The overall goal of this project is to develop and validate novel methods to perform joint inference from combined epidemiologic and genetic data. This inference methodology seeks to provide estimates of fundamental transmission parameters, such as RO, as well as provide estimates of unobserved transmission trees and unobserved counts of susceptible, infected and recovered individuals in the population through time. We focus on two common scenarios. In the first, we target densely sampled, but localized, epidemiologic and genetic data, in which the person, place and time are known, and in which pathogen genetic samples are obtained. These sorts of datasets are commonly generated during transmission studies in households, schools, and similar settings, but also in analyses of novel outbreaks such as SARS or H7N9. Our inference framework seeks to estimate host-to-host transmission networks from combined epidemiologic and genetic data. In the second scenario, we target sparsely sampled, but broader in scope, epidemiologic and genetic data, in which we observe a time series of case reports and sparsely sampled pathogen genetic sequences. In this inference framework, we seek to model population-level transmission processes from a relatively small samples of cases. This framework utilizes coalescent theory to extrapolate from sampled genetic sequences to population-level dynamics. In implementation, we plan to utilize sophisticated inference methodology that combines Markov chain Monte Carlo (MCMC) and sequential Monte Carlo (SMC) approaches in what's termed particle MCMC (PMCMC). We plan to utilize these novel inference methods to investigate transmission heterogeneity and local transmission structure in influenza, phenomena that have been difficult to fully analyze without a combined epidemiologic and genetic inference framework in place.

Public Health Relevance

As sequencing becomes increasingly ubiquitous, the ability to combine epidemiologic and genetic data will become increasingly relevant, and appropriate statistical tools will be become increasingly necessary. The methods developed in this project will have direct public health relevance in that they will allow better estimates of critical transmission parameters, such as RO, better reveal risk factors for transmission and provide knowledge of transmission heterogeneity and local transmission structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54GM111274-01
Application #
8796474
Study Section
Special Emphasis Panel (ZGM1-BBCB-5 (MI))
Project Start
Project End
Budget Start
2014-09-12
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$325,278
Indirect Cost
$119,097
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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