bioRxiv ScienceSearch

bioRxiv · 10.1101/050211

Assessing the accuracy of Approximate Bayesian Computation approaches to infer epidemiological parameters from phylogenies

Abstract

Phylodynamics typically rely on likelihood-based methods to infer epidemiological parameters from dated phylogenies. These methods are essentially based on simple epidemiological models because of the difficulty in expressing the likelihood function analytically. Computing this function numerically raises additional challenges, especially for large phylogenies. Here, we use Approximate Bayesian Computation (ABC) to circumvent these problems. ABC is a likelihood-free method of parameter inference, based on simulation and comparison between target data and simulated data, using summary statistics. We simulated target trees under several epidemiological scenarios in order to assess the accuracy of ABC methods for inferring epidemiological parameter such as the basic reproduction number (R0), the mean duration of infection, and the effective host population size. We designed many summary statistics to capture the information in a phylogeny and its corresponding lineage-through-time plot. We then used the simplest ABC method, called rejection, and its modern derivative complemented with adjustment of the posterior distribution by regression. The availability of machine learning techniques including variable selection, motivated us to compute many summary statistics on the phylogeny. We found that ABC-based inference reaches an accuracy comparable to that of likelihood-based methods for birth-death models and can even outperform existing methods for more refined models and large trees. By re-analysing data from the early stages of the recent Ebola epidemic in Sierra Leone, we also found that ABC provides more realistic estimates than the likelihood-based methods, for some parameters. This work shows that the combination of ABC-based inference using many summary statistics and sophisticated machine learning methods able to perform variable selection is a promising approach to analyse large phylogenies and non-trivial models.

Explore related subjects

Keep this discovery

BibTeXRIS

Emma Saulnier, Samuel Alizon, Olivier Gascuel. 2016-04-26. Assessing the accuracy of Approximate Bayesian Computation approaches to infer epidemiological parameters from phylogenies. https://doi.org/10.1101/050211

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

iCARE: An R Package to Build and Apply Absolute Risk Models

This report describes a R package, called the Individualized Coherent Absolute Risk Estimation (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individuals risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different populations by specifying three input arguments: (1) a model for relative risk, (2) an age-specific disease incidence rate, (3) the distribution of risk factors for the population of interest. The tool can handle missing information on risk factors for individuals for whom risks are to be predicted using a coherent approach where all estimates are derived from a single model after appropriate model averaging. The software allows single nucleotide polymorphisms (SNPs) to be incorporated into the model using published odds ratios and allele frequencies. The validation component of the software implements the methods for evaluation of model calibration, discrimination and risk-stratification based on independent validation datasets. We provide an illustration of the utility of iCARE for building, validating and applying absolute risk models using breast cancer as an example.

Bioinformatics

deSPI: efficient classification of metagenomic reads with lightweight de Bruijn graph-based reference indexing

SummaryIn metagenomic studies, fast and effective tools are on wide demand to implement taxonomy classification for upto billions of reads. Herein, we propose deSPI, a novel read classification method that classifies reads by recognizing and analyzing the matches between reads and reference with de Bruijn graph-based lightweight reference indexing. deSPI has faster speed with relatively small memory footprint, meanwhile, it can also achieve higher or similar sensitivity and accuracy.\n\nAvailabilitythe C++ source code of deSPI is available at https://github.com/hitbc/deSPI\n\nContactydwang@hit.edu.cn\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

Bioinformatics

De novo assembly of viral quasispecies using overlap graphs

A viral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high mutation and recombination rates, high-quality reference genomes are often not available at the time of a new disease outbreak. We present SAVAGE, a computational tool for reconstructing individual haplotypes of intrahost virus strains without the need for a high-quality reference genome. SAVAGE makes use of either FM-index based data structures or ad-hoc consensus reference sequence for constructing overlap graphs from patient sample data. In this overlap graph, nodes represent reads and/or contigs, while edges reflect that two reads/contigs, based on sound statistical considerations, represent identical haplotypic sequence. Following an iterative scheme, a new overlap assembly algorithm that is based on the enumeration of statistically well-calibrated groups of reads/contigs then efficiently reconstructs the individual haplotypes from this overlap graph. In benchmark experiments on simulated and on real deep coverage data, SAV-AGE drastically outperforms generic de novo assemblers as well as the only specialized de novo viral quasispecies assembler available so far. When run on ad-hoc consensus reference sequence, SAVAGE performs very favorably in comparison with state-of-the-art reference genome guided tools. We also apply SAVAGE on two deep coverage samples of patients infected by the Zika and the hepatitis C virus, respectively, which sheds light on the genetic structures of the respective viral quasispecies.

Bioinformatics