Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add filters

Language
Document Type
Year range
1.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.09.28.509985

ABSTRACT

Summary Treenome Browser is a web browser tool to interactively visualize millions of genomes alongside huge phylogenetic trees. Availability and Implementation Treenome Browser for SARS-CoV-2 can be accessed at cov2tree.org , or at taxonium.org for user-provided trees. Source code and documentation are available at github.com/theosanderson/taxonium and docs.taxonium.org/en/latest/treenome.html . Contact alex.kramer@ucsc.edu , rucorbet@ucsc.edu

2.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.06.03.494608

ABSTRACT

The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. Previous web-based tools for phylogenetic exploration were not able to directly scale to this size of tree. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes. Taxonium allows visualisation of mutation-annotated trees, where the genotypes at each internal node are indicated, and also links each node to associated metadata. An optional server-side backend permits rapid loading for widely used datasets, while a client-only mode allows the exploration of niche or sensitive data. Taxonium is an open-source tool which can be applied to any large tree. We provide an application for exploring a public tree of more than five million SARS-CoV-2 sequences at http://cov2tree.org, the broader Taxonium tool at http://taxonium.org, and source code at https://github.com/theosanderson/taxonium.

3.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.04.20.488895

ABSTRACT

Two mutations occurred in SARS-CoV-2 early during the COVID-19 pandemic that have come to define circulating virus lineages: first a change in the spike protein (D614G) that defines the B.1 lineage and second, a double substitution in the nucleocapsid protein (R203K, G204R) that defines the B.1.1 lineage, which has subsequently given rise to three Variants of Concern: Alpha, Gamma and Omicron. While the latter mutations appear unremarkable at the protein level, there are dramatic implications at the nucleotide level: the GGG[->]AAC substitution generates a new Transcription Regulatory Sequence (TRS) motif, driving SARS-CoV-2 to express a novel subgenomic mRNA (sgmRNA) encoding a truncated C-terminal portion of nucleocapsid (N.iORF3), which is an inhibitor of type I interferon production. We find that N.iORF3 also emerged independently within the Iota variant, and further show that additional TRS motifs have convergently evolved to express novel sgmRNAs; notably upstream of Spike within the nsp16 coding region of ORF1b, which is expressed during human infection. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level, reminiscent of eukaryotic evolution. Greater attention to this aspect in the assessment of emerging strains of SARS-CoV-2 is warranted.

4.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.03.08.481609

ABSTRACT

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While from a case-number perspective these interventions succeeded in reducing the absolute number of cases of SARS-CoV-2 in the UK, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of those SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

5.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.10.27.465994

ABSTRACT

Phylogenetic trees are an important tool for interpreting sequenced genomes, and their interrelationships. Estimating the date associated with each node of such a phylogeny creates a “time tree”, which can be especially useful for visualising and analysing evolution of organisms such as viruses. Several tools have been developed for time-tree estimation, but the sequencing explosion in response to the SARS-CoV-2 pandemic has created phylogenies so large as to prevent the application of these previous approaches to full datasets. Here we introduce Chronumental, a tool that can rapidly infer time trees from phylogenies featuring large numbers of nodes. Chronumental uses stochastic gradient descent to identify lengths of time for tree branches which maximise the evidence lower bound under a probabilistic model, implemented in a framework which can be compiled into XLA for rapid computation. We show that Chronumental scales to phylogenies featuring millions of nodes, with chronological predictions made in minutes, and is able to accurately predict the dates of nodes for which it is not provided with metadata.

6.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.10.14.21264847

ABSTRACT

Public SARS-CoV-2 genomes from the Delta lineage show complex and confusing patterns of mutations at Spike codon 142, and at another nearby position, Spike codon 95. It has been hypothesised that these represent recurrent mutations with interesting evolutionary dynamics, and that these mutations may affect viral load. Here we show that these patterns, and the relationship with viral load, are artifacts of sequencing difficulties in this region of the Delta genome caused be a deletion in the binding site for the 72_RIGHT primer of the ARTIC V3 schema. Spike G142D should be considered a lineage-defining mutation of Delta.

7.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.22.21257633

ABSTRACT

Despite regional successes in controlling the SARS-CoV-2 pandemic, global cases have reached an all time high in April 2021 in part due to the evolution of more transmissible variants. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 62 different lineages in each of 315 English local authorities between September 2020 and April 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a singular jump in transmissibility of the B.1.1.7 lineage. B.1.1.7 grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown eventually suppressed B.1.1.7 and eliminated nearly all other lineages in early 2021. However, a series of variants (mostly containing the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. Accounting for sustained introductions, however, indicates that their transmissibility is unlikely to exceed that of B.1.1.7. Finally, B.1.617.2 was repeatedly introduced to England and grew rapidly in April 2021, constituting approximately 40% of sampled COVID-19 genomes on May 15.

SELECTION OF CITATIONS
SEARCH DETAIL