A comprehensive study of the phylodynamics of SARS-CoV-2 in Europe

Cecilia Valenzuela Agüí

Supervised by Dr. Timothy Vaughan, Prof. Dr. Tanja Stadler, Sarah Nadeau. Computational Biology Group

CBB Master’s Thesis Project Outline September 1, 2020 - March 16, 2021

This project will focus on the spatial dynamics of the early spread of SARS-CoV-2 in Europe. We will apply a novel approach based on the Multi-type Birth Death phylodynamic model to infer structured population dynamics jointly with between-subpopulation transmission rates from viral genome sequences. The inferred epidemic trajectories for the combined outbreak responsible for the observed sequence data will allow us to better understand the entry into and early spread of SARS-CoV-2 in Europe.

For the analysis, we will use the software package BEAST2, a tool for Bayesian evolutionary analysis of molecular sequences using MCMC. The sequence data will be gathered from GISAID publicly available sequences.

i. Main Tasks

1. Create a current and representative sequence alignment for the early phase of COVID-19 pandemic from available SARS-CoV sequences. This includes sequence selection, curation and alignment.
2. Use travel and geographical data as the basis for informative priors on migration rates, this could significantly improve the precision and accuracy of the results.
3. Reconstruction of a partial transmission tree of the early pandemic, including inferred geographic location of ancestral lineages.
4. Inference of multi-type epidemic trajectories, allowing us to directly infer the number SARS-CoV-2 of introductions into a country.

ii. Tools

• Bayesian Analysis - BEAST2 v2.6.3 and related software
• IDE - IntelliJ IDEA 2020.2.1 (Community Edition)
• Pre and post analysis - R?
• Reference management - endNote X9.3.3
• Version Control - Git and Gitlab SARS-CoV-2 EU phylodynamics repo
• Mackbook Pro 2.2 GHz 6-Core Intel Core i7
• ETH Euler cluster

iii. Workflow

• Analysis

  • XML definition with BEAUti inside IntelliJ
  • Run analysis using BEAST2 on Euler with .jar file from IntelliJ project
  • Analyze results with Tracer, R...?

• Documentation

  • Gitlab repository: Analysis specs .md file for each analysis in analysis folder. README files for each folder with file information.

  • Wiki Gitlab Repository: Research Plan, Sources, Analysis Specs Template, useful guidelines and theoretical topics description.

• Reference management with endNote X9, annotating and research notes in the pdf and in the reference itself. endNote compressed library backup in gitlab repo.

• SARS-CoV-2 EU phylodynamics Gitlab repository

Folder	Description
/alignments	Sequence data and alignments used in the analysis
/analysis	XML files from the analysis and Analysis specs .md file with all the information about the analysis steps
/results	Processed results from the analysis
/workflow	Snakefile and scripts for workflow
/reports	PDFs documents and reports

• Local File system

Folder	Description
/Master's Thesis	Local copy of gitlab repo and wiki, endNote library and other organisational files
/mt-analysis	All files from analysis, raw and processed results. One subfolder for each analysis. Important for reproducibility files are copied to gitlab repository.
/mt-beast-dev	BEAST2, BDMM-Prime and other packages for IntelliJ project.

• Backups

Weekly, every Friday. Backup of Master's Thesis, mt-analysis, mt-beast-dev local folders to Lacie hard drive and important results to my bs-home folder.