TreeFix-TP: Phylogenetic Error-Correction for Infectious Disease Transmission Network Inference

Pac Symp Biocomput. 2021:26:119-130.

Abstract

Many existing methods for estimation of infectious disease transmission networks use a phylogeny of the infecting strains as the basis for transmission network inference, and accurate network inference relies on accuracy of this underlying evolutionary history. However, phylogenetic reconstruction can be highly error prone and more sophisticated methods can fail to scale to larger outbreaks, negatively impacting downstream transmission network inference.We introduce a new method, TreeFix-TP, for accurate and scalable reconstruction of transmission phylogenies based on an error-correction framework. Our method uses intra-host strain diversity and host information to balance a parsimonious evaluation of the implied transmission network with statistical hypothesis testing on sequence data likelihood. The reconstructed tree minimizes the number of required disease transmissions while being as well supported by sequence data as the maximum likelihood phylogeny. Using a simulation framework for viral transmission and evolution and real data from ten HCV outbreaks, we demonstrate that error-correction with TreeFix-TP improves phylogenetic accuracy and outbreak source detection. Our results show that using TreeFix-TP can lead to significant improvement in transmission phylogeny inference and that its performance is robust to variations in transmission and evolutionary parameters. TreeFix-TP is freely available open-source from https://compbio.engr.uconn.edu/software/treefix-tp/.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computational Biology*
  • Computer Simulation
  • Humans
  • Phylogeny
  • Probability
  • Software*