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Estimating epidemiological and evolutionary parameters from viral sequence data using phylogenetic methods

Applicant Stadler Tanja
Number 136820
Funding scheme Ambizione
Research institution Gruppe Theoretische Biologie Departement Umweltsystemwissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Infectious Diseases
Start/End 01.01.2012 - 31.12.2014
Approved amount 407'909.00
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All Disciplines (3)

Discipline
Infectious Diseases
Mathematics
Genetics

Keywords (5)

Epidemiology; Evolution; Bayesian methods; Inference; HIV

Lay Summary (English)

Lead
Lay summary

RNA viruses are characterized by short generation time and high mutation rates. Therefore even over relatively short time spans epidemiological processes leave a fingerprint in the genetic structure of viral sequences sampled from the host population. As a consequence, both epidemiological and evolutionary processes can be inferred from virus sequences. However, until now epidemiological virus sequence data have been analyzed without assuming explicit epidemiological models, and therefore the quantification of key epidemiological parameters was not possible.

The objective of this research proposal is to merge epidemiological and evolutionary models, so that both epidemiological and evolutionary parameters can be estimated on the basis of viral sequence data. The methodology will become available as part of the widely used Beast and Paml software packages.

I will use the novel methodology for three applications:

I will first investigate which treatment and intervention strategies had a significant impact on the epidemic spread of HIV in the past. The results will have the potential to support the efforts in designing improved intervention strategies in the future for HIV.

Second, I will address a key empirical paradox challenging our understanding of HIV evolutionary biology, namely the apparent incompatibility between the observed fast evolutionary rates obtained from within-host data and slow evolutionary rates obtained from between-host data.

Third, the methodology will be applied to a variety of viral epidemics in order to recover the specific epidemiological dynamics. I plan to study Influenza virus, Dengue virus, Hepatitis C virus and Rhinovirus, viruses for which enough data is available to do phylogenetic analyses.


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Bayesian inference of sampled ancestor trees for epidemiology and fossil calibration
Gavryushkina Alexandra, Welch David, Stadler Tanja, Drummond Alexei J. (2014), Bayesian inference of sampled ancestor trees for epidemiology and fossil calibration, in PLoS computational biology, 10(12), 1003919-1003919.
Epiphytic leafy liverworts diversified in angiosperm-dominated forests
Feldberg Kathrin, Schneider Harald, Stadler Tanja, Schaefer-Verwimp Alfons, Schmidt Alexander R., Heinrichs Jochen (2014), Epiphytic leafy liverworts diversified in angiosperm-dominated forests, in Scientific Reports, 4, 1.
Exact vs. approximate computation: Reconciling different estimates of Mycobacterium tuberculosis epidemiological parameters
Aandahl R. Zachariah, Stadler Tanja, Sisson Scott A., Tanaka Mark M. (2014), Exact vs. approximate computation: Reconciling different estimates of Mycobacterium tuberculosis epidemiological parameters, in GENETICS, 196(4), 1227-1230.
FOSSILS AND A LARGE MOLECULAR PHYLOGENY SHOW THAT THE EVOLUTION OF SPECIES RICHNESS, GENERIC DIVERSITY, AND TURNOVER RATES ARE DISCONNECTED
Xing Yaowu, Onstein Renske E., Carter Richard J., Stadler Tanja, Linder H. Peter (2014), FOSSILS AND A LARGE MOLECULAR PHYLOGENY SHOW THAT THE EVOLUTION OF SPECIES RICHNESS, GENERIC DIVERSITY, AND TURNOVER RATES ARE DISCONNECTED, in Evolution, 68(10), 2821-2832.
Inference of Epidemiological Dynamics Based on Simulated Phylogenies Using Birth-Death and Coalescent Models
Boskova Veronika, Bonhoeffer Sebastian, Stadler Tanja (2014), Inference of Epidemiological Dynamics Based on Simulated Phylogenies Using Birth-Death and Coalescent Models, in Plos Computational Biology, 10(11), 1.
Insights into the Early Epidemic Spread of Ebola in Sierra Leone Provided by Viral Sequence Data
Stadler Tanja, Kuhnert Denise, Rasmussen David, DuPlessis Louis (2014), Insights into the Early Epidemic Spread of Ebola in Sierra Leone Provided by Viral Sequence Data, in PLoS Currents: Outbreaks, 1(1), 1.
On Age and Species Richness of Higher Taxa
Stadler Tanja, Rabosky Daniel L., Ricklefs Robert E., Bokma Folmer (2014), On Age and Species Richness of Higher Taxa, in American Naturalist, 184(4), 447-455.
Phylogenetic analysis accounting for age-dependent death and sampling with applications to epidemics
Lambert Amaury, Alexander Helen K., Stadler Tanja (2014), Phylogenetic analysis accounting for age-dependent death and sampling with applications to epidemics, in JOURNAL OF THEORETICAL BIOLOGY, 352, 60-70.
Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth-death SIR model
Kuehnert Denise, Stadler Tanja, Vaughan Timothy G., Drummond Alexei J. (2014), Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth-death SIR model, in JOURNAL OF THE ROYAL SOCIETY INTERFACE, 11(94), 1.
Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland
Avila Dorita, Keiser Olivia, Egger Matthias, Kouyos Roger, Boeni Juerg, Yerly Sabine, Klimkait Thomas, Vernazza Pietro L., Aubert Vincent, Rauch Andri, Bonhoeffer Sebastian, Guenthard Huldrych F., Stadler Tanja, Spycher Ben D. (2014), Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland, in AMERICAN JOURNAL OF EPIDEMIOLOGY, 179(12), 1514-1525.
The fossilized birth-death process for coherent calibration of divergence-time estimates
Heath Tracy A., Huelsenbeck John P., Stadler Tanja (2014), The fossilized birth-death process for coherent calibration of divergence-time estimates, in Proceedings of the National Academy of Sciences of the United States of America, 111(29), 2957-2966.
Using an Epidemiological Model for Phylogenetic Inference Reveals Density Dependence in HIV Transmission
Leventhal Gabriel E., Guenthard Huldrych F., Bonhoeffer Sebastian, Stadler Tanja (2014), Using an Epidemiological Model for Phylogenetic Inference Reveals Density Dependence in HIV Transmission, in MOLECULAR BIOLOGY AND EVOLUTION, 31(1), 6-17.
Birth-death models and coalescent point processes: The shape and probability of reconstructed phylogenies
Lambert Amaury, Stadler Tanja (2013), Birth-death models and coalescent point processes: The shape and probability of reconstructed phylogenies, in THEORETICAL POPULATION BIOLOGY, 90, 113-128.
Birth-death skyline plot reveals temporal changes of epidemic spread in HIV and hepatitis C virus (HCV)
Stadler Tanja, Kuehnert Denise, Bonhoeffer Sebastian, Drummond Alexei J. (2013), Birth-death skyline plot reveals temporal changes of epidemic spread in HIV and hepatitis C virus (HCV), in PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(1), 228-233.
Dating Phylogenies with Sequentially Sampled Tips
Stadler Tanja, Yang Ziheng (2013), Dating Phylogenies with Sequentially Sampled Tips, in SYSTEMATIC BIOLOGY, 62(5), 674-688.
Estimating Speciation and Extinction Rates for Phylogenies of Higher Taxa
Stadler Tanja, Bokma Folmer (2013), Estimating Speciation and Extinction Rates for Phylogenies of Higher Taxa, in SYSTEMATIC BIOLOGY, 62(2), 220-230.
How Can We Improve Accuracy of Macroevolutionary Rate Estimates?
Stadler Tanja (2013), How Can We Improve Accuracy of Macroevolutionary Rate Estimates?, in SYSTEMATIC BIOLOGY, 62(2), 321-329.
On the Need for Mechanistic Models in Computational Genomics and Metagenomics
Liberles David A., Teufel Ashley I., Liu Liang, Stadler Tanja (2013), On the Need for Mechanistic Models in Computational Genomics and Metagenomics, in GENOME BIOLOGY AND EVOLUTION, 5(10), 2008-2018.
Recovering speciation and extinction dynamics based on phylogenies
Stadler T. (2013), Recovering speciation and extinction dynamics based on phylogenies, in JOURNAL OF EVOLUTIONARY BIOLOGY, 26(6), 1203-1219.
The abrupt climate change at the Eocene-Oligocene boundary and the emergence of South-East Asia triggered the spread of sapindaceous lineages
Buerki Sven, Forest Felix, Stadler Tanja, Alvarez Nadir (2013), The abrupt climate change at the Eocene-Oligocene boundary and the emergence of South-East Asia triggered the spread of sapindaceous lineages, in ANNALS OF BOTANY, 112(1), 151-160.
Uncovering epidemiological dynamics in heterogeneous host populations using phylogenetic methods
Stadler Tanja, Bonhoeffer Sebastian (2013), Uncovering epidemiological dynamics in heterogeneous host populations using phylogenetic methods, in PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 368(1614), 20120198.
A Characterization of the Set of Species Trees that Produce Anomalous Ranked Gene Trees
Degnan James H., Rosenberg Noah A., Stadler Tanja (2012), A Characterization of the Set of Species Trees that Produce Anomalous Ranked Gene Trees, in IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS, 9(6), 1558-1568.
A New Method for Handling Missing Species in Diversification Analysis Applicable to Randomly or Nonrandomly Sampled Phylogenies
Cusimano N, Stadler T, Renner SS (2012), A New Method for Handling Missing Species in Diversification Analysis Applicable to Randomly or Nonrandomly Sampled Phylogenies, in SYSTEMATIC BIOLOGY, 61(5), 785-792.
A polynomial time algorithm for calculating the probability of a ranked gene tree given a species tree
Stadler Tanja, Degnan James H. (2012), A polynomial time algorithm for calculating the probability of a ranked gene tree given a species tree, in Algorithms for Molecular Biology, 7(1), 1.
Branch Lengths on Birth-Death Trees and the Expected Loss of Phylogenetic Diversity
Mooers A, Gascuel O, Stadler T, Li HY, Steel M (2012), Branch Lengths on Birth-Death Trees and the Expected Loss of Phylogenetic Diversity, in SYSTEMATIC BIOLOGY, 61(2), 195-203.
Distribution of branch lengths and phylogenetic diversity under homogeneous speciation models
Stadler T, Steel M (2012), Distribution of branch lengths and phylogenetic diversity under homogeneous speciation models, in JOURNAL OF THEORETICAL BIOLOGY, 297, 33-40.
Diversity-dependence brings molecular phylogenies closer to agreement with the fossil record
Etienne RS, Haegeman B, Stadler T, Aze T, Pearson PN, Purvis A, Phillimore AB (2012), Diversity-dependence brings molecular phylogenies closer to agreement with the fossil record, in PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 279(1732), 1300-1309.
Estimating the Basic Reproductive Number from Viral Sequence Data
Stadler T, Kouyos R, von Wyl V, Yerly S, Boni J, Burgisser P, Klimkait T, Joos B, Rieder P, Xie D, Gunthard HF, Drummond AJ, Bonhoeffer S (2012), Estimating the Basic Reproductive Number from Viral Sequence Data, in MOLECULAR BIOLOGY AND EVOLUTION, 29(1), 347-357.
Inferring Epidemic Contact Structure from Phylogenetic Trees
Leventhal GE, Kouyos R, Stadler T, von Wyl V, Yerly S, Boni J, Cellerai C, Klimkait T, Gunthard HF, Bonhoeffer S (2012), Inferring Epidemic Contact Structure from Phylogenetic Trees, in PLOS COMPUTATIONAL BIOLOGY, 8(3), -.
Macroevolutionary Dynamics and Historical Biogeography of Primate Diversification Inferred from a Species Supermatrix
Springer MS, Meredith RW, Gatesy J, Emerling CA, Park J, Rabosky DL, Stadler T, Steiner C, Ryder OA, Janecka JE, Fisher CA, Murphy WJ (2012), Macroevolutionary Dynamics and Historical Biogeography of Primate Diversification Inferred from a Species Supermatrix, in PLOS ONE, 7(11), -.
Response to Comment on "Impacts of the Cretaceous Terrestrial Revolution and KPg Extinction on Mammal Diversification"
Murphy WJ, Janecka JE, Stadler T, Eizirik E, Ryder OA, Gatesy J, Meredith RW, Springer MS (2012), Response to Comment on "Impacts of the Cretaceous Terrestrial Revolution and KPg Extinction on Mammal Diversification", in SCIENCE, 337(6090), 34.
The probability distribution of ranked gene trees on a species tree
Degnan JH, Rosenberg NA, Stadler T (2012), The probability distribution of ranked gene trees on a species tree, in MATHEMATICAL BIOSCIENCES, 235(1), 45-55.
UNEXPECTEDLY MANY EXTINCT HOMININS
Bokma F, van den Brink V, Stadler T (2012), UNEXPECTEDLY MANY EXTINCT HOMININS, in EVOLUTION, 66(9), 2969-2974.

Collaboration

Group / person Country
Types of collaboration
Department for Stochastics and Modeling, UPMC University Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Division of Infectious Diseases, University Hospital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Natural History Museum Stockholm Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Allan Wilson Centre for Molecular Ecology and Evolution, University of Auckland New Zealand (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
MEEGID 2014 Talk given at a conference A unified framework for phylodynamic inference of epidemic spread 10.12.2014 Bangkok, Thailand Stadler Tanja;
Radiation meeting, Botanical garden Zurich Talk given at a conference Detecting diversity dependent speciation using a birth-death model in BEAST2 13.06.2014 Zurich, Switzerland Stadler Tanja; Du Plessis Louis;
Jacques Monod Conference "From emerging to pandemic viruses: interplay between host ecology and viral evolution” Talk given at a conference How well does population genetics approximate epidemiological dynamics? 02.04.2014 Roscoff, France Du Plessis Louis; Stadler Tanja;


Self-organised

Title Date Place
SMIDDY 2013 13.09.2013 Zuerich, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Ebola Tagesanzeiger, Aargauer Zeitung, Basler Zeitung etc. International Italian-speaking Switzerland Western Switzerland German-speaking Switzerland 2014
Media relations: radio, television Ebola epidemic SRF, Bayern2 etc Italian-speaking Switzerland Western Switzerland International German-speaking Switzerland 2014
Talks/events/exhibitions National Future Day German-speaking Switzerland 2014
Talks/events/exhibitions Vortrag: Open House 2014 am D-BSSE, ETHZ German-speaking Switzerland 2014

Awards

Title Year
ETH Latsis Preis 2013
Zonta Preis Switzerland / Luxemburg 2013
Fellowship Wissenschaftskolleg Berlin 3 Month 2012
John Maynard Smith Prize 2012

Associated projects

Number Title Start Funding scheme
148522 Swiss HIV Cohort Study (SHCS) 01.01.2014 Cohort Studies Large

Abstract

RNA viruses are characterized by short generation time and high mutation rates. Therefore even over relatively short time spans epidemiological processes leave a fingerprint in the genetic structure of viral sequences sampled from the host population. As a consequence, both epidemiological and evolutionary processes can be inferred from virus sequences. However, until now epidemiological virus sequence data have been analyzed without assuming explicit epidemiological models, and therefore the quantification of key epidemiological parameters was not possible. The objective of this research proposal is to merge epidemiological and evolutionary models, so that both epidemiological and evolutionary parameters can be estimated on the basis of viral sequence data. The methodology will be available both as a Bayesian phylogenetic inference method and as a maximum likelihood phylogenetic method. The epidemiological models need to be formulated and analyzed in a stochastic framework rather than in the common deterministic framework as used by epidemiologists. Using the developed methodology, I will quantify epidemiological and evolutionary processes in HIV epidemics, followed by a large scale comparison of different viral epidemics. I will first investigate which treatment and intervention strategies had a significant impact on the epidemic spread of HIV in the past. In particular, I will apply the methods to sequence data of the Swiss HIV epidemic to identify to what extent different population groups (risk groups such as homosexuals, heterosexuals and intravenous drug users; or geographic groups) drive the HIV epidemics. The results will have the potential to support the efforts to design improved intervention strategies in the future. Second, I will address a key empirical paradox challenging our understanding of HIV evolutionary biology, namely the apparent incompatibility between the observed fast evolutionary rates obtained from within-host data and slow evolutionary rates obtained from between-host data. Applying the developed phylogenetic methods to HIV sequence data from the Swiss epidemic, I will quantify the risk group specific within- and between-host evolutionary rates. The quantification will allow me to support or reject alternative hypotheses explaining the rate differences. Third, the methodology will be applied to a variety of viral epidemics in order to recover the specific epidemiological dynamics. I plan to study Influenza virus, Dengue virus, Hepatitis C virus and Rhinovirus, viruses for which enough data is available to do phylogenetic analyses.
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