scholarly journals Emergence of Novel SARS-CoV-2 Variants in the Netherlands

2020 ◽  
Author(s):  
Aysun Urhan ◽  
Thomas Abeel
Keyword(s):  
Genetic Diversity ◽  
The Netherlands ◽  
Vaccine Development ◽  
Genomic Variation ◽  
Reference Sequence ◽  
Viral Population ◽  
Whole Genome ◽  
Local Dynamics ◽  
Novel Variants ◽  
N Proteins

AbstractIn this study, we analyzed SARS-CoV-2 genomes in the Netherlands, in the context of global viral population since the beginning of the pandemic. We have identified the most variant sites on the whole genome as well as the stable, conserved ones on the S and N proteins. We found four mutations, S:D614G, NSP12b:P314L, NSP3:F106F, to be the most frequent ones that dominate the SARS-CoV-2 population outside of China. We detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters, indicating community spread. We emphasize that while SARS-CoV-2 is evolving, and the number of mutations from the reference sequence is increasing, we observe only little diversity in the new variants as we enter the later stages of the pandemic. Our analyses suggest we have diverged away from the current SARS-CoV-2 reference enough that the reference should be re-evaluated to represent the current viral population more accurately. We assert our work provides valuable information on the genetic diversity of SARS-CoV-2 and its local dynamics in the Netherlands, especially for DNA-based diagnostic, therapeutic or vaccine development against COVID-19. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed.

scholarly journals Emergence of novel SARS-CoV-2 variants in the Netherlands

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aysun Urhan ◽  
Thomas Abeel
Keyword(s):  
The Netherlands ◽  
Population Diversity ◽  
Genomic Variation ◽  
Population Variation ◽  
Reference Sequence ◽  
Viral Population ◽  
Phylogenetic Study ◽  
First Case ◽  
Novel Variants ◽  
Frequent Mutations

AbstractCoronavirus disease 2019 (COVID-19) has emerged in December 2019 when the first case was reported in Wuhan, China and turned into a pandemic with 27 million (September 9th) cases. Currently, there are over 95,000 complete genome sequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, in public databases, accompanying a growing number of studies. Nevertheless, there is still much to learn about the viral population variation when the virus is evolving as it continues to spread. We have analyzed SARS-CoV-2 genomes to identify the most variant sites, as well as the stable, conserved ones in samples collected in the Netherlands until June 2020. We identified the most frequent mutations in different geographies. We also performed a phylogenetic study focused on the Netherlands to detect novel variants emerging in the late stages of the pandemic and forming local clusters. We investigated the S and N proteins on SARS-CoV-2 genomes in the Netherlands and found the most variant and stable sites to guide development of diagnostics assays and vaccines. We observed that while the SARS-CoV-2 genome has accumulated mutations, diverging from reference sequence, the variation landscape is dominated by four mutations globally, suggesting the current reference does not represent the virus samples circulating currently. In addition, we detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters and region-specific sub-populations indicating community spread. We explored SARS-CoV-2 variants in the Netherlands until June 2020 within a global context; our results provide insight into the viral population diversity for localized efforts in tracking the transmission of COVID-19, as well as sequenced-based approaches in diagnostics and therapeutics. We emphasize that little diversity is observed globally in recent samples despite the increased number of mutations relative to the established reference sequence. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed to speed up diagnostics and vaccine design.

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 Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

2020 ◽  
Author(s):  
Jerome R Lon ◽  
Yunmeng Bai ◽  
Bingxu Zhong ◽  
Fuqaing Cai ◽  
Hongli Du
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Surface Protein ◽  
The Other ◽  
Reference Sequence ◽  
Prediction Methods ◽  
Whole Genome ◽  
B Cell Epitopes ◽  
Conformational Epitopes ◽  
Linear Epitopes

AbstractThe discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed. 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study. The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

scholarly journals SARS-CoV-2 whole-genome classification analysis, protein homology modelling and elucidation of associated protein functions

2020 ◽  
Author(s):  
Deepanshu Sharma ◽  
Anamika Saini ◽  
Desh Deepak Singh
Keyword(s):  
Vaccine Development ◽  
Homology Modelling ◽  
Protein Structures ◽  
Whole Genome Sequence ◽  
Reference Sequence ◽  
Sequence Length ◽  
Whole Genome ◽  
Protein Homology ◽  
Whole Genome Analysis ◽  
Multiple Sequence

The most recent whole-genome sequence of SARS-CoV-2 was published on NCBI on 13th March 2020, with accession no. NC_045512. The protein products, genetic features, sequence length, NCBI reference sequence, protein structures (published/ homology modelling) and functions are discussed and analysed in this paper. Multiple sequence alignment is performed and Phylogenic tree is prepared for the 4 closely related coronavirus species. This study provides the whole genome analysis with protein homology structures and elucidates functions of structurally similar proteins for further exploration and contributes to the search for anti-SARS-CoV-2 drugs. The application of this data in new vaccine development techniques such as Rapid-Response Platform and a possibility of a recombinant SARS-CoV-2 are discussed in this paper.

scholarly journals Population genetic analysis of Indian SARS-CoV-2 isolates reveals a unique phylogenetic cluster

2020 ◽  
Author(s):  
Dhruv Das ◽  
V.S.S.N.R Akkipeddi
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analysis ◽  
Genetic Polymorphism ◽  
Population Genetic ◽  
Vaccine Development ◽  
Viral Population ◽  
Population Genetic Analysis ◽  
Phylogenetic Cluster ◽  
Indian Study ◽  
Novel Virus

AbstractThe SARS-CoV-2 pandemic originated from Wuhan, China in December 2019 raised an alarming situation all over the globe. Sequencing of this novel virus provides an opportunity to evaluate the genetic polymorphism present in the viral population. Herein, we analysed 173 sequences isolated from Indian patients and performed SNP linkage, clustering and phylogenetic analysis to understand the local genetic diversity. We found that the SNP linkages that lead to the identification of some global clades, do not hold true for the local clade classification. In addition to the unique cluster, established by another Indian study, we identified a new cluster (I-20D) that encompasses 28% of the analysed sequences. This cluster is defined by two linked variations – C22444T and C28854T. A detailed study of such polymorphisms can be useful for drug and vaccine development.

scholarly journals Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

2020 ◽  
Author(s):  
Jerome Rumdon Lon ◽  
Yunmeng Bai ◽  
Bingxu Zhong ◽  
Fuqaing Cai ◽  
Hongli Du
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Surface Protein ◽  
The Other ◽  
Reference Sequence ◽  
Prediction Methods ◽  
Whole Genome ◽  
B Cell Epitopes ◽  
Conformational Epitopes ◽  
Linear Epitopes

Abstract Background The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine.Methods The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed.Results 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study.Conclusion The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

scholarly journals Assessing genomic diversity and signatures of selection in Jiaxian Red cattle using whole-genome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoting Xia ◽  
Shunjin Zhang ◽  
Huaju Zhang ◽  
Zijing Zhang ◽  
Ningbo Chen ◽  
...  
Keyword(s):  
Population Structure ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
System Response ◽  
Whole Genome ◽  
Population Structure Analysis ◽  
Native Cattle ◽  
Genomic Regions

Abstract Background Native cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. Jiaxian Red, a Chinese native cattle breed, is reported to have originated from crossbreeding between taurine and indicine cattle; their history as a draft and meat animal dates back at least 30 years. Using whole-genome sequencing (WGS) data of 30 animals from the core breeding farm, we investigated the genetic diversity, population structure and genomic regions under selection of Jiaxian Red cattle. Furthermore, we used 131 published genomes of world-wide cattle to characterize the genomic variation of Jiaxian Red cattle. Results The population structure analysis revealed that Jiaxian Red cattle harboured the ancestry with East Asian taurine (0.493), Chinese indicine (0.379), European taurine (0.095) and Indian indicine (0.033). Three methods (nucleotide diversity, linkage disequilibrium decay and runs of homozygosity) implied the relatively high genomic diversity in Jiaxian Red cattle. We used θπ, CLR, FST and XP-EHH methods to look for the candidate signatures of positive selection in Jiaxian Red cattle. A total number of 171 (θπ and CLR) and 17 (FST and XP-EHH) shared genes were identified using different detection strategies. Functional annotation analysis revealed that these genes are potentially responsible for growth and feed efficiency (CCSER1), meat quality traits (ROCK2, PPP1R12A, CYB5R4, EYA3, PHACTR1), fertility (RFX4, SRD5A2) and immune system response (SLAMF1, CD84 and SLAMF6). Conclusion We provide a comprehensive overview of sequence variations in Jiaxian Red cattle genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Jiaxian Red cattle. We observed a high level of genomic diversity and low inbreeding in Jiaxian Red cattle. These results provide a basis for further resource protection and breeding improvement of this breed.

scholarly journals Clinical-grade whole-genome sequencing and 3′ transcriptome analysis of colorectal cancer patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Agata Stodolna ◽  
Miao He ◽  
Mahesh Vasipalli ◽  
Zoya Kingsbury ◽  
Jennifer Becq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Transcriptome Analysis ◽  
Variant Calling ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Whole Genome ◽  
Clinical Grade ◽  
Pathway Gene

Abstract Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of > 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

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