scholarly journals Quality control of low-frequency variants in SARS-CoV-2 genomes

2020 ◽  
Author(s):  
Mikhail Rayko ◽  
Aleksey Komissarov
Keyword(s):  
Quality Control ◽  
Mutation Rate ◽  
Low Frequency ◽  
Comprehensive Analysis ◽  
Tree Topology ◽  
Viral Mutation ◽  
Variant Frequency ◽  
Current Outbreak ◽  
Lower Transition

AbstractDuring the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.

scholarly journals Responding kinetic of B-cell receptor repertoire to the Toll-like receptor 7/8 stimulation in non-human primates

2021 ◽  
Author(s):  
Shiyu Wang ◽  
Judith Mandl ◽  
Mark Feinberg ◽  
Michael Citron ◽  
Nitin K. Saksena ◽  
...  
Keyword(s):  
B Cell ◽  
Mutation Rate ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Low Frequency ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Repertoire ◽  
Cell Immunity ◽  
Repertoire Diversity

TLR7 and 8 regulate B cell immunity, but the precise details of the mechanism are still unclear. Here, we studied the kinetics of both heavy and light chains (IgKL) of B-cell receptor (BCR) repertoire responding to the TLR7/8 stimulation in two geniuses of non-human primates (NHPs), African green monkeys (AGMs) and rhesus macaques (RMs). We evaluated the activation of lymphocytes by flow cytometry and studied characteristics of BCR repertoire in terms of gene usage, repertoire diversity, and the number of lineages. Although AGMs had a weaker activation than RMs, and a different responding kinetic, both AGMs and RMs presented an increased IgKL repertoire diversity and lineages expansion. It suggested that the responding time rather than initiation of TLR7/8-induced IgKL repertoire response related to B cell activation. Expanded IgKL lineages with frequency from 0.001% to 1% had an elevated mutation rate and expanded IgH lineages used more IgA/G/E, suggesting that the TLR7/8 stimulation expanded low-frequent but high-mutated lineages. Besides, most of expanded IgKL lineages were lambda isotype. In conclusion, TLR7/8 selectively expands IgKL lineages with a high mutation rate, low frequency, and lambda isotype. The selective effect of TLR7/8 on BCR repertoire allows TLR7/8 agonists to be adjuvant for selectively accelerating antibody maturation.

scholarly journals Viral Mutation Rates

2010 ◽  
Vol 84 (19) ◽  
pp. 9733-9748 ◽  
Author(s):  
Rafael Sanjuán ◽  
Miguel R. Nebot ◽  
Nicola Chirico ◽  
Louis M. Mansky ◽  
Robert Belshaw
Keyword(s):  
Mutation Rate ◽  
Rna Viruses ◽  
Experimental Testing ◽  
Mutation Rates ◽  
Cell Infection ◽  
Nucleotide Substitutions ◽  
Data Set ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Viral Mutation

ABSTRACT Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10−8 to10−6 s/n/c for DNA viruses and from 10−6 to 10−4 s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut .

scholarly journals Detection of genomic alterations in breast cancer with circulating tumour DNA sequencing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dimitrios Kleftogiannis ◽  
Danliang Ho ◽  
Jun Xian Liew ◽  
Polly S. Y. Poon ◽  
Anna Gan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Low Frequency ◽  
Copy Number Variations ◽  
Plasma Dna ◽  
Bioinformatics Pipeline ◽  
Genomic Alterations ◽  
Target Region ◽  
Variant Frequency ◽  
Circulating Tumour Dna ◽  
Reference Samples

Abstract Analysis of circulating cell-free DNA (cfDNA) has opened new opportunities for characterizing tumour mutational landscapes with many applications in genomic-driven oncology. We developed a customized targeted cfDNA sequencing approach for breast cancer (BC) using unique molecular identifiers (UMIs) for error correction. Our assay, spanning a 284.5 kb target region, is combined with a novel freely-licensed bioinformatics pipeline that provides detection of low-frequency variants, and reliable identification of copy number variations (CNVs) directly from plasma DNA. We first evaluated our pipeline on reference samples. Then in a cohort of 35 BC patients our approach detected actionable driver and clonal variants at low variant frequency levels in cfDNA that were concordant (77%) with sequencing of primary and/or metastatic solid tumour sites. We also detected ERRB2 gene CNVs used for HER2 subtype classification with 80% precision compared to immunohistochemistry. Further, we evaluated fragmentation profiles of cfDNA in BC and observed distinct differences compared to data from healthy individuals. Our results show that the developed assay addresses the majority of tumour associated aberrations directly from plasma DNA, and thus may be used to elucidate genomic alterations in liquid biopsy studies.

scholarly journals Optimal number of spacers in CRISPR arrays

2017 ◽  
Author(s):  
Alexander Martynov ◽  
Konstantin Severinov ◽  
Yaroslav Ispolatov
Keyword(s):  
Adaptive Immunity ◽  
Mutation Rate ◽  
Bacterial Genome ◽  
Molecular Machines ◽  
Optimal Number ◽  
Evolutionary Models ◽  
Bacterial Survival ◽  
Crispr Array ◽  
Viral Mutation ◽  
Huge Variety

AbstractWe estimate the number of spacers in a CRISPR array of a bacterium which maximizes its protection against a viral attack. The optimality follows from a competition between two trends: too few distinct spacers make the bacteria vulnerable to an attack by a virus with mutated corresponding protospacers, while an excessive variety of spacers dilutes the number of the CRISPR complexes armed with the most recent and thus most effective spacers. We first evaluate the optimal number of spacers in a simple scenario of an infection by a single viral species and later consider a more general case of multiple viral species. We find that depending on such parameters as the concentration of CRISPR-CAS interference complexes and its preference to arm with more recently acquired spacers, the rate of viral mutation, and the number of viral species, the predicted optimal array length lies within a range quite reasonable from the viewpoint of recent experiments.Author summaryCRISPR-Cas system is an adaptive immunity defense in bacteria and archaea against viruses. It works by accumulating in bacterial genome an array of spacers, or fragments of virus DNA from previous attacks. By matching spacers to corresponding parts of virus DNA called protospacers, CRISPR-Cas system identifies and destroys intruder DNA. Here we theoretically estimate the number of spacers that maximizes bacterial survival. This optimum emerges from a competition between two trends: More spacers allow a bacterium to hedge against mutations in viral protospacers. However, keeping too many spacers makes the older ones inefficient because of accumulation of mutations in corresponding protospacers in viruses. Thus, fewer CRISPR-Cas molecular machines are left armed with more efficient young spacers. We have shown that a higher efficiency of CRISPR-Cas system allows a bacterium to utilize more spacers, increasing the optimal array length. On contrary, a higher viral mutation rate makes older spacers useless and favors shorter arrays. A higher diversity in viral species reduces the efficiency of CRISPR-Cas but does not necessary lead to longer arrays. We think that our study provides a new viewpoint at a huge variety in the observed array lengths and adds relevance to evolutionary models of bacterial-phage coexistence.

Comprehensive Analysis of Low-frequency Noise Variability Components in Bulk and FDSOI (SOTB) MOSFETs

2017 ◽  
Author(s):  
K. Maekawa ◽  
H. Makiyama ◽  
Y. Yamamoto ◽  
T. Hasegawa ◽  
S. Okanishi ◽  
...  
Keyword(s):  
Low Frequency ◽  
Comprehensive Analysis ◽  
Frequency Noise ◽  
Low Frequency Noise

Quality control of extended low-frequency sweeps with conventional vibrators

2013 ◽  
Author(s):  
Wei Guowei ◽  
Yang Jinglei ◽  
Jin Yong ◽  
Cui Kai ◽  
Bi Guangming
Keyword(s):  
Quality Control ◽  
Low Frequency ◽  
Frequency Sweeps

A Line Fault Analysis Algorithm Based on the TDR Test Algorithm

2014 ◽  
Vol 686 ◽  
pp. 371-376
Author(s):  
Hai Ye Qiao ◽  
Guang Ling Liang
Keyword(s):  
Fault Location ◽  
Low Frequency ◽  
Comprehensive Analysis ◽  
Fault Analysis ◽  
Analysis Algorithm ◽  
Fault Type ◽  
Time Period ◽  
Test Circuit ◽  
Test Algorithm ◽  
Communication Lines

The use of TDR for a single test to analyze the state of communication lines is not accurate to fault location, It also can cause the confusion of fault type and other drawbacks. This paper proposes a analysis algorithm. It can comprehensive analysis TDR test circuit fault pattern and low-frequency circuit parameters of tested line, then it determines the type and position of faults. During a time period, It tests the circuit impedance with 5-element DC model, records the values of line impedance at different times. Combining Curves of the line impedance and TDR waveforms, It accurately determines fault type of the line through the TDR test and Position of fault. By the trying It can increase the accuracy of judging failure , reduce time of repairing.

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