DIMACS Working Group on Phylogenetic Trees and Rapidly Evolving Pathogens II
Second Working Group Meeting: June 23, 2006
DIMACS Center, CoRE Building, Rutgers University
Presented under the auspices of the Special Focus on
Computational and Mathematical Epidemiology.
- Allen Rodrigo, University of Auckland, email@example.com
- Mike Steel, University of Canterbury, M.Steel@math.canterbury.ac.nz
DIMACS Tutorial on Phylogenetic Trees and Rapidly Evolving Pathogens, June 19 - 20, 2006.
DIMACS Workshop on Phylogenetic Trees and Rapidly Evolving Diseases, June 21 - 22, 2006.
DIMACS First Working Group on Phylogenetic Trees and Rapidly Evolving Diseases I, September 7 - 8, 2004.
This working group will build on phylogenetic methods developed by
computational biologists to explore ways in which such methods can be
applied and developed to shed new light on the origin, evolution, and
likely future development of viruses and other pathogens. Phylogeny is
now a central tool for studies into the origin and diversity of
viruses such as HIV (see, e.g.,
[Pybus, Rambaut and Harvey (2000),
Rambaut, Robertson, Pybus, Peeters and Holmes (2001),]) and dengue fever virus
[Rambaut (2000)]. These and other investigations have provided new insights, such
as identifying the possible pattern of transfer of HIV-type viruses
between primate species. Phylogenetic techniques have also proved
useful in mapping the evolution of different strains of the human
influenza A virus
[Bush, Bender, Subbarao, Cox and Fitch (1999a),
Bush, Fitch, Bender and Cox (1999b)], with the goal of predicting which strain is
most likely to cause future epidemics, with applications to vaccine
development. Many of the phylogenetic techniques in use were
originally developed to investigate more traditional and well-behaved
evolutionary problems, where historical relationships are typically
represented by a binary tree with a small number of species appearing
as the leaves (tip vertices). In epidemiology the picture is more
complex and this observation underlies the task of this working
group. Even if there is a single underlying tree, it may typically
have thousands of vertices, and many of these may be of high
degree. Furthermore, data may be available not just for the species at
the leaves of the tree, but for species distributed at vertices
throughout the tree, particularly when the evolution of a virus is
studied by serial sampling in patients. This is true for retroviruses
which have a very high substitution rate, and whose molecular
evolution may be up to 106 times more rapid than eukaryotic or
[Drummond and Rodrigo (2000),
Rodrigo, Shpaer, Delwart, Iversen, Gallo, Jurgen Brojatsch, Hirsch, Walker and Mullins (1999),
Shankarappa, Margolick, Gange, Rodrigo, Upchurch, Farzadegan, Gupta, Rinaldo, Learn, He, Huang and Mullins (1999)].
New methods for dealing with these
complications will be investigated. To complicate the picture further,
it may well be more appropriate to represent the evolution of a virus
by a collection of trees, or by a digraph (or network) to recognize
the "quasispecies" nature of viruses, such as in the application of
split decomposition by Dopazo, Dress, and von Haeseler [Dopazo, Dress and von Haeseler (1993)]; we shall
pursue this direction of research. Relating population genetics
considerations (currently handled by the "coalescent" model) to
phylogeny considerations is also potentially useful [Rodrigo and Felsenstein (1999)]. However,
even here, theory has yet to be developed. For instance, the fact that
retroviral evolution occurs within a host means that viral sequences
sampled from different hosts must take account of the different
dynamics of between-host transmission histories and within-host viral
genealogies [Rodrigo (1999)]. This has consequences for the inference of
epidemiological parameters based on viral sequences obtained from
several hosts, and we will investigate them. Finally, if one wishes to
test particular epidemiological hypotheses it would be helpful to have
techniques that avoid having to fix attention on one particular
tree. This suggests devising fast methods that would average the
quantities of interest over all likely trees, weighted by how well
they describe the data - a challenge for modern computational tools
and our working group.
This meeting is by invitation only. If you are interested in participating, please contact the
Bush, R.M., Bender, C.A., Subbarao, K. Cox, N.J., and Fitch, W.M. (1999a),
"Predicting the evolution of human influenza A,"
Science, 286, 1921-1925.
Bush, R.M., Fitch, W.M., Bender, C.A., and Cox, N.J. (1999b),
"Positive selection on the H3 Hemagglutinin gene of human influenza virus A,"
Mol. Biol. Evol., 16, 1457-1465.
Dopazo, J., Dress, A., and von Haeseler, A. (1993),
"Split decomposition: A technique to analyse viral evolution,"
Proc. Natl. Acad. Sci. USA, 90, 10320-10324.
Drummond, A., and Rodrigo, A.G. (2000),
"Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA (sUPGMA),"
Molecular Biology and Evolution, 17, 1807-1815.
Pybus, O. Rambaut, A., and Harvey, P.H. (2000),
"An integrated framework for the inference of viral population history from reconstructed genealogies,"
Genetics, 155, 1429-1437.
Rambaut, A. (2000),
"Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies,"
Bioinformatics, 16, 395-399.
Rambaut, A., Robertson, D.L., Pybus, O.G., Peeters, M., and Holmes, E. (2001),
"Phylogeny and the origin of HIV-1,"
Nature, 410, 1047-1048.
Rodrigo, A.G. (1999), "HIV evolutionary genetics [Commentary],"
Proceedings of the National Academy of Sciences, 96, 10559-10561.
Rodrigo, A.G., and Felsenstein, J. (1999),
"Coalescent approaches to HIV-1 Population Genetics," in K.A. Crandall (ed.),
Molecular Evolution of HIV, Johns Hopkins University Press.
Rodrigo, A.G., Shpaer, E.G., Delwart, E.L., Iversen, A.K.N., Gallo, M.V., Jurgen Brojatsch, J., Hirsch, M.S., Walker, B.D., and Mullins, J.I. (1999),
"Coalescent estimates of HIV-1 generation time in vivo,"
Proceedings of the National Academy of Science, 96, 2187-2191.
Shankarappa, R., Margolick, R.B., Gange, S.J., Rodrigo, A.G., Upchurch, D., Farzadegan, H., Gupta, P., Rinaldo, C.R., Learn, G.H., He, X., Huang, X-L., and Mullins, J.I. (1999),
"Consistent viral evolutionary changes associated with progression of HIV-1 infection,"
Journal of Virology, 73, 10489-10502.
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Document last modified on December 14, 2005.