scholarly journals Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2

2021 ◽  
Author(s):  
Jingsong Zhang ◽  
Yang Zhang ◽  
Junyan Kang ◽  
Shuiye Chen ◽  
Yongqun He ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Genome ◽  
Immune Escape ◽  
Alternative Hypothesis ◽  
Evolutionary Process ◽  
P Value ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
The United Kingdom

The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p value<E-44). In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5'UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly enhanced the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

scholarly journals Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingsong Zhang ◽  
Yang Zhang ◽  
Jun-Yan Kang ◽  
Shuiye Chen ◽  
Yongqun He ◽  
...  
Keyword(s):  
United Kingdom ◽  
Viral Replication ◽  
Viral Genome ◽  
Immune Escape ◽  
Alternative Hypothesis ◽  
Evolutionary Process ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
The United Kingdom

AbstractThe presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here, we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole-genome represents a large number of potential co-mutations. In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5′UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

scholarly journals Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Reuben J. Pengelly ◽  
William Tapper ◽  
Jane Gibson ◽  
Marcin Knut ◽  
Rick Tearle ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Human Populations ◽  
Whole Genome ◽  
Linkage Disequilibrium Structure ◽  
Genome Sequences

scholarly journals Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome

2018 ◽  
Vol 92 (12) ◽  
pp. e00017-18 ◽  
Author(s):  
Yusuke Hirose ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Seiichiro Mori ◽  
Yoshiyuki Ishii ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cervical Cancer ◽  
Deep Sequencing ◽  
Viral Genome ◽  
Reference Sequence ◽  
Characteristic Change ◽  
Whole Genome ◽  
Cervical Carcinogenesis ◽  
Genome Sequences ◽  
Host Genetic

ABSTRACTPersistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1,n= 56; CIN2/3,n= 68; ICC,n= 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions.IMPORTANCEHPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.

scholarly journals Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018

2019 ◽  
Vol 24 (10) ◽  
Author(s):  
David W Eyre ◽  
Katy Town ◽  
Teresa Street ◽  
Leanne Barker ◽  
Nicholas Sanderson ◽  
...  
Keyword(s):  
United Kingdom ◽  
Neisseria Gonorrhoeae ◽  
Whole Genome ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Sexual Network ◽  
The United Kingdom ◽  
Intermediate Resistance ◽  
Azithromycin Resistance ◽  
Urgent Action

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

scholarly journals Tracking human population structure through time from whole genome sequences

2019 ◽  
Author(s):  
Ke Wang ◽  
Iain Mathieson ◽  
Jared O’Connell ◽  
Stephan Schiffels
Keyword(s):  
Population Structure ◽  
Gene Flow ◽  
Demographic History ◽  
Time Dependent ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
Migration Model ◽  
Novel Approach ◽  
Different Populations

AbstractThe genetic diversity of humans, like many species, has been shaped by a complex pattern of population separations followed by isolation and subsequent admixture. This pattern, reaching at least as far back as the appearance of our species in the paleontological record, has left its traces in our genomes. Reconstructing a population’s history from these traces is a challenging problem. Here we present a novel approach based on the Multiple Sequentially Markovian Coalescent (MSMC) to analyse the population separation history. Our approach, called MSMC-IM, uses an improved implementation of the MSMC (MSMC2) to estimate coalescence rates within and across pairs of populations, and then fits a continuous Isolation-Migration model to these rates to obtain a time-dependent estimate of gene flow. We show, using simulations, that our method can identify complex demographic scenarios involving post-split admixture or archaic introgression. We apply MSMC-IM to whole genome sequences from 15 worldwide populations, tracking the process of human genetic diversification. We detect traces of extremely deep ancestry between some African populations, with around 1% of ancestry dating to divergences older than a million years ago.Author SummaryHuman demographic history is reflected in specific patterns of shared mutations between the genomes from different populations. Here we aim to unravel this pattern to infer population structure through time with a new approach, called MSMC-IM. Based on estimates of coalescence rates within and across populations, MSMC-IM fits a time-dependent migration model to the pairwise rate of coalescences. We implemented this approach as an extension to existing software (MSMC2), and tested it with simulations exhibiting different histories of admixture and gene flow. We then applied it to the genomes from 15 worldwide populations to reveal their pairwise separation history ranging from a few thousand up to several million years ago. Among other results, we find evidence for remarkably deep population structure in some African population pairs, suggesting that deep ancestry dating to one million years ago and older is still present in human populations in small amounts today.

scholarly journals The Identification of the SARS-CoV-2 Whole Genome: Nine Cases Among Patients in Banten Province, Indonesia

2021 ◽  
Author(s):  
Chris Adhiyanto ◽  
Laifa A. Hendarmin ◽  
Erike A. Suwarsono ◽  
Zeti Harriyati ◽  
Suryani ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Genetic Variants ◽  
Viral Genome ◽  
Genetic Background ◽  
Respiratory Illness ◽  
Whole Genome ◽  
Sequencing Data ◽  
Rt Pcr ◽  
Genome Sequences ◽  
Severe Patient

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the current pandemic. Viral genome sequencing has been widely applied during outbreaks to study the relatedness of this virus to other viruses, its transmission mode, pace, evolution and geographical spread, and also its adaptation to human hosts. To date, more than 90,000 SARS-CoV-2 genome sequences have been uploaded to the GISAID database. The availability of sequencing data along with clinical and geographical data may be useful for epidemiological investigations. In this study, we aimed to analyse the genetic background of SARS-CoV-2 from patients in Indonesia by whole genome sequencing. We examined nine samples from COVID-19 patients with RT-PCR cycle threshold (Ct) of less than 25 using ARTIC Network protocols for Oxford Nanopore’s Gridi On sequencer. The analytical methods were based on the ARTIC multiplex PCR sequencing protocol for COVID-19. In this study, we found that several genetic variants within the nine COVID-19 patient samples. We identified a mutation at position 614 P323L mutation in the ORF1ab gene often found in our severe patient samples. The number of SNPs and their location within the SARS-CoV-2 genome seems to vary. This diversity might be responsible for the virulence of the virus and its clinical manifestation.

scholarly journals Nuclease pre-treatment increases efficiency of whole genome sequencing of Influenza B virus in respiratory specimens

2020 ◽  
pp. 1-13
Author(s):  
Wudtichai Manasatienkij ◽  
Piyawan Chinnawirotpisan ◽  
Weerayuth Kittichotirat ◽  
Sriluck Simasathien ◽  
Louis R. Macareo ◽  
...  
Keyword(s):  
Human Genome ◽  
Viral Genome ◽  
Bacterial Genome ◽  
Whole Genome Sequence ◽  
Influenza B Virus ◽  
Influenza B ◽  
Whole Genome ◽  
Genome Sequences ◽  
B Virus ◽  
Respiratory Specimens

The use of next generation sequencing (NGS) directly on respiratory specimens to obtain viral whole genome sequence (WGS) enhances the capability for rapid and unbiased viral characterization. One of the challenges of using NGS directly in influenza-like illness (ILI) respiratory specimens is the higher proportion of host and bacterial genome compared to viral genetic materials found, which reduces the likelihood of obtaining complete viral genome sequences. This study aims to evaluate nuclease pretreatments prior to sequencing of influenza B virus directly from ILI respiratory specimens. Sequence data were mapped to human, bacteria and influenza B viral genome. In the absence of any nuclease pretreatments, the sequence reads identified as Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria meningitidis and Veillonella parvula were the most prominent genetic materials in respiratory specimens. Filtration followed by nuclease treatment reduced bacterial sequence reads by at least 70 folds in all 4 tested samples, supporting the direct application of NGS in ILI respiratory specimens. Although the pretreatment methods significantly reduced human genome sequences, the remaining human genome especially human rRNA still impact the number and proportion of the viral sequence reads.

scholarly journals De Novo Whole-Genome Sequencing and Annotation of Pathogenic Bovine Pasteurella multocida Type A:3 Strains

2020 ◽  
Vol 9 (49) ◽  
Author(s):  
Morag Livingstone ◽  
Kevin Aitchison ◽  
Mark Dagleish ◽  
David Longbottom
Keyword(s):  
Genome Sequencing ◽  
Pasteurella Multocida ◽  
De Novo ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
Pneumonic Pasteurellosis ◽  
The United Kingdom ◽  
The World ◽  
Welfare Implications

ABSTRACT Pneumonic pasteurellosis, caused by Pasteurella multocida, is a common respiratory infection of ruminants that has major economic and welfare implications throughout the world. Here, we report the annotated genome sequences of seven pathogenic strains of P. multocida that were isolated from cattle in the United Kingdom.

scholarly journals Ultrafast Sample Placement on Existing Trees (UShER) Empowers Real-Time Phylogenetics for the SARS-CoV-2 Pandemic

2020 ◽  
Author(s):  
Yatish Turakhia ◽  
Bryan Thornlow ◽  
Angie S. Hinrichs ◽  
Nicola De Maio ◽  
Landen Gozashti ◽  
...  
Keyword(s):  
Real Time ◽  
Viral Genome ◽  
Genome Browser ◽  
Contact Tracing ◽  
Human Populations ◽  
Genome Sequences ◽  
New Era ◽  
Link Type ◽  
History Of ◽  
Local Transmission

AbstractAs the SARS-CoV-2 virus spreads through human populations, the unprecedented accumulation of viral genome sequences is ushering a new era of “genomic contact tracing” – that is, using viral genome sequences to trace local transmission dynamics. However, because the viral phylogeny is already so large – and will undoubtedly grow many fold – placing new sequences onto the tree has emerged as a barrier to real-time genomic contact tracing. Here, we resolve this challenge by building an efficient, tree-based data structure encoding the inferred evolutionary history of the virus. We demonstrate that our approach improves the speed of phylogenetic placement of new samples and data visualization by orders of magnitude, making it possible to complete the placements under real-time constraints. Our method also provides the key ingredient for maintaining a fully-updated reference phylogeny. We make these tools available to the research community through the UCSC SARS-CoV-2 Genome Browser to enable rapid cross-referencing of information in new virus sequences with an ever-expanding array of molecular and structural biology data. The methods described here will empower research and genomic contact tracing for laboratories worldwide.Software AvailabilityUSHER is available to users through the UCSC Genome Browser at https://genome.ucsc.edu/cgi-bin/hgPhyloPlace. The source code and detailed instructions on how to compile and run UShER are available from https://github.com/yatisht/usher.

scholarly journals Geographic and Phylodynamic Distribution of SARS-CoV-2 from Environmental Origin

2021 ◽  
Author(s):  
Elijah Kolawole Oladipo ◽  
Boluwatife Ayobami Irewolede ◽  
Precious Moyosoluwa Oyewole ◽  
Emmanuel Oluwatobi Dairo ◽  
Ayodele Eugene Ayeni ◽  
...  
Keyword(s):  
United States ◽  
Severe Acute Respiratory Syndrome ◽  
Common Ancestor ◽  
Evolutionary Process ◽  
Geographic Location ◽  
The United States ◽  
Transmission Dynamics ◽  
Whole Genome ◽  
Genome Sequences ◽  
Phylodynamic Analysis

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Understanding the transmission dynamics of SARS-CoV-2 contamination in the environment is essential for infection control policies. This study aims to provide a phylodynamic analysis and distribution pattern of SARS-CoV-2 from the environment in terms of Source, clades, lineages, and their location. Ninety (90) retrieved whole-genome sequences of environmental sources from GISAID were investigated to determine the evolutionary process of SARS-CoV-2 and mutation in the isolated nucleotide sequences. The analysis was carried out using R, MAFFT, and MEGA X software. Out of the five countries studied, Austria has the highest distribution with sixty-five samples (72.2%), and the highest isolates of 68 (75.6%) were from raw sewage. The highest clade in circulation as obtained from the study is G with lineages B. The phylogeny of SARS-CoV-2 whole-genome sequences from Austria, the United States, China, Brazil, and Liechtenstein indicated that the SARS-CoV-2 viruses were all clustered together, irrespective of sequence geographic location. The study concluded by demonstrating a clear interconnection between the phylogeny of SARS-CoV-2 isolates from various geographic locations, all of which were locked in the same cluster regardless of their environment specimen. Thus, depicting the possibility of their origination from a common ancestor.

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