scholarly journals The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Black Queen rule

2022 ◽  
Author(s):  
Philippe Colson ◽  
philippe Gautret ◽  
Jeremy Delerce ◽  
Herve Chaudet ◽  
Pierre Pontarotti ◽  
...  
Keyword(s):  
Growth Rate ◽  
Next Generation Sequencing ◽  
Stop Codon ◽  
Rna Virus ◽  
The Other ◽  
Average Lifetime ◽  
Death Rates ◽  
Alpha Variant ◽  
Kinetics Of ◽  
Generation Sequencing

The nature and dynamics of mutations associated with the emergence, spread and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (Marseille-4) for 10 months since its onset in July 2020. Here, we analysed and classified into subvariants and lineages 7,453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1+/-1.4 months, during which 4.1+/-2.6 mutations accumulated. Growth rate was 0.079+/-0.045, varying from 0.010 to 0.173. All the lineages exhibited a gamma distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in several mink lineages and in the alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.

scholarly journals Clinical and Genetic Spectrum of Stargardt Disease in Argentinean Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcela D. Mena ◽  
Angélica A. Moresco ◽  
Sofía H. Vidal ◽  
Diana Aguilar-Cortes ◽  
María G. Obregon ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Next Generation Sequencing ◽  
Final Analysis ◽  
The Other ◽  
South American ◽  
Stargardt Disease ◽  
Targeted Next Generation Sequencing ◽  
Mutational Spectrum ◽  
Genetic Features ◽  
Generation Sequencing

PurposeTo describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients.MethodsThis retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients.ResultsWe found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes.ConclusionThis study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.

scholarly journals A Retrospective Paired Comparison Between Untargeted Next Generation Sequencing and Conventional Microbiology Tests With Wisely Chosen Metagenomic Sequencing Positive Criteria

2021 ◽  
Vol 8 ◽  
Author(s):  
Hanyu Qin ◽  
Jinmin Peng ◽  
Ling Liu ◽  
Jing Wu ◽  
Lingai Pan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Fungal Infections ◽  
Rna Virus ◽  
Paired Comparison ◽  
Final Analysis ◽  
Metagenomic Sequencing ◽  
Next Generation ◽  
Dna Virus ◽  
Virus Identification ◽  
Generation Sequencing

Objectives: To evaluate the performance of metagenomic next generation sequencing (mNGS) using adequate criteria for the detection of pathogens in lower respiratory tract (LRT) samples with a paired comparison to conventional microbiology tests (CMT).Methods: One hundred sixty-seven patients were reviewed from four different intensive care units (ICUs) in mainland China during 2018 with both mNGS and CMT results of LRT samples available. The reads per million ratio (RPMsample/RPMnon−template−control ratio) and standardized strictly mapped reads number (SDSMRN) were the two criteria chosen for identifying positive pathogens reported from mNGS. A McNemar test was used for a paired comparison analysis between mNGS and CMT.Results: One hundred forty-nine cases were counted into the final analysis. The RPMsample/RPMNTC ratio criterion performed better with a higher accuracy for bacteria, fungi, and virus than SDSMRN criterion [bacteria (RPMsample/RPMNTC ratio vs. SDSMRN), 65.1 vs. 55.7%; fungi, 75.8 vs. 71.1%; DNA virus, 86.3 vs. 74.5%; RNA virus, 90.9 vs. 81.8%]. The mNGS was also superior in bacteria detection only if an SDSMRN ≥3 was used as a positive criterion with a paired comparison to culture [SDSMRN positive, 92/149 (61.7%); culture positive, 54/149 (36.2%); p < 0.001]; however, it was outperformed with significantly more fungi and DNA virus identification when choosing both criteria for positive outliers [fungi (RPMsample/RPMNTC ratio vs. SDSMRN vs. culture), 23.5 vs. 29.5 vs. 8.7%, p < 0.001; DNA virus (RPMsample/RPMNTC ratio vs. SDSMRN vs. PCR), 14.1 vs. 20.8 vs. 11.8%, p < 0.05].Conclusions: Metagenomic next generation sequencing may contribute to revealing the LRT infection etiology in hospitalized groups of potential fungal infections and in situations with less access to the multiplex PCR of LRT samples from the laboratory by choosing a wise criterion like the RPMsample/RPMNTC ratio.

scholarly journals A beginner’s guide for FMDV quasispecies analysis: sub-consensus variant detection and haplotype reconstruction using next-generation sequencing

2019 ◽  
Vol 21 (5) ◽  
pp. 1766-1775 ◽  
Author(s):  
Marco Cacciabue ◽  
Anabella Currá ◽  
Elisa Carrillo ◽  
Guido König ◽  
María Inés Gismondi
Keyword(s):  
Next Generation Sequencing ◽  
Rna Virus ◽  
Foot And Mouth Disease ◽  
Next Generation Sequencing Data ◽  
Complete Analysis ◽  
Viral Quasispecies ◽  
Next Generation ◽  
Sequencing Data ◽  
Viral Genomes ◽  
Generation Sequencing

Abstract Deep sequencing of viral genomes is a powerful tool to study RNA virus complexity. However, the analysis of next-generation sequencing data might be challenging for researchers who have never approached the study of viral quasispecies by this methodology. In this work we present a suitable and affordable guide to explore the sub-consensus variability and to reconstruct viral quasispecies from Illumina sequencing data. The guide includes a complete analysis pipeline along with user-friendly descriptions of software and file formats. In addition, we assessed the feasibility of the workflow proposed by analyzing a set of foot-and-mouth disease viruses (FMDV) with different degrees of variability. This guide introduces the analysis of quasispecies of FMDV and other viruses through this kind of approach.

Growth Kinetics Of SiO2 On (001)Si Catalyzed By Cu3Si At Elevated Temperatures

1999 ◽  
Vol 564 ◽  
Author(s):  
H. Y. Huang ◽  
L. J. Chen
Keyword(s):  
Growth Rate ◽  
Growth Kinetics ◽  
Electron Spectroscopy ◽  
Auger Electron ◽  
Linear Growth ◽  
Elevated Temperatures ◽  
The Other ◽  
Wet Oxidation ◽  
Transmission Electron ◽  
Kinetics Of

AbstractThe oxidation of Si catalyzed by 170-nm-thick Cu3Si at elevated temperatures has been investigated by transmission electron microscopy and Auger electron spectroscopy. For wet oxidation at 140–180 °C, the growth rate of the oxide layer was increased with the temperature. On the other hand, as the temperature was increased above 200 °C, the growth rate slowed down. The growth kinetics of oxide was investigated. Controlling mechanisms for the growth of oxide owing to the grain growth of Cu3Si are discussed. The activation energy for the linear growth of oxide was measured to be 0. 19 ± 0.1 eV.

A novel homozygous frameshift mutation in the FUCA1 gene causes both severe and mild fucosidosis

2018 ◽  
Vol 71 (9) ◽  
pp. 821-824 ◽  
Author(s):  
Nasrollah Saleh-Gohari ◽  
Kolsoum Saeidi ◽  
Roya Zeighaminejad
Keyword(s):  
Next Generation Sequencing ◽  
Frameshift Mutation ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Gene Mutations ◽  
Next Generation ◽  
Lysosomal Storage ◽  
Illumina Hiseq ◽  
Almost All ◽  
Generation Sequencing

AimsFucosidosis is a rare autosomal recessive lysosomal storage disorder caused by α-L-fucosidase deficiency as a result of FUCA1 gene mutations. Here, we studied clinical features and the molecular basis of fucosidosis in a family from Iran, including two probands and nine family members.MethodsDNA sample of two probands were screened for gene defects using a next generation sequencing technique. The sequencing processes were performed on an Illumina Hiseq 4000 platform. Sequence reads were analysed using BWA-GATK.ResultsNext generation sequencing revealed a frameshift mutation caused by 2 bp deletion (c.837_838 delTG; p.Cys279) in the FUCA1 gene. The identified mutation was tested in all participants. Homozygous patients had almost all the complications associated with fucosidosis, while heterozygous carriers were unaffected.ConclusionsThe variant c.837_838 delTG; p.Cys279 has not been reported previously and is predicted to be pathogenic due to a premature stop codon.

scholarly journals Identification of a Novel SARS-CoV-2 Strain with Truncated Protein in ORF8 Gene by Next Generation Sequencing

2021 ◽  
Author(s):  
Stephanie DeRonde ◽  
Hannah Deuling ◽  
Jayme Parker ◽  
Jack Chen
Keyword(s):  
Next Generation Sequencing ◽  
Stop Codon ◽  
Washington State ◽  
The Novel ◽  
Next Generation ◽  
Sequencing Technology ◽  
Truncated Protein ◽  
Next Generation Sequencing Technology ◽  
Protein Mutation ◽  
Generation Sequencing

Abstract Using next generation sequencing technology, we identified a truncated protein mutation located in the ORF8 gene which is near the end of the genome from nucleotides 27,878 to 27,958. The mutation in this novel strain created a stop codon and translates to the novel truncated ORF8 protein, creating a much smaller protein than most other strains of SARS-CoV-2. The novel truncated mutation is most closely related to nine SARS-CoV-2 strains found in Washington state. Our results show a novel strain of SARS-CoV-2 with a truncated ORF8 gene. This shortens the translated ORF8 protein. The effects of ORF8 protein and its functions are still uncertain but a truncated ORF8 could affect antibody response, severity of infection and inflammatory response.

An investigation into the impact of next generation sequencing on the use of targeted treatments in glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2035-2035
Author(s):  
Jordan John ◽  
Rimas Vincas Lukas ◽  
Priya Kumthekar
Keyword(s):  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Treatment Decisions ◽  
The Other ◽  
Targeted Treatment ◽  
Additional Patient ◽  
Next Generation ◽  
The Impact ◽  
Generation Sequencing ◽  
Gene Alterations

2035 Background: Next-generation sequencing (NGS) provides clinicians immense amounts of information about a patient’s cancer. NGS allows the detection of a wide range of gene alterations undetectable by older techniques. This has the promise to help guide clinicians in their decision-making as genetic alterations can be both prognostic and predictive. NGS may reveal new treatment options for patients with glioblastoma. The goal of this project was to evaluate how often NGS results influence the use of targeted treatment agents in glioblastoma. This study did not investigate the impact of NGS on reclassification of cancers, prognosis, or treatment decisions outside of the use of targeted therapy. Methods: We conducted a retrospective chart review to see if adult glioblastoma patients received treatments for potentially actionable gene alterations and for fusion variants because of NGS. Here we looked at alterations labeled as actionable from the Tempus company’s NGS results. We collected diagnosis and treatment information from the Electronic Medical Record and from the Electronic Data Warehouse. We examined if patients after receiving NGS would receive targeted treatment, as that likely indicated these treatments were given due to NGS indication. We excluded cytotoxic chemotherapy agents and bevacizumab as these therapies are utilized regardless of a targeted gene indication. This analysis excluded treatments received in clinical trials in which enrollment was independent of NGS. This analysis looked at the proportion of patients with actionable alterations that were treated with targeted agents. Results: 261 glioblastoma patients were found on NGS to have mutations which were potentially actionable. Thirty-three of these patients (12.6%) received a respective targeted therapy, and the other 228 patients (87.4%) did not receive an NGS guided targeted therapy. 97 patients had EGFR copy number gains or EGFR gain of function mutations of which 21 were treated with depatuxizumab mafodotin, and one additional patient who was treated with ABBV 321. Of the NGS treatment guided therapies, depatuxizumab mafodotin was the most used targeted agent in our sample set. Additionally, there were 30 patients with fusion variants and 11 of them were FGFR3-TACC3 fusions. Of these 11, 4 received targeted regimens (36.4%) with either TAS-120, pemigatinib, erdafitinib, or erdafitinib with ponatinib. The other fusion variants were not acted upon. Conclusions: These preliminary results suggest that NGS data currently does not frequently impact treatment decisions for glioblastoma. Although this study is limited by being a single institution study, future efforts include expanding this analysis to multiple institutions. With improvements in therapeutics as well as with wider availability of NGS testing, sequencing data may impact a larger percentage of glioblastoma patients.

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