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Journal article
Genetic grouping of SARS-CoV-2 coronavirus sequences using informative subtype markers for pandemic spread visualization
PLoS computational biology, v 16(9), pp e1008269-e1008269
Sep 2020
PMID: 32941419
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM (Jupyter notebook), https://github.com/EESI/ncov_ism (command line tool) and via an interactive website at https://covid19-ism.coe.drexel.edu/.
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Details
- Title
- Genetic grouping of SARS-CoV-2 coronavirus sequences using informative subtype markers for pandemic spread visualization
- Creators
- Zhengqiao Zhao - Drexel UniversityBahrad A Sokhansanj - Drexel UniversityCharvi Malhotra - Drexel UniversityKitty Zheng - Drexel UniversityGail L Rosen - Drexel University
- Publication Details
- PLoS computational biology, v 16(9), pp e1008269-e1008269
- Publisher
- Public LIbrary of Science (PLOS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Electrical and Computer Engineering; College of Medicine
- Web of Science ID
- WOS:000573853000004
- Scopus ID
- 2-s2.0-85092211614
- Other Identifier
- 991019168611504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemical Research Methods
- Mathematical & Computational Biology