O'Toole, A. N. | Search bioRxiv

bioRxiv2021

Pango lineage designation and assignment using SARS-CoV-2 spike gene nucleotide sequences

More than 2 million SARS-CoV-2 genome sequences have been generated and shared since the start of the COVID-19 pandemic and constitute a vital information source that informs outbreak control, disease surveillance, and public health policy. The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. It is therefore important to understand how much information about Pango lineage status is contained in spike-only nucleotide sequences. Here we explore how Pango lineages might be reliably designated and assigned to spike-only nucleotide sequences. We survey the genetic diversity of such sequences, and investigate the information they contain about Pango lineage status. Although many lineages, including the main variants of concern, can be identified clearly using spike-only sequences, some spike-only sequences are shared among tens or hundreds of Pango lineages. To facilitate the classification of SARS-CoV-2 lineages using subgenomic sequences we introduce the notion of designating such sequences to a "lineage set", which represents the range of Pango lineages that are consistent with the observed mutations in a given spike sequence. These data provide a foundation for the development of software tools that can assign newly-generated spike nucleotide sequences to Pango lineage sets.

genomics↗

bioRxiv2020

Methylation-Based Age Estimation in a Wild Mouse

The age structure of populations, or the ageing rate of individuals, impacts aspects of ecology, epidemiology and conservation. Yet for many wild organisms, age is an inaccessible trait. In many cases measuring age or ageing rates in the wild requires molecular biomarkers of age. Epigenetic clocks based on DNA methylation have been shown to accurately estimate the age of humans and laboratory mice, but they also show variable ticking rates that are associated with mortality risk above and beyond that predicted by chronological age. Thus, epigenetic clocks are proving to be useful markers of both chronological and biological age, and they are beginning to be applied to wild mammals and birds. We have acquired strong evidence that an accurate clock is possible for the wood mouse Apodemus sylvaticus by adapting epigenetic information from the laboratory mouse (Mus musculus). Apodemus sylvaticus is a well-studied, common small mammal in the UK and Europe, which is amenable to large-scale experimental perturbations and longitudinal sampling of individuals across their lives. These features of the wood mouse system offer opportunities to disentangle causal relationships between ageing rates and environmental stress. Our wood mouse epigenetic clock is PCR-based, and so requires only tiny amounts of tissue accessible through non-destructive sampling. We quantified methylation using Oxford Nanopore sequencing technology and present a new bioinformatics pipeline for data analysis. We thus describe a new and generalizable system that should enable ecologists and other field biologists to go from small tissue samples to an epigenetic clock for their study animal, which will enable investigations of ageing in the wild which where previously inaccessible.

genetics↗