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Phylogenetic Analysis of SARS-CoV-2 Data Is Difficult.
Benoit Morel1, Pierre Barbera1, Lucas Czech2
1Computational Molecular Evolution Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany.
Molecular Biology and Evolution
|December 14, 2020
Summary
Inferring reliable SARS-CoV-2 phylogenies is challenging due to numerous sequences and few mutations. Phylogenetic analyses of COVID-19 evolution require cautious interpretation, especially with default tool settings.
Area of Science:
- Virology
- Computational Biology
- Epidemiology
Background:
- Daily publications analyze SARS-CoV-2 data, including phylogenies.
- Nextstrain.org provides regularly updated SARS-CoV-2 phylogenies.
- GISAID.org is a key data repository for virus sequences.
Purpose of the Study:
- To review difficulties in inferring reliable SARS-CoV-2 phylogenies.
- To evaluate the credibility of phylogenetic rooting methods.
- To assess the feasibility of automatic sequence classification.
Main Methods:
- Analysis of a quality-filtered subset of 8,736 SARS-CoV-2 sequences from May 5, 2020.
- Evaluation of phylogenetic inference challenges (sequence number vs. mutation rate).
- Assessment of rooting strategies (outgroups, computational methods) and mPTP classification.
Main Results:
- Inferring reliable phylogenies is difficult due to high sequence numbers and low mutation rates.
- Rooting phylogenies using bat/pangolin outgroups or computational methods lacks credibility.
- Automatic classification into subclasses using mPTP is not feasible for closely related sequences.
Conclusions:
- Phylogenetic methods offer some insight into SARS-CoV-2 evolution and spread.
- Results from phylogenetic analyses, especially with default settings, demand cautious interpretation.
- Downstream analyses based on inferred phylogenies also require careful consideration.
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