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Origin of outbreak (HA gene) 3 May 2009 - Oliver Pybus

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Origin of outbreak, HA gene analysis

Oliver Pybus 3-MAY-2009

This is an update of my earlier analyses of HA gene sequences from the outbreak. 

I included all available sequences ~1000nt or greater in length. The Toronto sequences were omitted as they are only ~500nt long. The complete alignment comprised 144 sequences, 1701nt in length. Many non-outbreak-related reference sequences were omitted to speed up calculation. 

Data was analysed in BEAST under a relaxed clock model (lognormal distribution). Other model used were a GTR+gamma substitution model and 10-step Bayesian skyline plot. I ran 6 independent MCMCs, totalling 60 million states.

The mean evolutionary rate was 0.00356 subs/site/year (95% HPDs: 0.00326 to 0.00388). 
The relaxed clock coefficient of variation was 0.487 (95% HPDs: 0.373 to 0.597).
The relaxed clock covariance was 0.009 (-0.12 to 0.098).

The estimated date of the common ancestor of the outbreak was mid-September 2008 - the same as in previous analyses. There is certainly enough among-branch rate variation to warrant the use of a relaxed clock, but the choice of clock model has no noticeable effects on the results.
    Download file "HAsatmcc.pdf"

    HAsatmcc.jpg
    The figure below shows the posterior probability support for nodes within the outbreak clade. Despite the small sample size, sequences from Mexico do (qualitatively) appear to be more phylogenetically dispersed than those from other locations. 

    Note to the tinfoil hat brigade: no, the virus didn't come from Kansas. The phylogenetic position of that strain has no statistical support. Only those clusters with numbers above them have any meaningful interpretation.
    Untitled-1.jpg


    Comments

    Andrew Rambaut
    May 3, 2009

    I get an older TMRCA if I assume a constant population size. With a BSP over the entire tree, that is essentially what you are doing. It is possible to set it up with the outbreak clade with a different coalescent prior. You can use <include> and <exclude> tag pairs to include and exclude taxa from a coalescent likelihood.

    Oliver Pybus
    May 3, 2009

    I understand the effect on TMRCA of using a constant size prior - but I don't think that's the same as using the BSP. There are coalescent events within the outbreak clade, hence the BSP changes quickly near the present to fit that. The BSP 'behaves' like a constant size prior when there are no coalescent events, e.g. during long terminal branches.

    Andrew Rambaut
    May 4, 2009

    I agree that in your case, the outbreak fully coalesces before you have a non-outbreak sample so you are kind of unlinking the two. However, I still think it would be better to have 1 outbreak case in your tree and then have a independent tree which shares all the substitution parameters (including rate) but has an exponential growth model on it.

    /groups/influenza/search/index.rss?sort=modifiedDate&sortDirection=reverse&tag=sectionlist/groups/influenza/search/?sort=modifiedDate&sortDirection=reverse&tag=sectionSectionsCustomTagSidebarCustomTagSidebar?sort=modifiedDate&sortDirection=reverse&tag=section0/groups/influenza/sidebar/CustomTagSidebarmodifiedDate5CustomTagSidebarreversesectionSectionscustom/groups/influenza/search/index.rss?tag=hotlist/groups/influenza/search/?tag=hotWhat’s HotHotListHot!?tag=hot20/groups/influenza/sidebar/HotListrambaut2009-07-08 14:53:06+00:002009-07-08 14:53:06updated10Updated links to final versionlycett2009-07-01 05:34:14+00:002009-07-01 05:34:14updated9rambaut2009-06-12 07:40:19+00:002009-06-12 07:40:19updated8Added tag - hotrambaut2009-06-12 07:40:17+00:002009-06-12 07:40:17addTag7rambaut2009-06-12 07:40:08+00:002009-06-12 07:40:08updated6rambaut2009-06-12 07:27:06+00:002009-06-12 07:27:06updated5rambaut2009-06-12 07:17:50+00:002009-06-12 07:17:50updated4rambaut2009-06-12 07:15:25+00:002009-06-12 07:15:25updated3rambaut2009-06-12 07:15:17+00:002009-06-12 07:15:17updated2First additionrambaut2009-06-12 07:13:50+00:002009-06-12 07:13:50created1wiki2009-07-08T14:53:06+00:00groups/influenza/wiki/1b2c3FalseH1N1: Origins and evolution of the current epidemic/groups/influenza/wiki/1b2c3/H1N1_Origins_and_evolution_of_the_current_epidemic.htmlAndrew Rambaut10 updatesH1N1: Origins and evolution of the current epidemic Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic Gavin J. D. Smith1, Dhanasekaran Vijaykris...Falserambaut2009-07-08T14:53:06+00:00Shanghai/71T/09 does not have PB2-627Klycett2009-06-28 16:11:04+00:002009-06-28 16:11:04updated7lycett2009-06-28 16:06:53+00:002009-06-28 16:06:53updated6lycett2009-06-19 07:03:23+00:002009-06-19 07:03:23updated5Added tag - hotlycett2009-06-19 07:03:22+00:002009-06-19 07:03:22addTag4A/Shanghai/71T/2009 & PB2-627Klycett2009-06-18 22:40:51+00:002009-06-18 22:40:51updated3PB2-627K on A/Shanghai/71T/2009lycett2009-06-18 22:34:10+00:002009-06-18 22:34:10updated2First additionlycett2009-06-18 22:12:59+00:002009-06-18 22:12:59created1wiki2009-06-28T16:11:04+00:00groups/influenza/wiki/8bc58FalsePB2-627K & PB2-701N in A/Shanghai/71T/2009/groups/influenza/wiki/8bc58/PB2627K__PB2701N_in_AShanghai71T2009.htmlSam Lycett7 updatesPB2-627K &amp; PB2-701N in A/Shanghai/71T/2009 Notes on A/Shanghai/71T/2009 by Sam Lycett Update 28 June 09 The sequences A/Shanghai/71T/2009 were updated on 24...Falselycett2009-06-28T16:11:04+00:00comas2009-05-10 21:28:29+00:002009-05-10 21:28:29updated6comas2009-05-10 21:27:07+00:002009-05-10 21:27:07updated5comas2009-05-10 21:26:45+00:002009-05-10 21:26:45updated4Added tag - hotcomas2009-05-10 21:26:43+00:002009-05-10 21:26:43addTag3comas2009-05-10 21:26:25+00:002009-05-10 21:26:25updated2First additioncomas2009-05-10 21:13:16+00:002009-05-10 21:13:16created1wiki2009-05-10T21:28:29+00:00groups/influenza/wiki/aba06FalseUpdated Median Joining network (HA genes) - 8 May 2009 - Iñaki Comas/groups/influenza/wiki/aba06/Updated_Median_Joining_network_HA_genes__8_May_2009__Iaki_Comas.htmlIñaki Comas6 updatesUpdated Median Joining network (HA genes) - 8 May 2009 - Iñaki Comas Here is an update of the median joining network with all swine samples available at GISAID as of 8 of May. The alignment was provided by Oliver Pyb...Falsecomas2009-05-10T21:28:29+00:00pybus2009-05-08 15:45:54+00:002009-05-08 15:45:54updated6pybus2009-05-06 19:32:17+00:002009-05-06 19:32:17updated5Added tag - selectionpybus2009-05-06 18:30:11+00:002009-05-06 18:30:11addTag4Added tag - hotpybus2009-05-06 18:29:59+00:002009-05-06 18:29:59addTag3pybus2009-05-06 18:29:25+00:002009-05-06 18:29:25updated2First additionpybus2009-05-06 18:18:26+00:002009-05-06 18:18:26created1wiki2009-05-08T15:45:54+00:00groups/influenza/wiki/87337FalseAmino acid changes in HA, NA & MP leading to outbreak 6 May 2009 - Oliver Pybus and Samir Bhatt/groups/influenza/wiki/87337/Amino_acid_changes_in_HA_NA__MP_leading_to_outbreak_6_May_2009__Oliver_Pybus_and_Samir_Bhatt.htmlOliver Pybus6 updatesAmino acid changes in HA, NA &amp; MP leading to outbreak 6 May 2009 - Oliver Pybus and Samir Bhatt So, I hear you ask, what amino acid changes have occurred along those long branches leading to the outbreak strain? Right, we've gone and ...Falsepybus2009-05-08T15:45:54+00:00comas2009-05-08 12:59:46+00:002009-05-08 12:59:46updated7rambaut2009-05-08 11:40:12+00:002009-05-08 11:40:12updated6Added tag - genetic structurecomas2009-05-08 10:49:11+00:002009-05-08 10:49:11addTag5Added tag - transmissioncomas2009-05-08 10:48:52+00:002009-05-08 10:48:52addTag4comas2009-05-08 10:45:56+00:002009-05-08 10:45:56updated3Added tag - hotcomas2009-05-08 10:44:35+00:002009-05-08 10:44:35addTag2First additioncomas2009-05-08 10:37:39+00:002009-05-08 10:37:39created1wiki2009-05-08T12:59:46+00:00groups/influenza/wiki/8e6d0FalseMedian joining network (HA gene) - 7May2009 - Iñaki Comas/groups/influenza/wiki/8e6d0/Median_joining_network_HA_gene__7May2009__Iaki_Comas.htmlIñaki Comas7 updatesMedian joining network (HA gene) - 7May2009 - Iñaki Comas I have created a median joining network with the HA sequences present in the NCBI as of 7May2009. This includes 49 isolates from different locat...Falsecomas2009-05-08T12:59:46+00:00hot/groups/influenza/search/index.rss?sort=modifiedDate&kind=all&sortDirection=reverse&excludePages=wiki/welcomelist/groups/influenza/search/?sort=modifiedDate&kind=all&sortDirection=reverse&excludePages=wiki/welcomeRecent ChangesRecentChangesListUpdates?sort=modifiedDate&kind=all&sortDirection=reverse&excludePages=wiki/welcome0/groups/influenza/sidebar/RecentChangesListmodifiedDateallRecent ChangesRecentChangesListUpdateswiki/welcomeNo recent changes.reverse5search