[Paper Review] Phylogenetic study of 2019-nCoV by using alignment-free method

Yan-Wei Gao, Li T+1 more|arXiv (Cornell University)|Mar 2, 2020

SARS-CoV-2 and COVID-19 Research24 references4 citations

TL;DR

This study uses the IC-PIC alignment-free method to analyze 2019-nCoV phylogeny based on RNA sequence correlations, revealing that 2019-nCoV belongs to the Sarbecovirus subgenus of Betacoronavirus and likely originated in bats with pangolins as a possible intermediate host. The analysis suggests early global spread before the Wuhan outbreak, supported by topology consistency with biological systematics and robust root placement using multiple out-groups.

ABSTRACT

The origin and early spread of 2019-nCoV is studied by phylogenetic analysis using IC-PIC alignment-free method based on DNA/RNA sequence information correlation (IC) and partial information correlation (PIC). The topology of phylogenetic tree of Betacoronavirus is remarkably consistent with biologist's systematics, classifies 2019-nCoV as Sarbecovirus of Betacoronavirus and supports the assumption that these novel viruses are of bat origin with pangolin as one of the possible intermediate hosts. The novel virus branch of phylogenetic tree shows location-virus linkage. The placement of root of the early 2019-nCoV tree is studied carefully in Neighbor Joining consensus algorithm by introducing different out-groups (Bat-related coronaviruses, Pangolin coronaviruses and HIV viruses etc.) and comparing with UPGMA consensus trees. Several oldest branches (lineages) of the 2019-nCoV tree are deduced that means the COVID-19 may begin to spread in several regions in the world before its outbreak in Wuhan.

Motivation & Objective

• To determine the phylogenetic placement of 2019-nCoV within the Betacoronavirus genus using alignment-free sequence analysis.
• To investigate the evolutionary origin of 2019-nCoV, particularly the role of bats and pangolins as potential reservoirs.
• To assess the timing and geographic spread of early 2019-nCoV lineages by analyzing root placement in phylogenetic trees.
• To validate the robustness of tree topology using multiple out-groups and consensus algorithms (Neighbor Joining and UPGMA).
• To explore the presence of location-virus linkage in the early branching patterns of the 2019-nCoV phylogenetic tree.

Proposed method

• Application of the IC-PIC (Information Correlation and Partial Information Correlation) alignment-free method to compare RNA sequences of 2019-nCoV and related coronaviruses.
• Use of DNA/RNA sequence information correlation (IC) and partial information correlation (PIC) to quantify evolutionary distances without sequence alignment.
• Construction of phylogenetic trees using the Neighbor Joining algorithm with multiple out-groups, including bat- and pangolin-related coronaviruses and HIV.
• Comparison of Neighbor Joining trees with UPGMA consensus trees to validate root placement and tree topology.
• Systematic evaluation of root placement by testing different out-groups to infer the most reliable evolutionary origin.
• Analysis of early branches in the 2019-nCoV tree to detect potential geographic clustering or location-virus linkage.

Experimental results

Research questions

• RQ1 Where does 2019-nCoV stand phylogenetically within the Betacoronavirus genus, and which subgenus does it belong to?
• RQ2 What is the evolutionary origin of 2019-nCoV, and which animal species—bats or pangolins—serve as the most likely reservoir or intermediate host?
• RQ3 Is there evidence of early viral spread in multiple global regions before the recognized outbreak in Wuhan?
• RQ4 How robust is the phylogenetic tree topology when different out-groups are used for root placement?
• RQ5 To what extent do early viral lineages show geographic clustering or location-virus linkage?

Key findings

• 2019-nCoV is classified as a Sarbecovirus within the Betacoronavirus genus, consistent with biological systematics.
• The IC-PIC method produced a phylogenetic tree topology that aligns with established virological classifications, supporting the reliability of the alignment-free approach.
• The analysis supports a bat origin for 2019-nCoV, with pangolins identified as a possible intermediate host.
• Several of the oldest branches in the 2019-nCoV tree suggest that the virus may have begun spreading in multiple global regions prior to the Wuhan outbreak.
• Root placement was stable and consistent across different out-groups, including bat- and pangolin-related coronaviruses, enhancing confidence in the evolutionary inference.
• The presence of location-virus linkage in early branches indicates potential regional spread patterns in the initial phase of the pandemic.