A lung-specific mutational signature enables inference of viral and bacterial respiratory niche

Christopher Ruis; Thomas P. Peacock; Luis M. Polo; Diego Masone; Maria Soledad Alvarez; Angie S. Hinrichs; Yatish Turakhia; Ye Cheng; Jakob McBroome; Russell Corbett-Detig; Julian Parkhill; R. Andres Floto

doi:10.1099/mgen.0.001018

Volume 9, Issue 5

Short Communication

Open Access

A lung-specific mutational signature enables inference of viral and bacterial respiratory niche

Christopher Ruis^1,2,3, Thomas P. Peacock⁴, Luis M. Polo⁵, Diego Masone^5,6, Maria Soledad Alvarez⁷, Angie S. Hinrichs⁸, Yatish Turakhia⁹, Ye Cheng⁹, Jakob McBroome^8,10, Russell Corbett-Detig^8,10, Julian Parkhill² and R. Andres Floto^1,3,11
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Affiliations: ¹ Molecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK ² Department of Veterinary Medicine, University of Cambridge, Cambridge, UK ³ Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK ⁴ Department of Infectious Disease, Imperial College London, London, UK ⁵ Instituto de Histología y Embriología de Mendoza – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo, Mendoza, Argentina ⁶ Facultad de Ingeniería, Universidad Nacional de Cuyo, Mendoza, Argentina ⁷ Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo (UNCuyo), Mendoza, Argentina ⁸ Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA ⁹ Department of Electrical and Computer Engineering, University of California San Diego, San Diego, CA, USA ¹⁰ Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA ¹¹ Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK
*Correspondence: R. Andres Floto, [email protected] *Correspondence: Julian Parkhill, [email protected] *Correspondence: Christopher Ruis, [email protected]
Published: 15 May 2023 https://doi.org/10.1099/mgen.0.001018

Abstract

Exposure to different mutagens leaves distinct mutational patterns that can allow inference of pathogen replication niches. We therefore investigated whether SARS-CoV-2 mutational spectra might show lineage-specific differences, dependent on the dominant site(s) of replication and onwards transmission, and could therefore rapidly infer virulence of emergent variants of concern (VOCs). Through mutational spectrum analysis, we found a significant reduction in G>T mutations in the Omicron variant, which replicates in the upper respiratory tract (URT), compared to other lineages, which replicate in both the URT and lower respiratory tract (LRT). Mutational analysis of other viruses and bacteria indicates a robust, generalizable association of high G>T mutations with replication within the LRT. Monitoring G>T mutation rates over time, we found early separation of Omicron from Beta, Gamma and Delta, while mutational patterns in Alpha varied consistent with changes in transmission source as social restrictions were lifted. Mutational spectra may be a powerful tool to infer niches of established and emergent pathogens.

Received: 05/01/2023
Accepted: 20/03/2023
Published Online: 15/05/2023

Keyword(s): genomics , mutational spectrum , SARS-CoV-2 and transmission

Funding

This study was supported by the:

Centers for Disease Control and Prevention Foundation (Award BAA 200-2021-11554)
- Principle Award Recipient: RussellCorbett-Detig
G2P-UK National Virology Consortium funded by the MRC (Award MR/W005611/1)
- Principle Award Recipient: ThomasP Peacock
UK CF Trust (Award Innovation Hub Award 001; Strategic Research Centre SRC010)
- Principle Award Recipient: R.Andres Floto
Fondation Botnar (Award Programme grant 6063)
- Principle Award Recipient: R.Andres Floto
Wellcome Trust (Award 107032/Z/15/Z)
- Principle Award Recipient: R.Andres Floto

This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

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A lung-specific mutational signature enables inference of viral and bacterial respiratory niche

M Gen 9, 001018 (2023); https://doi.org/10.1099/mgen.0.001018

/content/journal/mgen/10.1099/mgen.0.001018

Volume 9, Issue 5

Short Communication

Open Access

A lung-specific mutational signature enables inference of viral and bacterial respiratory niche

Abstract

Funding

Supplementary material 1

Supplementary material 2

Supplementary material 3

Supplementary material 4

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