Imperial College London


Faculty of MedicineSchool of Public Health

Senior Lecturer



+44 (0)20 7594 1933e.volz Website




UG10Norfolk PlaceSt Mary's Campus






BibTex format

author = {Volz, E and Romero-Severson, E and Leitner, TK},
doi = {molbev/msx077},
journal = {Molecular Biology and Evolution},
pages = {1276--1288},
title = {Phylodynamic inference across epidemic scales},
url = {},
volume = {34},
year = {2017}

RIS format (EndNote, RefMan)

AB - Within-host genetic diversity and large transmission bottlenecks confound phylodynamic inference ofepidemiological dynamics. Conventional phylodynamic approaches assume that nodes in a time-scaledpathogen phylogeny correspond closely to the time of transmission between hosts that are ancestral tothe sample. However, when hosts harbour diverse pathogen populations, node times can substantiallypre-date infection times. Imperfect bottlenecks can cause lineages sampled in different individuals tocoalesce in unexpected patterns. To address realistic violations of standard phylodynamic assumptionswe developed a new inference approach based on a multi-scale coalescent model, accounting for nonlinearepidemiological dynamics, heterogeneous sampling through time, non-negligible genetic diversity ofpathogens within hosts, and imperfect transmission bottlenecks. We apply this method to HIV-1 andEbola virus outbreak sequence data, illustrating how and when conventional phylodynamic inference maygive misleading results. Within-host diversity of HIV-1 causes substantial upwards bias in the numberof infected hosts using conventional coalescent models, but estimates using the multi-scale model havegreater consistency with reported number of diagnoses through time. In contrast, we find that within-host diversity of Ebola virus has little influence on estimated numbers of infected hosts or reproductionnumbers, and estimates are highly consistent with the reported number of diagnoses through time.The multi-scale coalescent also enables estimation of within-host effective population size using singlesequences from a random sample of patients. We find within-host population genetic diversity of HIV-1p17 to be 2Nμ= 0.012(95% CI:0.0066−0.023), which is lower than estimates based on HIV envelopeserial sequencing of individual patients.
AU - Volz,E
AU - Romero-Severson,E
AU - Leitner,TK
DO - molbev/msx077
EP - 1288
PY - 2017///
SN - 1537-1719
SP - 1276
TI - Phylodynamic inference across epidemic scales
T2 - Molecular Biology and Evolution
UR -
UR -
VL - 34
ER -