/23/1935///
 11: 81, 80, 79,122, 76,101, 64, 72   A/swine/Jamesburg/1942///

  4 >A/Melbourne/35///              
  1: 46, 31, 36, 75, 40, 71, 25, 28   A/Brevig Mission/1/1918///
  2: 19, 12, 15, 35, 24, 42, 18, 21   A/Wilson-Smith/33///
  3: 29, 22, 25, 37, 36, 48, 29, 29   A/Alaska/1935///
  4:  0,  0,  0,  0,  0,  0,  0,  0   A/Melbourne/35///
  5: 24, 17, 19, 23, 26, 35, 20, 19   A/Phila/1935///
  6: 24, 15, 24, 27, 28, 41, 18, 22   A/Henry/1936///
  7: 77, 68, 73,121, 72,101, 52, 66   A/swine/Iowa/15/1930///
  8: 77, 68, 72,118, 72,101, 50, 66   A/swine/1931///
  9: 80, 71, 72,140, 74,101, 51, 71   A/swine/1976/1931///
 10: 87, 78, 76,120, 84,106, 51, 64   A/swine/Ohio/23/1935///
 11: 78, 71, 72,115, 70,101, 48, 65   A/swine/Jamesburg/1942///

  5 >A/Phila/1935///                
  1: 45, 36, 42, 72, 44, 59, 29, 31   A/Brevig Mission/1/1918///
  2: 26, 18, 22, 29, 28, 28, 20, 23   A/Wilson-Smith/33///
  3: 17, 16, 13, 27, 18, 20, 27, 21   A/Alaska/1935///
  4: 24, 17, 19, 23, 26, 35, 20, 19   A/Melbourne/35///
  5:  0,  0,  0,  0,  0,  0,  0,  0   A/Phila/1935///
  6: 11,  9, 13, 18,  9, 12, 16, 14   A/Henry/1936///
  7: 78, 71, 78,119, 74, 92, 56, 68   A/swine/Iowa/15/1930///
  8: 78, 71, 77,117, 74, 92, 54, 68   A/swine/1931///
  9: 79, 72, 77,143, 78, 92, 55, 70   A/swine/1976/1931///
 10: 85, 80, 80,119, 84, 94, 53, 65   A/swine/Ohio/23/1935///
 11: 77, 74, 77,113, 72, 92, 52, 66   A/swine/Jamesburg/1942///

  6 >A/Henry/1936///                
  1: 45, 34, 44, 75, 46, 60, 31, 32   A/Brevig Mission/1/1918///
  2: 26, 17, 25, 35, 32, 31, 20, 22   A/Wilson-Smith/33///
  3:  8,  9,  9, 20, 12, 13, 15,  9   A/Alaska/1935///
  4: 24, 15, 24, 27, 28, 41, 18, 22   A/Melbourne/35///
  5: 11,  9, 13, 18,  9, 12, 16, 14   A/Phila/1935///
  6:  0,  0,  0,  0,  0,  0,  0,  0   A/Henry/1936///
  7: 77, 72, 80,120, 77, 91, 59, 69   A/swine/Iowa/15/1930///
  8: 77, 72, 79,118, 76, 91, 56, 69   A/swine/1931///
  9: 78, 75, 79,149, 79, 91, 57, 71   A/swine/1976/1931///
 10: 85, 83, 83,119, 86, 97, 53, 67   A/swine/Ohio/23/1935///
 11: 76, 76, 79,114, 74, 93, 54, 67   A/swine/Jamesburg/1942///

  7 >A/swine/Iowa/15/1930///        
  1: 44, 46, 52, 66, 44, 51, 41, 45   A/Brevig Mission/1/1918///
  2: 77, 71, 70,122, 74, 90, 51, 67   A/Wilson-Smith/33///
  3: 81, 76, 80,127, 78, 99, 66, 73   A/Alaska/1935///
  4: 77, 68, 73,121, 72,101, 52, 66   A/Melbourne/35///
  5: 78, 71, 78,119, 74, 92, 56, 68   A/Phila/1935///
  6: 77, 72, 80,120, 77, 91, 59, 69   A/Henry/1936///
  7:  0,  0,  0,  0,  0,  0,  0,  0   A/swine/Iowa/15/1930///
  8:  0,  0,  0,  2,  0,  0,  2,  1   A/swine/1931///
  9: 11,  7, 10, 26, 15,  0, 13, 16   A/swine/1976/1931///
 10: 24, 21, 28, 37, 34, 21, 13, 21   A/swine/Ohio/23/1935///
 11:  9,  8, 11, 15,  6,  7, 10,  8   A/swine/Jamesburg/1942///

  8 >A/swine/1931///                
  1: 44, 46, 51, 65, 44, 51, 39, 45   A/Brevig Mission/1/1918///
  2: 77, 71, 69,119, 73, 90, 49, 67   A/Wilson-Smith/33///
  3: 81, 76, 79,125, 78, 99, 64, 73   A/Alaska/1935///
  4: 77, 68, 72,118, 72,101, 50, 66   A/Melbourne/35///
  5: 78, 71, 77,117, 74, 92, 54, 68   A/Phila/1935///
  6: 77, 72, 79,118, 76, 91, 56, 69   A/Henry/1936///
  7:  0,  0,  0,  2,  0,  0,  2,  1   A/swine/Iowa/15/1930///
  8:  0,  0,  0,  0,  0,  0,  0,  0   A/swine/1931///
  9: 11,  7,  9, 23, 14,  0, 11, 16   A/swine/1976/1931///
 10: 24, 21, 27, 35, 33, 21, 11, 21   A/swine/Ohio/23/1935///
 11:  9,  8, 10, 14,  5,  7,  8,  8   A/swine/Jamesburg/1942///

  9 >A/swine/1976/1931///           
  1: 46, 47, 49, 80, 48, 51, 40, 50   A/Brevig Mission/1/1918///
  2: 78, 73, 70,148, 75, 90, 52, 72   A/Wilson-Smith/33///
  3: 82, 79, 78,154, 79, 99, 66, 76   A/Alaska/1935///
  4: 80, 71, 72,140, 74,101, 51, 71   A/Melbourne/35///
  5: 79, 72, 77,143, 78, 92, 55, 70   A/Phila/1935///
  6: 78, 75, 79,149, 79, 91, 57, 71   A/Henry/1936///
  7: 11,  7, 10, 26, 15,  0, 13, 16   A/swine/Iowa/15/1930///
  8: 11,  7,  9, 23, 14,  0, 11, 16   A/swine/1931///
  9:  0,  0,  0,  0,  0,  0,  0,  0   A/swine/1976/1931///
 10: 29, 21, 26, 43, 38, 21, 12, 28   A/swine/Ohio/23/1935///
 11:  7,  5,  7, 17, 12,  7,  7, 15   A/swine/Jamesburg/1942///

 10 >A/swine/Ohio/23/1935///        
  1: 55, 55, 52, 74, 56, 60, 38, 42   A/Brevig Mission/1/1918///
  2: 86, 81, 73,121, 86, 96, 50, 65   A/Wilson-Smith/33///
  3: 89, 86, 83,127, 88,103, 65, 72   A/Alaska/1935///
  4: 87, 78, 76,120, 84,106, 51, 64   A/Melbourne/35///
  5: 85, 80, 80,119, 84, 94, 53, 65   A/Phila/1935///
  6: 85, 83, 83,119, 86, 97, 53, 67   A/Henry/1936///
  7: 24, 21, 28, 37, 34, 21, 13, 21   A/swine/Iowa/15/1930///
  8: 24, 21, 27, 35, 33, 21, 11, 21   A/swine/1931///
  9: 29, 21, 26, 43, 38, 21, 12, 28   A/swine/1976/1931///
 10:  0,  0,  0,  0,  0,  0,  0,  0   A/swine/Ohio/23/1935///
 11: 26, 23, 27, 36, 31, 20,  9, 20   A/swine/Jamesburg/1942///

 11 >A/swine/Jamesburg/1942///      
  1: 44, 47, 49, 64, 43, 50, 35, 44   A/Brevig Mission/1/1918///
  2: 76, 74, 70,116, 71, 91, 49, 66   A/Wilson-Smith/33///
  3: 81, 80, 79,122, 76,101, 64, 72   A/Alaska/1935///
  4: 78, 71, 72,115, 70,101, 48, 65   A/Melbourne/35///
  5: 77, 74, 77,113, 72, 92, 52, 66   A/Phila/1935///
  6: 76, 76, 79,114, 74, 93, 54, 67   A/Henry/1936///
  7:  9,  8, 11, 15,  6,  7, 10,  8   A/swine/Iowa/15/1930///
  8:  9,  8, 10, 14,  5,  7,  8,  8   A/swine/1931///
  9:  7,  5,  7, 17, 12,  7,  7, 15   A/swine/1976/1931///
 10: 26, 23, 27, 36, 31, 20,  9, 20   A/swine/Ohio/23/1935///
 11:  0,  0,  0,  0,  0,  0,  0,  0   A/swine/Jamesburg/1942///

with 1972ff:

  1 >1972//,1643,RUS,A/Udorn/307/72            
  1:  0,  0,  0,  0,  0,  0,  0,  0   1972//,1643,RUS,A/Udorn/307/72
  2: 14, 17, 14, 33, 18, 20, 14, 26   1979//,4199,THA,A/Bangkok/01/79
  3: 20, 23, 19, 46, 25, 31, 21, 29   1983//,5660,HKG,A/HK/14/83
  4: 28, 38, 31, 62, 33, 46, 24, 34   1989//,7852,CHN,A/Beijing/353/89
  5: 40, 53, 42, 82, 42, 68, 30, 40   1997/11/29,10924,USA,A/NY/503/97
  6: 53, 65, 52,113, 62, 92, 42, 52   2007/02/06,14278,AUS,A/Brisbane/10/07

  2 >1979//,4199,THA,A/Bangkok/01/79           
  1: 14, 17, 14, 33, 18, 20, 14, 26   1972//,1643,RUS,A/Udorn/307/72
  2:  0,  0,  0,  0,  0,  0,  0,  0   1979//,4199,THA,A/Bangkok/01/79
  3:  7,  7,  6, 16, 12, 13,  8, 10   1983//,5660,HKG,A/HK/14/83
  4: 16, 23, 19, 34, 21, 31, 13, 15   1989//,7852,CHN,A/Beijing/353/89
  5: 30, 40, 32, 61, 32, 55, 21, 21   1997/11/29,10924,USA,A/NY/503/97
  6: 44, 53, 43, 92, 50, 80, 35, 33   2007/02/06,14278,AUS,A/Brisbane/10/07

  3 >1983//,5660,HKG,A/HK/14/83                
  1: 20, 23, 19, 46, 25, 31, 21, 29   1972//,1643,RUS,A/Udorn/307/72
  2:  7,  7,  6, 16, 12, 13,  8, 10   1979//,4199,THA,A/Bangkok/01/79
  3:  0,  0,  0,  0,  0,  0,  0,  0   1983//,5660,HKG,A/HK/14/83
  4: 10, 20, 17, 21, 10, 19,  7,  7   1989//,7852,CHN,A/Beijing/353/89
  5: 25, 35, 31, 49, 23, 44, 15, 13   1997/11/29,10924,USA,A/NY/503/97
  6: 41, 49, 47, 82, 45, 72, 29, 27   2007/02/06,14278,AUS,A/Brisbane/10/07

  4 >1989//,7852,CHN,A/Beijing/353/89          
  1: 28, 38, 31, 62, 33, 46, 24, 34   1972//,1643,RUS,A/Udorn/307/72
  2: 16, 23, 19, 34, 21, 31, 13, 15   1979//,4199,THA,A/Bangkok/01/79
  3: 10, 20, 17, 21, 10, 19,  7,  7   1983//,5660,HKG,A/HK/14/83
  4:  0,  0,  0,  0,  0,  0,  0,  0   1989//,7852,CHN,A/Beijing/353/89
  5: 18, 21, 19, 31, 16, 29,  8,  8   1997/11/29,10924,USA,A/NY/503/97
  6: 34, 37, 32, 71, 38, 59, 22, 22   2007/02/06,14278,AUS,A/Brisbane/10/07

  5 >1997/11/29,10924,USA,A/NY/503/97          
  1: 40, 53, 42, 82, 42, 68, 30, 40   1972//,1643,RUS,A/Udorn/307/72
  2: 30, 40, 32, 61, 32, 55, 21, 21   1979//,4199,THA,A/Bangkok/01/79
  3: 25, 35, 31, 49, 23, 44, 15, 13   1983//,5660,HKG,A/HK/14/83
  4: 18, 21, 19, 31, 16, 29,  8,  8   1989//,7852,CHN,A/Beijing/353/89
  5:  0,  0,  0,  0,  0,  0,  0,  0   1997/11/29,10924,USA,A/NY/503/97
  6: 20, 23, 23, 46, 26, 37, 20, 16   2007/02/06,14278,AUS,A/Brisbane/10/07

  6 >2007/02/06,14278,AUS,A/Brisbane/10/07     
  1: 53, 65, 52,113, 62, 92, 42, 52   1972//,1643,RUS,A/Udorn/307/72
  2: 44, 53, 43, 92, 50, 80, 35, 33   1979//,4199,THA,A/Bangkok/01/79
  3: 41, 49, 47, 82, 45, 72, 29, 27   1983//,5660,HKG,A/HK/14/83
  4: 34, 37, 32, 71, 38, 59, 22, 22   1989//,7852,CHN,A/Beijing/353/89
  5: 20, 23, 23, 46, 26, 37, 20, 16   1997/11/29,10924,USA,A/NY/503/97
  6:  0,  0,  0,  0,  0,  0,  0,  0   2007/02/06,14278,AUS,A/Brisbane/10/07

here we have PB1 getting more mutations than PB2.
Would the same analysis as in the paper conclude that PB1
didn't come from Udorn/72 ?

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

1 >A/Brevig Mission/1/1918///
1: 0, 0, 0, 0, 0, 0, 0, 0 A/Brevig Mission/1/1918///
2: 48, 32, 37, 74, 42, 62, 27, 29 A/Wilson-Smith/33///
3: 50, 38, 45, 82, 49, 70, 40, 39 A/Alaska/1935///
4: 46, 31, 36, 75, 40, 71, 25, 28 A/Melbourne/35///
5: 45, 36, 42, 72, 44, 59, 29, 31 A/Phila/1935///
6: 45, 34, 44, 75, 46, 60, 31, 32 A/Henry/1936///
7: 44, 46, 52, 66, 44, 51, 41, 45 A/swine/Iowa/15/1930///
8: 44, 46, 51, 65, 44, 51, 39, 45 A/swine/1931///
9: 46, 47, 49, 80, 48, 51, 40, 50 A/swine/1976/1931///
10: 55, 55, 52, 74, 56, 60, 38, 42 A/swine/Ohio/23/1935///
11: 44, 47, 49, 64, 43, 50, 35, 44 A/swine/Jamesburg/1942///

Hi gsgs

I need a little help reading this table.

Is it

PB2, PB1, PA, HA, NP, NA, M, NS - across the top

And pairwise nucleotide differences compared going down the table?

If it is, this is similar to what Gorman did (Gorman et al. Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses. Journal of Virology (1991) vol. 65 (7) pp. 3704-14). They conducted a linear regression based on accumulated nucleotide differences over time. However, they only analysed data from the NP gene. The BEAST analysis allows for a more accurate estimation of dates by not assuming a strict clock. Rather, these substitution rates are variable along a phylogeny.

Check out this paper to get an idea of how the relaxed clock models work to estimate dates.

Drummond et al. Relaxed phylogenetics and dating with confidence. Plos Biol (2006) vol. 4 (5) pp. e88

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

here we have PB1 getting more mutations than PB2.
Would the same analysis as in the paper conclude that PB1
didn't come from Udorn/72 ?

It is difficult to make this conclusion. Personally I prefer to work within a phylogenetic framework to select sequences to compare. Are these sequences related and are you sure there has not been any further reassortment? If there has been then the accumulated mutations would be artificially increased?

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

> Is it
> PB2, PB1, PA, HA, NP, NA, M, NS - across the top
> And pairwise nucleotide differences compared going down the table?

yes, nucleotide-differences in promille of available nucleotides.
Usually coding region only, order of the 8 segments as you said.
One line with the comparing strain - then several lines with the
compared strains

> The BEAST analysis allows for a more accurate estimation of dates
> by not assuming a strict clock. Rather, these substitution
>rates are variable along a phylogeny.

but does it just consider differences or does it depend at which positions
they occur ?

> Check out this paper to get an idea of how the relaxed clock models
> work to estimate dates.
> Drummond et al. Relaxed phylogenetics and dating with confidence.
> Plos Biol (2006) vol. 4 (5) pp. e88[/QUOTE]

thanks. Needs some time, presumably ... not done yet.
(Is there a good summary ?)

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

> It is difficult to make this conclusion.

more difficult than the reassortment conclusion of 1918-->1933 ?

> Personally I prefer to work within a phylogenetic framework
> to select sequences to compare.

feel free. If you need the sequences in some special format, tell me.

> Are these sequences related

my collection of representative human H3N2-genomes.
They are selected "bottle-neck-sequences", subsequent viruses
available at genbank usually descend from them without reassortment
with different previous strains.

> and are you sure there has not been any further reassortment?

never sure, but I consider it likely that there was no reassortment
with viruses prior to (and essentially different to) Udorn/1972 in
the involved viruses.

> If there has been then the accumulated mutations would be
> artificially increased ?

you would see "unusual" differences in some segments.
I have a program to search all pairs of viruses in a database
and all 28 pairs of segments for these

p-value=0.006 for reassortment-separation of PB1 and PB2
in HK/14/83 and Beijing/353/89

p-value=0.003 for reassortment-separation of PB1 and PB2
in BM18 and WS33


but as you can see, H3N2 just mutated a bit more in PB1 during the years
in all the viruses while early human H1N1 just mutated a bit more in PB2 (?)

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

>
> The BEAST analysis allows for a more accurate estimation of dates
> by not assuming a strict clock. Rather, these substitution
>rates are variable along a phylogeny.

but does it just consider differences or does it depend at which positions
they occur ?

The method developed by Drummond and others is a phylogenetic method that includes time into the estimation of the phylogeny; quite different than counting the number of differences. It is a fully parametric method Bayesian method that uses a Markov Chain-Monte Carlo method to search the tree space and assess the confidence in a particular estimate. A wide variety of evolutionary models can be applied to different datasets including models that are partitioned into codon positions to account for differences in nucleotide substitution patters at 1st, 2nd and 3rd position of the genetic code.

The method is robust and flexible. A whole team of very smart people are working out new methods and models all the time. It's not the easiest place to start if you're unfamiliar with phylogenetic analysis, but it is proven and rapidly gaining acceptance. Even now you're seeing more and more papers using BEAST to analyse sequence data. A major reason for this is that viruses are measurably evolving populations and the temporal signal is very strong, often evident in phylogenetic analyses that do not include time in the evolutionary model.


http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040088

Abstract

In phylogenetics, the unrooted model of phylogeny and the strict molecular clock model are two extremes of a continuum. Despite their dominance in phylogenetic inference, it is evident that both are biologically unrealistic and that the real evolutionary process lies between these two extremes. Fortunately, intermediate models employing relaxed molecular clocks have been described. These models open the gate to a new field of “relaxed phylogenetics.” Here we introduce a new approach to performing relaxed phylogenetic analysis. We describe how it can be used to estimate phylogenies and divergence times in the face of uncertainty in evolutionary rates and calibration times. Our approach also provides a means for measuring the clocklikeness of datasets and comparing this measure between different genes and phylogenies. We find no significant rate autocorrelation among branches in three large datasets, suggesting that autocorrelated models are not necessarily suitable for these data. In addition, we place these datasets on the continuum of clocklikeness between a strict molecular clock and the alternative unrooted extreme. Finally, we present analyses of 102 bacterial, 106 yeast, 61 plant, 99 metazoan, and 500 primate alignments. From these we conclude that our method is phylogenetically more accurate and precise than the traditional unrooted model while adding the ability to infer a timescale to evolution.

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

I'm not finding anything that indicates that data other than
mere difference-counts of virus-pairs in the segments are being
used. So, presumably just the data which I gave in the tables above.

But apparantly more sophisticated analysis of trends and timings

however, not influenza-specific

they estimated August 2008 - Jan 2009 as the likely start of ******
leading to headlines in the press that it may have been
circulating since August

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

I'm not finding anything that indicates that data other than
mere difference-counts of virus-pairs in the segments are being
used. So, presumably just the data which I gave in the tables above.

But apparantly more sophisticated analysis of trends and timings

however, not influenza-specific

they estimated August 2008 - Jan 2009 as the likely start of ******
leading to headlines in the press that it may have been
circulating since August

Quite different. Give it another read. The paper is freely available at the link I posted.

In this case rates that determine the branch lengths are drawn from a parametric distribution where the mean of which can be determined apriori or estimated from the sampled trees.

By relaxing the constraints poorly sampled data or even increased rates due to interspecies transmission events can be accounted for in the date estimates.

Since you're a math guy I think you'll appreciate the methods section in the paper. Lots of fun symbols and hyperparameters of hyperparameters, but, in my opinion, elegant.

While not influenza specific it certainly was designed with analysing fast evolving viruses in mind.

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

long paper, no good summary.
I had a brief look and still didn't find anything
to indicate they use something else than just
(nucleotide-)differences.
But then we just have the data, shown above.
However sophisticated the method, it is hard to imagine
that they can conclude more than what you can just
see or picture/graph when comparing how other strains
evolve, e.g. H3N2 or H5N1.
Test it to predict their (known) reassortments by ignoring
one decade or just some years !


Maybe a better model looks (also) at individual polymorphisms ?



it's not specific to segmented viruses which reassort and have
different rates in the segments, depending on immunity
and thus host-species. Which have codon-bias and more
A,T nucleotides in mammals.
Which preferrably reassort HA and NA, which have seasonality,..

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

most obvious reassortment events in H3N2 :

new segments,year,virus,comment

24,1968, A/HK/1/68, H2N2 acquired avian H3-HA, causing a pandemic
1245,1969, A/HK/3/69
1345,1971, A/HK/46/71
278,1972, A/Udorn/72
146,1972, A/HK/50/72
26,1993, A/NY/758/93
17,1998, A/NY/521/98
356,1999, A/NY/332/99
38,2000, A/NY/187/00,
4,2003, A/NY/213/03, Fujian strain acquired a new HA, escaping the
vaccine and causing a severe season in USA
1,2004, A/Queensland/47/04, Fujian virus acquired PB2 from
non-Fujian H3N2 but didn't spread very much

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

most obvious reassortment events in H3N2 :

new segments,year,virus,comment

4,2003, A/NY/213/03, Fujian strain acquired a new HA, escaping the
vaccine and causing a severe season in USA
1,2004, A/Queensland/47/04, Fujian virus acquired PB2 from
non-Fujian H3N2 but didn't spread very much

What did 2002 Korean isolates acquire?

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

that was just copied from this thread:
http://www.setbb.com/fluwiki2/viewtopic.php?t=339&mforum=fluwiki2

database from 2008, only complete genomes, searching for
reassortments, not recombinations