It's not really clear to me: Are they saying that the jump happened in a large metropolis ? Or that Kinshasa was the first large city in which HIV became an epidemic ?
The first large city.
We know the city where HIV first emerged
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Re: We know the city where HIV first emerged
#22Simian AIDS was discovered after human AIDS. How do they know the jump didn't occur in reverse? Here is the first report of simian AIDS: "Examination of the species-specific annual mortality rates of macaques at the center during the previous 4 yr showed a significant increase in deaths in 1980 and 1981" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393899/ Also, it is convenient they do not share the mcmc traces. Base…
My limited understanding is that once discovered scientists found the families of simian viruses that demonstrated evolutionary and divergence that cannot be explained in going the other way or the timeframe of human hiv. See http://news.nationalgeographic.com/news/2006/05/060525-aids-... http://www.ncbi.nlm.nih.gov/m/pubmed/8026477/# There is a video documentary that I watched in the last couple years that I was rea…
Thanks. I wonder if this analysis will be reproducible though (they don't mention any parameters...):
>"Phylogenetic analysis Phylogenetic relationships were estimated from comparisons of predicted protein sequences. Sequences were aligned using CLUSTAL (Higgins and Sharp, 1988, 1989). Evolutionary distances between all pairs of sequences were computed using Kimura's empirical method (Kimura, 1983; eqn. 4.8) to estimate the number of superimposed amino acid replacements; sites at which there was a gap in any sequence in the alignment were excluded from all comparisons. Phylogenetic relationships were estimated from these distances by the neighbor-joining method (Saitou and Nei, 1987). The reliability of branching orders was estimated by the bootstrap approach (Felsenstein, 1985). These methods were implemented using CLUSTAL V (Higgins et al., 1992).
Nucleotide accession numbers All sequences were submitted to GenBank and are available under accession numbers U03994-U04018."
It looks like those sequences are a mixture of the various proteins (env, pol, etc) so it would take some time to figure out which is which. I don't feel it like right now. It seems like getting the sequences from genbank and then aligning using default params with clustalw would be closest to their method. If someone wants to do it: http://www.ncbi.nlm.nih.gov/genbank/ http://www.genome.jp/tools/clustalw/
Re: We know the city where HIV first emerged
#23Simian AIDS was discovered after human AIDS. How do they know the jump didn't occur in reverse? Here is the first report of simian AIDS: "Examination of the species-specific annual mortality rates of macaques at the center during the previous 4 yr showed a significant increase in deaths in 1980 and 1981" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393899/ Also, it is convenient they do not share the mcmc traces. Base…
Wikipedia links to an article stating that SIV has been present in monkeys and apes for at least 32000 years: http://www.nytimes.com/2010/09/17/health/17aids.html?_r=2&sr...
They get that date by assuming humans didn't bring it to the island though, they don't do anything to rule that out:
>"Barring the possibility that humans introduced multiple species-specific SIV lineages to the wild monkey populations of Bioko, the mainland and island SIVdrl variants must have been evolving independently since Bioko became isolated ~10,000 yr B.P., and perhaps longer given the high levels of genetic diversity seen within local SIV populations."
http://www.sciencemag.org/cgi/content/abstract/329/5998/1487
Interesting stuff. I hadn't thought of this until now, but from these few papers I don't think anyone has tried very hard to rule out the human to simian transmission idea.
Re: We know the city where HIV first emerged
#24Simian AIDS was discovered after human AIDS. How do they know the jump didn't occur in reverse? Here is the first report of simian AIDS: "Examination of the species-specific annual mortality rates of macaques at the center during the previous 4 yr showed a significant increase in deaths in 1980 and 1981" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393899/ Also, it is convenient they do not share the mcmc traces. Base…
These seem to be fairly standard phylogeographic methods that are applied to a mostly uncontroversial dataset. It's basically ancestral state reconstruction where geography are the traits being reconstructed: https://en.wikipedia.org/wiki/Ancestral_reconstruction#Trait... . Although there are concerns with inferring ancestral state using these sorts of methods, the fact that the authors had some historical data means that the inferred ancestral region is far more accurate than would be possible with extant data alone.
Several of the authors are also pretty hardcore Bayesian methods people in the field of phylogenetics specifically applied to the evolution of diseases. It's unlikely that their long MCMCs were due to some kind of coverup; it's possible that either the large number of sequences made convergence more difficult and / or they wanted to be absolutely certain of their results by running their analyses longer than usual. These sorts of phylogeographic methods (especially with an asymmetric movement model and lots of different localities) tend to have likelihood surfaces with many ridges, making MCMC quite difficult for all but the most trivial datasets.
Re: We know the city where HIV first emerged
#25Belgian control of the Congo was rife with pretty extreme abuse -- the obvious, often horrifying consequences of conquest. But the influx of ambitious businesspeople and capital which they claim started the wider outbreak of HIV, is a curious case. Often people will hand-wring about vague cultural factors, but this seems like one of the most concrete major international disasters caused by rapid gentrification and in…
I think that any comparison with the Belgian rape of the Congo in the 1900's with rapid gentrification and international investment is completely unwarranted.
Re: We know the city where HIV first emerged
#26Simian AIDS was discovered after human AIDS. How do they know the jump didn't occur in reverse? Here is the first report of simian AIDS: "Examination of the species-specific annual mortality rates of macaques at the center during the previous 4 yr showed a significant increase in deaths in 1980 and 1981" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393899/ Also, it is convenient they do not share the mcmc traces. Base…
These seem to be fairly standard phylogeographic methods that are applied to a mostly uncontroversial dataset. It's basically ancestral state reconstruction where geography are the traits being reconstructed: https://en.wikipedia.org/wiki/Ancestral_reconstruction#Trait... . Although there are concerns with inferring ancestral state using these sorts of methods, the fact that the authors had some historical data means…
>"making MCMC quite difficult"
They thinned 250 million steps to 500, then it sounds like they dropped the first 50-100 on top of that post-hoc (the 10-30% burn in gives an impression of manual tinkering).
Obviously this is going to bring up questions regarding convergence, so reviewers should have asked for the diagnostic charts. This would probably have been better suited to ABC:
https://en.wikipedia.org/wiki/Approximate_Bayesian_computati...
Re: We know the city where HIV first emerged
#27Earlier quoted context omitted.
These seem to be fairly standard phylogeographic methods that are applied to a mostly uncontroversial dataset. It's basically ancestral state reconstruction where geography are the traits being reconstructed: https://en.wikipedia.org/wiki/Ancestral_reconstruction#Trait... . Although there are concerns with inferring ancestral state using these sorts of methods, the fact that the authors had some historical data means…
>"making MCMC quite difficult" They thinned 250 million steps to 500, then it sounds like they dropped the first 50-100 on top of that post-hoc (the 10-30% burn in gives an impression of manual tinkering). Obviously this is going to bring up questions regarding convergence, so reviewers should have asked for the diagnostic charts. This would probably have been better suited to ABC: https://en.wikipedia.org/wiki/Appro…
BEAST (which I assumed they used) is not very fast. 250 million generations on BEAST with the number of parameters they estimated and the size of their dataset would likely take about 2-4 weeks to run. Assuming they ran all 3 chains in parallel this is still a really long time to wait for an analysis. (edit: just checked, looks like they used 700+ sequences, so this is closer to 1-3 months of compute time)
The standard number of samples for phylogenetic analyses is 1,000-10,000 samples, trending towards the smaller as the phylogenies get larger. Since they did 3 independent analyses and combined their samples, as long as they assessed convergence and ensured that all 3 chains were converged this is likely fine. Excluding burnin is also quite typical since the MCMC move operators for phylogenetics are not very good due to the high dimensionality of the search space. ABC is also challenging to work with due to the high dimensionality (though I admit I haven't worked much with these methods in phylogenetics)
Typically in this field it is not enough to say "you didn't run your MCMC chains for long enough" or anything like that. Of course the chains should be run for longer -- theoretically speaking they should be run for infinite amount of time, but there are routine disagreements over whether 100 or 1000 effective samples are sufficient for phylogenetics. But unless there is a serious model inadequacy that the authors haven't addressed there's typically no reason to nitpick about these sorts of things. The authors have covered a lot of their bases by trying a number of different models and priors and I don't see any reason to doubt this particular study based on that.
Re: We know the city where HIV first emerged
#28Belgian control of the Congo was rife with pretty extreme abuse -- the obvious, often horrifying consequences of conquest. But the influx of ambitious businesspeople and capital which they claim started the wider outbreak of HIV, is a curious case. Often people will hand-wring about vague cultural factors, but this seems like one of the most concrete major international disasters caused by rapid gentrification and in…
_rapid gentrification_ of Congo
whuhh???
Just 'caus it had a CIA sponsored coup, doesn't mean things got any better.
Re: We know the city where HIV first emerged
#29tl;dr - Kinshasa.
Re: We know the city where HIV first emerged
#30Earlier quoted context omitted.
Wikipedia links to an article stating that SIV has been present in monkeys and apes for at least 32000 years: http://www.nytimes.com/2010/09/17/health/17aids.html?_r=2&sr...
They get that date by assuming humans didn't bring it to the island though, they don't do anything to rule that out: >"Barring the possibility that humans introduced multiple species-specific SIV lineages to the wild monkey populations of Bioko, the mainland and island SIVdrl variants must have been evolving independently since Bioko became isolated ~10,000 yr B.P., and perhaps longer given the high levels of genetic…
On the other hand SIV isn't killing the monkeys or apes it infected, which makes likely a long coevolution.