Announcement

Collapse
No announcement yet.

recombination in H5-flu-viruses

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • recombination in H5-flu-viruses

    I finished examining the H5-viruses for recombination-candidates.
    11 very clear recombinants, the candidate which has most possible
    partners gets a "*".\\\\

    Code:
    PB2:Tree sparrow/Henan/2/2004(H5N1)  *Tree sparrow/Henan/4/2004(H5N1)
    PB2:Ck/Korea/ES/03(H5N1)             *SCk/HK/YU100/2002(H5N1)
    PB2:goose/Guangxi/914/2004(H5N1)     *Dk/Guangxi/668/2004(H5N1)
    PB2:*WildDk/Guangdong/314/2004(H5N1)  Ck/Henan/13/2004(H5N1)
    PB1:Ck/Yamaguchi/7/2004(H5N1)        *Ck/Hebei/718/2001(H5N1)
    PB1:Gf/HK/38/2002(H5N1)              *Ck/HK/37.4/2002(H5N1)
    PA: Ck/HK/31.4/02(H5N1)              *Ck/HK/37.4/2002(H5N1)
    PA: *SCk/HK/YU100/2002(H5N1)          Ck/HK/31.2/2002(H5N1)
    NP: Gf/HK/38/2002(H5N1)              *Ck/HK/37.4/2002(H5N1)
    NA: Ck/Hong Kong/258/97(H5N1)        *Ck/Hebei/718/2001(H5N1)
    NA: *tree sparrow/Henan/3/2004(H5N1)  tree sparrow/Henan/4/2004(H5N1)
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

  • #2
    Re: recombination in H5-flu-viruses

    it seems that recombination prefers other genes than HA in H5-viruses.
    I didn't find any clear example of recombination in H5-HA. OK, I mean
    "this" sort of recombination, Niman would identify other sorts of
    recombination which even result in single nucleotide-changes.

    But, as the two recent papers about binding of H5N1 to human
    respiratory-tract-cells show, recombination of H5N1 might not be
    required and a series of single-nucleotide-changes could do the trick.

    I measured the "clustering" of mutations in the genes
    (this might indicate recombination):
    Code:
    PB2 223:496, 7497:15,353:620,,120:599,  979: 7, 637:1131
    PB1  75:428,  483:17,266:590,, 81:492,  385: 5, 620: 996
    PA  192:383,  820:17,340:651,, 77:484,  448: 5,1119:1387
    HA  385:526,  859:47,489:660,,156:499,  360:15,1072:1224
    NP  310:413,  584:15,260:663,,163:298,  281: 4, 876:1253
    NA  169:527,10414:24,244:673,,176:369, 2341: 2, 830:1242
    M   357:473, 2104: 5,224:755,,106,127,15054: 1, 735:1793
    NS  204:510,42870:16, 39:764,, 27:343,34789: 3, 602:1966
    the exact meaning of the numbers is hard to explain,
    but the 2nd value after ":" is always from a randomized run.
    The 2nd part after ",," considers only 3rd position mutations (in codon),
    these often don't change the properties of the virus.
    The NS gene shows high tendency for clustering the mutations but
    without showing the clear identifiable candiates for recombination as
    in the 11 examples above, so there could be other reasons for the
    clustering - the head-part could be more susceptible to mutations
    than the tail-part or vice versa.
    Maybe I should restrict to mutations which don't change an
    amino-acid ? These should occur more "randomly".
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

    Comment


    • #3
      Re: recombination in H5-flu-viruses

      here are H1 and H5 recombination candidates. First entry has most
      partners, second entry is best partner for first. (but there are probably
      many others)


      Code:
       
      H1:244,272,240,796,351,383,299,238 sequences for the 8 segments 
      PB2,PB1,PA,HA,NP,NA,M,NS examined
       
      [FONT=Arial]PB2:Swine/Illinois/100085A/01(H1N2)     Swine/Ontario/53518/03(H1N1)
      PB1:Swine/Ontario/57561/03(H1N1)        Mallard/Alberta/130/2003(H1N1)
      PA :WSN/33(H1N1)                        Swine/Italy/1513-1/98(H1N1)     
      PA :Swine/Ontario/57561/03(H1N1)        Human/Denver/57(H1N1)     
      PA :Swine/Tennessee/26/77(H1N1)         Swine/Ontario/53518/03(H1N1)
      NA :Human/USA/1995(H1N1)                Human/Slovakia/2000(H1N1)    
      HA :Swine/Japan/1992(H1N1)              Human/USA/1991(H1N1)
      NS :Swine/Korea/S10/2004(H1N1)          Swine/Korea/S175/2004(H1N1)
       
      NP :0005250  Swine/Canada/2003(H1N1)       Swine/USA/2001(H1N2)   
      NA :0016467  Swine/Canada/2003(H1N1)       Human/USA/1994(H1N1)
      PA :0406947  Swine/Alberta/56626/03(H1N1)  Swine/USA/1931(H1N1)     
      PB2:2895191  Swine/Tennessee/24/77(H1N1)   Swine/Ontario/55383/04(H1N2) 
       
      ---------------------------------------------------------------------------
       
      H5:384,382,374,734,402,594,477,518 sequences for the 8 segments examined
       
      PB2:Tree sparrow/Henan/4/2004(H5N1)  Tree sparrow/Henan/2/2004(H5N1) 
      PB2:SCk/HK/YU100/2002(H5N1)          Ck/Korea/ES/03(H5N1)            
      PB2:Dk/Guangxi/668/2004(H5N1)        goose/Guangxi/914/2004(H5N1)     
      PB2:WildDk/Guangdong/314/2004(H5N1)  Ck/Henan/13/2004(H5N1)
      PB1:Ck/Hebei/718/2001(H5N1)          Ck/Yamaguchi/7/2004(H5N1)   
      PB1:Ck/HK/37.4/2002(H5N1)            Gf/HK/38/2002(H5N1)              
      PA :Ck/HK/37.4/2002(H5N1)            Ck/HK/31.4/02(H5N1)              
      PA :SCk/HK/YU100/2002(H5N1)          Ck/HK/31.2/2002(H5N1)
      NP :Ck/HK/37.4/2002(H5N1)            Gf/HK/38/2002(H5N1)      
      NA :Ck/Hebei/718/2001(H5N1)          Ck/Hong Kong/258/97(H5N1)       
      NA :tree sparrow/Henan/3/2004(H5N1)  tree sparrow/Henan/4/2004(H5N1)
       
      PA :0256204  Ck/Hebei/108/02(H5N1)   Dk/Shanghai/35/2002(H5N1) 
       
      ----------------------------------------------------------------------
      [/FONT]
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #4
        Re: recombination in H5-flu-viruses

        I measured the clustering of mutations of the genes
        (this might indicate recombination):

        Code:
        H5:384,382,374,402,594,477,518 sequences examined
        
             l5 (p=) l5 (#)  (p=)      same 3 
        --------------------------------------------------------
        PB2 223:496, 7497:15,353:620,,120:599,  979: 7, 637:1131
        PB1  75:428,  483:17,266:590,, 81:492,  385: 5, 620: 996
        PA  192:383,  820:17,340:651,, 77:484,  448: 5,1119:1387
        HA  385:526,  859:47,489:660,,156:499,  360:15,1072:1224
        NP  310:413,  584:15,260:663,,163:298,  281: 4, 876:1253
        NA  169:527,10414:24,244:673,,176:369, 2341: 2, 830:1242
        M   357:473, 2104: 5,224:755,,106:127,15054: 1, 735:1793
        NS  204:510,42870:16, 39:764,, 27:343,34789: 3, 602:1966
        
        H1:244,272,240,796,351,383,299,238 sequences examined
        --------------------------------------------------------
        PB2 334:442,  652: 5,550:648,,294:596,   37: 4, 781: 888
        PB1  38:510,  212: 4,686:754,, 29:459,  128: 5, 855:1110
        PA   93:327, 1002: 7,268:657,,149:405,  192: 2, 642:1063
        HA  253:554,10977:62,352:720,,232:528, 1909:10,1507:1405
        NP  267:514, 3728: 4,485:781,,288:605,   33: 2, 892:1168
        NA   55:397,  974:16,527:788,,379:557,  925: 4, 922:1131
        M   259:479, 4087: 4,122:763,,391:---, 1164: 0, 621:1728
        NS  166:632, 2109: 2,322:789,, 94:---, 5135: 0,1280:1939


        The 12 numbers in
        PB2:223:496, 7497:15,353:620,,120:599, 979: 7, 637:1131
        are obtained by:

        recom pb2_h5 l5 b100 i020 (average p) recom pb2_h5 l5 b100 i020 r66 (average p)
        recom pb2_h5 l5 b100 i020 (number of pairs) recom pb2_h5 l5 b100 i020 r66 (number of pairs)
        recom pb2_h5 b100 i020 (average p) recom pb2_h5 b100 i020 r66 (average p)
        recom pb2_h5 l5 b100 i020 3 (average p) recom pb2_h5 l5 b100 i020 r66 3 (average p)
        recom pb2_h5 l5 b100 i020 3 (number of pairs) recom pb2_h5 l5 b100 i020 r66 3 (number of pairs)
        recom pb2_h5 b100 i020 3 (average p) recom pb2_h5 b100 i020 r66 3 (average p)
        I'm interested in expert panflu damage estimates
        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

        Comment


        • #5
          Re: recombination in H5-flu-viruses

          Originally posted by gsgs
          here are H1 and H5 recombination candidates. First entry has most
          partners, second entry is best partner for first. (but there are probably
          many others)


          Code:
           
          H1:244,272,240,796,351,383,299,238 sequences for the 8 segments 
          PB2,PB1,PA,HA,NP,NA,M,NS examined
           
          [FONT=Arial]PB2:Swine/Illinois/100085A/01(H1N2)     Swine/Ontario/53518/03(H1N1)
          PB1:Swine/Ontario/57561/03(H1N1)        Mallard/Alberta/130/2003(H1N1)
          PA :WSN/33(H1N1)                        Swine/Italy/1513-1/98(H1N1)     
          PA :Swine/Ontario/57561/03(H1N1)        Human/Denver/57(H1N1)     
          PA :Swine/Tennessee/26/77(H1N1)         Swine/Ontario/53518/03(H1N1)
          NA :Human/USA/1995(H1N1)                Human/Slovakia/2000(H1N1)    
          HA :Swine/Japan/1992(H1N1)              Human/USA/1991(H1N1)
          NS :Swine/Korea/S10/2004(H1N1)          Swine/Korea/S175/2004(H1N1)
           
          NP :0005250  Swine/Canada/2003(H1N1)       Swine/USA/2001(H1N2)   
          NA :0016467  Swine/Canada/2003(H1N1)       Human/USA/1994(H1N1)
          PA :0406947  Swine/Alberta/56626/03(H1N1)  Swine/USA/1931(H1N1)     
          PB2:2895191  Swine/Tennessee/24/77(H1N1)   Swine/Ontario/55383/04(H1N2) 
           
          ---------------------------------------------------------------------------
           
          H5:384,382,374,734,402,594,477,518 sequences for the 8 segments examined
           
          PB2:Tree sparrow/Henan/4/2004(H5N1)  Tree sparrow/Henan/2/2004(H5N1) 
          PB2:SCk/HK/YU100/2002(H5N1)          Ck/Korea/ES/03(H5N1)            
          PB2:Dk/Guangxi/668/2004(H5N1)        goose/Guangxi/914/2004(H5N1)     
          PB2:WildDk/Guangdong/314/2004(H5N1)  Ck/Henan/13/2004(H5N1)
          PB1:Ck/Hebei/718/2001(H5N1)          Ck/Yamaguchi/7/2004(H5N1)   
          PB1:Ck/HK/37.4/2002(H5N1)            Gf/HK/38/2002(H5N1)              
          PA :Ck/HK/37.4/2002(H5N1)            Ck/HK/31.4/02(H5N1)              
          PA :SCk/HK/YU100/2002(H5N1)          Ck/HK/31.2/2002(H5N1)
          NP :Ck/HK/37.4/2002(H5N1)            Gf/HK/38/2002(H5N1)      
          NA :Ck/Hebei/718/2001(H5N1)          Ck/Hong Kong/258/97(H5N1)       
          NA :tree sparrow/Henan/3/2004(H5N1)  tree sparrow/Henan/4/2004(H5N1)
           
          PA :0256204  Ck/Hebei/108/02(H5N1)   Dk/Shanghai/35/2002(H5N1) 
           
          ----------------------------------------------------------------------
          [/FONT]
          Yes, there are many more. In the examples above for PA you have Tennessee/26 paring up with Ontario 53518. However, it also pairs up with 5 other isoaltes from that series (11112, 55383, 23866, 48235, 57561). The location of the pairs vary from isolate to isolate, but the matches are EXACT and the EXACT match generall is for over 1000 BP for each isolate.

          Similary Tennessee/24 pairs up with 5 of these isolates in PB2 (23866, 57561, 48235, 55383, 56626). Other than 57561/56626 which pair up with each other on either side of the Tennessee homology, the sequences then are quite divergent outside of the Tennessee homology (55383 and 53518 match each other for the first 550BP and then 53518, which has no Tennesssee sequence is an exact match with the Korean sequence.

          Recombination is very clear in all 7 isolates in both of these genes (and there are more examples for the other 6 gene segments).

          Comment


          • #6
            Re: recombination in H5-flu-viruses

            this is probably since I only considered recombinations
            AB+CD--> AD or CB , so that's the lower half in page 43
            of your patent-pdf.

            BTW. the other sort, as in the upper half ABC+DEF-->AEC or DBF
            can we assume
            it's from two consecutive lower half recombinations ?
            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

            Comment


            • #7
              Re: recombination in H5-flu-viruses

              Originally posted by gsgs
              this is probably since I only considered recombinations
              AB+CD--> AD or CB , so that's the lower half in page 43
              of your patent-pdf.

              BTW. the other sort, as in the upper half ABC+DEF-->AEC or DBF
              can we assume
              it's from two consecutive lower half recombinations ?
              In some instances the second parent is not known. Thus, when two sequences are exact matchs for 1/3 of the gene and then suddenl;y diverge, one or both are recombinants, even if the divergent sequence(s) are not in the database. This can be easily seen in the swine sequences, because most of then are paired. Thus, they exactly match each other in several genes and then suddenly diverge in different directions in the paired genes.

              Comment


              • #8
                Re: recombination in H5-flu-viruses

                I'll try this ABC+DEF-->AEC thing too, but it's much slower.

                In the above lists, each isolate only occurs once and then with
                the best possible partner. The other pairings with one of the
                already used partners are omitted - else the list would be too long.

                I should also replace the "3" option by considering only A-G,C-T
                transformations in the 3rd places. These don't change the amino acid
                and thus not the properties of the virus.

                I would have expected that these mutations were completely random
                then, but I found some papers indicating that they probably aren't,
                not sure. The statistics of this sort of mutations might be useful
                to estimate the frequency of recombinations vs. random
                point-mutations.
                I'm interested in expert panflu damage estimates
                my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                Comment


                • #9
                  Re: recombination in H5-flu-viruses

                  many new H5N1-sequences had been published since that analysis in March, so here is an update with the actual H5N1-sequences from genbank. My best candidates for recombination are:

                  [the smaller the first number, the more likely it's indeed recombination]



                  see http://magictour.free.fr/reco.l8
                  for pictures of the sequence-differences



                  Code:
                  [FONT=Fixedsys]pb2
                  0000000000000  151 SCk/HK/YU100/2002            86 CK/Nakorn-Patom/THA/CU-K2/04
                  0000000000000  205 WildDk/Guangdong/314/2004   518 CK/Jilin/hg/2002
                  0000000000000  265 Dk/Guangxi/668/2004         266 Gs/Guangxi/914/2004
                  0000000000000  511 CK/Henan/wu/2004            512 CK/Hubei/wj/1997
                  0000000000000  704 CK/Guiyang/1655/2006        583 Dk/Guiyang/2231/2005  
                  0000000000000  695 Dk/Guiyang/1588/2006        697 Dk/Guiyang/1722/2006
                  0000000000001  532 mallard/Guangxi/wt/2004     521 CK/Jilin/ha/2003  
                  0000000000033  238 Tree sparrow/Henan/4/2004   236 Tree sparrow/Henan/2/2004 
                  0001489804835  519 CK/Jilin/hj/2003            441 dog/THA-Suphanburi/KU-08/04 
                  0003222184991  506 CK/Hubei/wi/1997            237 Tree sparrow/Henan/3/2004 
                  0003380760408  523 CK/Jilin/hf/2002            517 CK/Jilin/he/2002  
                  0004758580771  503 CK/Hubei/wf/2002            329 CK/THA/Nontaburi/CK-162/05 
                  0007612835529  558 CK/Jilin/hl/2004            190 CK/Korea/ES/03 
                   
                  pb1
                  0000000000000  331 CK/Hebei/718/2001        55 Ck/HongKong/YU822.2/01 
                  0000000000013  528 swine/Guangxi/wz/2004   561 CK/Jilin/hn/2003
                  0000000001586  519 CK/Jilin/xw/2003        186 Dk/Hong Kong/821/02 
                  0000000003119  149 Ck/HK/37.4/2002         147 Gf/HK/38/2002 
                  0000003360058  513 CK/Jilin/hg/2002        562 Dk/Hubei/wq/2003
                  0000004613246  564 CK/Jilin/xv/2002        428 Vietnam/CL01/2004  
                  0000005730406  512 CK/Jilin/he/2002         80 Goose/Hong Kong/ww100/01 
                  0000349988645  525 Gs/Guangdong/xb/2001    330 CK/Hebei/108/02
                  0002070938847  563 CK/Jilin/hp/2003        530 cygnus cygnus/Iran/754/2006 
                  0030102891771  507 CK/Henan/wu/2004        511 CK/Hunan/fg/2004
                  0103143415485  502 CK/Hubei/wf/2002        118 Ck/HK/409.1/02   
                  0160346378962  176 CK/Jilin/9/2004         510 CK/Jiangsu/cz1/2002
                  0322974187812  518 CK/Jilin/hd/2002        524 Gs/Fujian/bb/2003
                  0336153924881  201 WildDk/Guangdong/314/04 556 cygnus olor/Italy/742/2006
                  0355783065525  517 CK/Jilin/ha/2003        332 CK/Hebei/326/2005   
                   
                  pa
                  0000000000000  150 Ck/HK/37.4/2002              94 Dk/Guangdong/22/2002 
                  0000000000000  517 CK/Jilin/hg/2002            125 Ck/Indonesia/2A/2003 
                  0000000000000  151 SCk/HK/YU100/2002           149 Ck/HK/31.2/2002 
                  0000000035927  513 CK/Hubei/wm/1997            179 swine/Shandong/2/03  
                  0000000066064  321 CK/Hebei/108/02             103 Dk/Shanghai/35/2002
                  0000000196838  522 CK/Jilin/xw/2003             87 Dk/Fujian/01/2002  
                  0000000874887  516 CK/Jilin/he/2002            514 CK/Jiangsu/cz1/2002  
                  0000013650073  222 Dk/Fujian/1734/05           569 Ck/Thailand/NP-172/06
                  0000018479557  512 CK/Hubei/wl/1997            180 swine/Fujian/1/2003  
                  0000045022087  520 CK/Jilin/ha/2003            177 CK/Jilin/9/2004 
                  0000128813714  524 Dk/Hubei/wp/2003            563 Dk/Hubei/wq/2003
                  0000161592619  526 Dk/Zhejiang/bj/2002          44 Dk/Hong Kong/2986.1/2000
                  0000187384186  504 CK/Hubei/wi/1997            515 CK/Hunan/fg/2004
                  0000530602832  426 CK/Vietnam/134/2004         242 Dk/Viet Nam/TV-V2/2004 
                  0061751925411  518 CK/Jilin/hj/2003            191 egret/Hong Kong/757.2/03  
                  0088737223542  565 CK/Jilin/xv/2002            193 Dk/Korea/ESD1/03 
                   
                  ha
                  0000584340341  764 Dk/Zhejiang/bj/2002         743 Dk/Hubei/wg/2002  
                  0892659101122  512 Dk/Vietnam/8/05              26 Hong Kong/532/97  
                   
                  np
                  0000000000000  170 Ck/HK/37.4/2002      106 Ck/HK/31.4/02  
                  0000000612300  449 Dk/Guangxi/13/2004   584 CK/Jilin/he/2002
                  0004165278925  570 CK/Hubei/wl/1997     307 Tree sparrow/Henan/3/2004 
                  0005657958799  578 CK/Henan/wu/2004     249 Indonesia/CDC582/2006 
                  0440168002743  589 CK/Jilin/hl/2004     114 Dk/Fujian/01/2002 
                  0974755968792  591 CK/Jilin/hn/2003     344 Viet Nam/HG-178/2004  
                   
                  na
                  0000000000000  711 CK/Jilin/xw/2003          99 CK/Vietnam/CM/2004  
                  0000000051534  262 tree sparrow/Henan/4/04  762 swine/Anhui/ca/2004
                  0000092268723  508 CK/Hebei/718/2001         47 Gs/Hong Kong/3014.8/2000  
                  0000546945844  703 CK/Jiangsu/cz1/2002      707 CK/Hubei/wo/2003
                  0089600166367   63 Ck/HongKong/YU562/01     710 CK/Jilin/hf/2002
                  0920683591659  691 Dk/Hubei/wg/2002         717 goose/Guangdong/xb/2001
                   
                  m
                  0001055937111  549 Dk/Minnesota/1525/1981   203 swan/Guangxi/307/2004   
                  0002468596632  575 CK/Jilin/hf/2002         566 CK/Jiangsu/cz1/2002  
                  0004583784749  568 CK/Jilin/he/2002         492 human/Zhejiang/16/2006   
                   
                  ns
                  0000021543505  618 CK/Jilin/hg/2002        211 swine/Fujian/F1/2001 
                  0948505644666  286 Dk/Minnesota/1525/1981  205 swine/Shandong/2/03 
                  [/FONT]
                  Last edited by gsgs; November 7, 2006, 10:40 AM.
                  I'm interested in expert panflu damage estimates
                  my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                  Comment

                  Working...
                  X