High-resolution Genomic Surveillance of 2014 Ebolavirus Using Shared Subclonal Variants.
BACKGROUND
Viral outbreaks, such as the 2014 ebolavirus, can spread rapidly and have complex evolutionary dynamics, including coinfection and bulk transmission of multiple viral populations. Genomic surveillance can be hindered when the spread of the outbreak exceeds the evolutionary rate, in which case consensus approaches will have limited resolution. Deep sequencing of infected patients can identify genomic variants present in intrahost populations at subclonal frequencies (i.e. <50%). Shared subclonal variants (SSVs) can provide additional phylogenetic resolution and inform about disease transmission patterns.


METHODS
We use metrics from population genetics to analyze data from the 2014 ebolavirus outbreak in Sierra Leone and identify phylogenetic signal arising from SSVs. We use methods derived from information theory to measure a lower bound on transmission bottleneck size.


CONCLUSIONS
We identify several SSV that shed light on phylogenetic relationships not captured by consensus-based analyses. We find that transmission bottleneck size is larger than one founder population, yet significantly smaller than the intrahost effective population. Our results demonstrate the important role of shared subclonal variants in genomic surveillance.
Department of Physics and Department of Systems Biology, Columbia University, New York, New York, USA.
Kevin J
KJ
Emmett
Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA.
Albert
A
Lee
Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA.
Hossein
H
Khiabanian
Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA.
Raul
R
Rabadan
ebolavirus; genomic surveilance; intrahost variants; transmission bottleneck