TreeKnit: Inferring ancestral reassortment graphs of influenza viruses

PLoS Comput Biol. 2022 Aug 19;18(8):e1010394. doi: 10.1371/journal.pcbi.1010394. eCollection 2022 Aug.

Abstract

When two influenza viruses co-infect the same cell, they can exchange genome segments in a process known as reassortment. Reassortment is an important source of genetic diversity and is known to have been involved in the emergence of most pandemic influenza strains. However, because of the difficulty in identifying reassortment events from viral sequence data, little is known about their role in the evolution of the seasonal influenza viruses. Here we introduce TreeKnit, a method that infers ancestral reassortment graphs (ARG) from two segment trees. It is based on topological differences between trees, and proceeds in a greedy fashion by finding regions that are compatible in the two trees. Using simulated genealogies with reassortments, we show that TreeKnit performs well in a wide range of settings and that it is as accurate as a more principled bayesian method, while being orders of magnitude faster. Finally, we show that it is possible to use the inferred ARG to better resolve segment trees and to construct more informative visualizations of reassortments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Genome, Viral / genetics
  • Humans
  • Influenza, Human*
  • Orthomyxoviridae* / genetics
  • Phylogeny
  • Reassortant Viruses / genetics

Grants and funding

This work was funded by SNF (310030_188547) to RAN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.