Samuel M. Nicholls
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- COVID-19 Clinical Research Studies
- Gene expression and cancer classification
- COVID-19 epidemiological studies
- SARS-CoV-2 detection and testing
- Gut microbiota and health
- vaccines and immunoinformatics approaches
- Bioinformatics and Genomic Networks
- Animal Virus Infections Studies
- Microbial Metabolic Engineering and Bioproduction
- Microbial Community Ecology and Physiology
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Genomics and Rare Diseases
- Machine Learning in Bioinformatics
- Metabolomics and Mass Spectrometry Studies
- Biomedical Text Mining and Ontologies
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Genetic Associations and Epidemiology
- Mosquito-borne diseases and control
- Cell Image Analysis Techniques
- Long-Term Effects of COVID-19
University of Birmingham
2017-2024
Czech Academy of Sciences, Institute of Microbiology
2024
Genomics England
2021
COVID-19 Genomics UK Consortium
2021
Aberystwyth University
2016-2020
KU Leuven
2016-2020
University of Oxford
2020
Children's Health Ireland at Crumlin
2020
Institute of Biological, Environmental and Rural Sciences
2016-2017
Wellcome Sanger Institute
2016
Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive a selective advantage but may also be due to random founder effect. We investigate hypothesis for positive selection in United Kingdom using more than 25,000 whole genome sequences. Despite availability large dataset, well represented by both 614 variants, not all approaches showed conclusive signal selection. Population genetic analysis indicates that 614G increases relative 614D manner...
Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in world. Because limited available data, assessments impact nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced reproduction number from >3 to 1 1.6 São Paulo and Rio de Janeiro. Sequencing 427 new genomes analysis geographically representative genomic dataset identified >100...
We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase affinity the ACE2 confer antibody escape. In vitro, we show that, although itself is not an evasion mechanism, it increases infectivity associated with enhanced incorporation cleaved into virions. able partially rescue proteins that have acquired Y453F escape...
Lineage dynamics The scale of genome-sequencing efforts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented. United Kingdom has contributed more than 26,000 sequences to this effort. This volume data allowed du Plessis et al. develop a detailed picture the influxes virus reaching U.K. shores as pandemic developed during first months 2020 (see Perspective by Nelson). Before lockdown, high travel volumes and few restrictions on international 1000 lineages become...
Patterns and bottlenecks A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some these have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. undertaken in-depth sequencing more than 1000 hospital patients' isolates to find out how virus is mutating within individuals. Overall, there seem be consistent reproducible patterns within-host diversity. The...
Long sequencing reads are information-rich: aiding de novo assembly and reference mapping, consequently have great potential for the study of microbial communities. However, best approaches analysis long-read metagenomic data unknown. Additionally, rigorous evaluation bioinformatics tools is hindered by a lack from validated samples with known composition.We sequenced 2 commercially available mock communities containing 10 species (ZymoBIOMICS Microbial Community Standards) Oxford Nanopore...
Summary Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive a selective advantage but may also be due to random founder effect. We investigate hypothesis for positive selection in United Kingdom using more than 25,000 whole genome sequences. Despite availability large data set, well represented by both 614 variants, not all approaches showed conclusive signal selection. Population genetic analysis indicates that 614G increases relative 614D...
Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but understudied. Many case studies have been published which describe one or a small number long-term infected individuals no study has combined these sequences into cohesive dataset. This work aims to rectify this and genomics patient group through combination literature searches as well identifying new series directly from...
Abstract Background The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools resources, advocate greater openness, interoperability, accessibility, reproducibility in public health microbial bioinformatics. In face current pandemic, PHA4GE has identified need fit-for-purpose, open-source SARS-CoV-2...
ABSTRACT In the field of observation, chance favours only prepared mind (Pasteur). Impressive developments in genomics have led microbiology to its third “Golden Age”. However, conventional metagenomics strategies necessitate retrograde transfer samples from extreme or remote environments for later analysis, rendering powerful insights gained retrospective nature, striking a contrast with Pasteur’s dictum. Here we implement highly portable USB-based nanopore DNA sequencing platforms coupled...
Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed AMR genotype, while immunological massive and escalating T-cell activation. These were both SARS-CoV-2 P. specific, bystander activated, which may have contributed this patient’s persistent symptoms radiological changes.
Abstract Extensive global sampling and whole genome sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to characterise its spread, identify mutations that may increase transmission or enable escape therapies vaccines. Two important components viral spread are how frequently variants arise within individuals, likely they be transmitted. Here, we within-host diversity SARS-CoV-2, extent which genetic is transmitted, by quantifying variant frequencies in 1390 clinical samples...
The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 13 million sequences shared publicly at time writing. This wealth sequence provides important context for interpreting local outbreaks. However, placing interest into national and international is difficult given size global dataset. Often outbreak investigations genomic surveillance efforts require running similar analyses again on latest dataset producing reports. We developed civet (cluster...
Background: Long sequencing reads are information-rich: aiding de novo assembly and reference mapping, consequently have great potential for the study of microbial communities. However, best approaches analysis long-read metagenomic data unknown. Additionally, rigorous evaluation bioinformatics tools is hindered by a lack from validated samples with known composition. Methods: We sequenced two commercially-available mock communities containing ten species (ZymoBIOMICS Microbial Community...
Abstract Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in world. Due to limited available data, assessments impact non-pharmaceutical interventions (NPIs) on virus transmission and epidemic spread remain challenging. We investigate NPIs using epidemiological, mobility genomic data. Mobility-driven models for São Paulo Rio de Janeiro cities show that reproduction number ( R t ) reached below 1 following but slowly increased values between 1.3 (1.0–1.6). Genome...
Abstract The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure this through analysis 50,887 SARS-CoV-2 genomes, including 26,181 from UK sampled throughout country’s first wave infection. Using large-scale phylogenetic analyses, combined with epidemiological travel data, quantify size, spatio-temporal origins persistence genetically-distinct transmission...
Abstract Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough inform outbreak response, and cheaply justify dense sampling of even large epidemics. With increased availability sequencing is agile networks facilities collaborate on the analysis genomic data. In response ongoing SARS-CoV-2 pandemic in United Kingdom, COVID-19 Genomics UK (COG-UK) consortium was formed with aim...
Population-level genetic variation enables competitiveness and niche specialization in microbial communities. Despite the difficulty culturing many microbes from an environment, we can still study these communities by isolating sequencing DNA directly environment (metagenomics). Recovering genomic sequences of all isoforms a given gene across organisms metagenomic sample would aid evolutionary ecological insights into ecosystems with potential benefits for medicine biotechnology. A...
The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatic tools resources, advocate greater openness, interoperability, accessibility reproducibility in public health microbial bioinformatics. In face current pandemic, PHA4GE has identified clear present need fit-for-purpose, open source SARS-CoV-2...
Summary We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single nucleotide polymorphisms deletions that are characteristic B.1.1.7 variant concern, but lack full complement lineage-defining mutations. Instead, remainder their share contiguous genetic variation with non-B.1.1.7 circulating same geographic area at time as recombinants. In four instances there was onward...
Abstract Elucidation of population-level diversity microbiomes is a significant step towards complete understanding the evolutionary, ecological and functional importance microbial communities. Characterizing this requires recovery exact DNA sequence (haplotype) each gene isoform from every individual present in community. To address this, we Hansel Gretel : freely-available data structure algorithm, providing software package that reconstructs most likely haplotypes metagenomes. We...