scholarly journals Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

2021 ◽  
Author(s):  
Andrew L. Valesano ◽  
Kalee E. Rumfelt ◽  
Derek E. Dimcheff ◽  
Christopher N. Blair ◽  
William J. Fitzsimmons ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Temporal Dynamics ◽  
Medical Center ◽  
Variant Calling ◽  
Global Consensus ◽  
Temporal Aspects ◽  
Host Genetic ◽  
Insight Into ◽  
High Depth ◽  
Shared Variation

AbstractAnalysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified a viral load threshold that minimizes false positives. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.

scholarly journals Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

2021 ◽  
Vol 17 (4) ◽  
pp. e1009499
Author(s):  
Andrew L. Valesano ◽  
Kalee E. Rumfelt ◽  
Derek E. Dimcheff ◽  
Christopher N. Blair ◽  
William J. Fitzsimmons ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Medical Center ◽  
Variant Calling ◽  
Critical Factor ◽  
Global Consensus ◽  
Temporal Aspects ◽  
Host Genetic ◽  
Insight Into ◽  
High Depth ◽  
Variant Identification

Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified viral load as a critical factor in variant identification. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.

scholarly journals Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1026 ◽  
Author(s):  
Jiaxin Ling ◽  
Rachel A. Hickman ◽  
Jinlin Li ◽  
Xi Lu ◽  
Johanna F. Lindahl ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Temporal Dynamics ◽  
Evolutionary Rate ◽  
Viral Pathogenesis ◽  
Bayesian Phylogenetic Analysis ◽  
Community Transmission ◽  
Spatio Temporal ◽  
Insight Into ◽  
Over Time

Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites ≥5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 × 10−3 substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches.

scholarly journals DEEPGENTM—A Novel Variant Calling Assay for Low Frequency Variants

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 507
Author(s):  
Bernd Timo Hermann ◽  
Sebastian Pfeil ◽  
Nicole Groenke ◽  
Samuel Schaible ◽  
Robert Kunze ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Genetic Variants ◽  
Liquid Biopsy ◽  
Hot Spot ◽  
Treatment Success ◽  
Low Frequency ◽  
Variant Calling ◽  
Subsequent Treatment ◽  
Precision Oncology ◽  
Orthogonal Comparison

Detection of genetic variants in clinically relevant genomic hot-spot regions has become a promising application of next-generation sequencing technology in precision oncology. Effective personalized diagnostics requires the detection of variants with often very low frequencies. This can be achieved by targeted, short-read sequencing that provides high sequencing depths. However, rare genetic variants can contain crucial information for early cancer detection and subsequent treatment success, an inevitable level of background noise usually limits the accuracy of low frequency variant calling assays. To address this challenge, we developed DEEPGENTM, a variant calling assay intended for the detection of low frequency variants within liquid biopsy samples. We processed reference samples with validated mutations of known frequencies (0%–0.5%) to determine DEEPGENTM’s performance and minimal input requirements. Our findings confirm DEEPGENTM’s effectiveness in discriminating between signal and noise down to 0.09% variant allele frequency and an LOD(90) at 0.18%. A superior sensitivity was also confirmed by orthogonal comparison to a commercially available liquid biopsy-based assay for cancer detection.

scholarly journals scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gavin W. Wilson ◽  
Mathieu Derouet ◽  
Gail E. Darling ◽  
Jonathan C. Yeung
Keyword(s):  
Genetic Variants ◽  
False Positive ◽  
Variant Calling ◽  
Call Rate ◽  
Rna Seq ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Variant Call ◽  
Two Samples ◽  
Co Detection

AbstractIdentifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to “collapse” molecular duplicates and accurately identify variants and their co-expression. We demonstrate that scSNV is fast, with a reduced false-positive variant call rate, and enables the co-detection of genetic variants and A>G RNA edits across twenty-two samples.

scholarly journals AB1010 CLINICAL SPECTRUM AND IMMUNE ANALYSIS OF PATIENTS WITH CRYOPYRIN-ASSOCIATED AUTOINFLAMMATORY SYNDROME IN TAIWAN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1798.1-1798
Author(s):  
C. Y. Wu ◽  
P. S. Chu ◽  
H. Y. Yang
Keyword(s):  
Genetic Variants ◽  
Medical Center ◽  
Laboratory Data ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Medical Intervention ◽  
Stimulation Test ◽  
Autoinflammatory Diseases ◽  
Missense Mutations ◽  
Autoinflammatory Syndrome ◽  
Nlrp3 Gene

Background:Cryopyrin-associated periodic syndromes (CAPS) are emerging autoinflammatory diseases with available treatment. No reports have yet been reported from Taiwan.Objectives:We reviewed cases suspected with CAPS to identify its existence in Taiwan.Methods:Genomic DNA from one hundred and ten cases with symptom signs suggestive of CAPS(1) between 2016-2019 were sent for NLRP3 gene analysis. Clinical presentations, laboratory data, treatment regimens, as well as inflammasome activities were analyzed among those treated in a tertiary medical center in northern Taiwan.Results:Among the 110 cases sequenced, 16 of them were found to carry missense mutations within the NLRP3 gene. Fourteen cases harbored known pathogenic genetic variants (c.1316C>T; c.1574A>T; and c.907G>C) and two carried novel NLRP3 missense mutations (c.210G>A, c.1371G>T)(2) with unknown pathophysiological roles. Through chart review, chronic urticarial, systemic juvenile idiopathic arthritis, Behcet’s disease and refractory Kawasaki disease were most likely diagnosed before genetic analysis were arranged. As compared to chronic infantile neurological, cutaneous and articular syndrome (CINCA) and Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) was the most frequently observed clinical presentation. Plasma serumamyloidA (SAA) and IL-1b were both significantly elevated among the cases diagnosed with CAPS as compared to the controls (p<0.05). IL-18, on the other hand, showed no significant differences between the groups. While the presence of LPS without ATP significantly increased the level of IL-1b in the PBMC stimulation test, IL-18 were significantly elevated in the confirmed CAPS with or without ATP upon LPS stimulation (all p<0.05). Caspase 1 activity were also tested positive among the cases with CAPS. Furthermore, we compared the immune profiles between those CAPS cases harboring pathogenic mutations with the 2 harboring unreported NLRP3 missense mutations and discovered that the PBMC stimulation test in cases with c.210G>A and c.1371G>T mutation did not differ from the healthy controls.Conclusion:The number of NLRP3 gene alterations among patients suspected with CAPS in Taiwan is not low. In order to identify potential patients for proper medical intervention in the future, physician awareness, genetic testing as well as functional analysis are important.References:[1]Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942-7.[2]Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018;55(8):530-7Disclosure of Interests:Chao-Yi Wu Speakers bureau: Abbvie, Boehringer Ingelheim International GmbH, Nestle, Pi-Shuang Chu: None declared, Huang-Yu Yang: None declared

Permutation Min-Entropy and Statistical Complexity Analysis of Electricity Spot Price

2015 ◽  
Vol 14 (04) ◽  
pp. 1550040 ◽  
Author(s):  
Qingju Fan ◽  
Dan Li
Keyword(s):  
Temporal Dynamics ◽  
Complexity Analysis ◽  
Spot Price ◽  
Temporal Correlations ◽  
Price Series ◽  
Statistical Complexity ◽  
Electricity Spot Price ◽  
Insight Into ◽  
Refined Classification

In this study, we investigate the subtle temporal dynamics of California 1999–2000 spot price series based on permutation min-entropy (PME) and complexity-entropy causality plane. The dynamical transitions of price series are captured and the temporal correlations of price series are also discriminated by the recently introduced PME. Moreover, utilizing the CECP, we provide a refined classification of the monthly price dynamics and obtain an insight into the stochastic nature of price series. The results uncover that the spot price signal presents diverse temporal correlations and exhibits a higher stochastic behavior during the periods of crisis.

scholarly journals Host genetic variants associated with community-acquired pneumonia

Critical Care ◽  
2013 ◽  
Vol 17 (S2) ◽  
Author(s):  
LE Salnikova ◽  
TV Smelaya ◽  
VV Moroz ◽  
A Golubev ◽  
AV Rubanovich
Keyword(s):  
Genetic Variants ◽  
Community Acquired Pneumonia ◽  
Host Genetic

Variant calling and quality control of large-scale human genome sequencing data

2019 ◽  
Vol 3 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Brandon Jew ◽  
Jae Hoon Sul
Keyword(s):  
Quality Control ◽  
Genome Sequencing ◽  
Genetic Variants ◽  
Large Scale ◽  
Variant Calling ◽  
Sequencing Data ◽  
Computational Approaches ◽  
Sequencing Errors ◽  
Human Genome Sequencing ◽  
Number Of Individuals

Abstract Next-generation sequencing has allowed genetic studies to collect genome sequencing data from a large number of individuals. However, raw sequencing data are not usually interpretable due to fragmentation of the genome and technical biases; therefore, analysis of these data requires many computational approaches. First, for each sequenced individual, sequencing data are aligned and further processed to account for technical biases. Then, variant calling is performed to obtain information on the positions of genetic variants and their corresponding genotypes. Quality control (QC) is applied to identify individuals and genetic variants with sequencing errors. These procedures are necessary to generate accurate variant calls from sequencing data, and many computational approaches have been developed for these tasks. This review will focus on current widely used approaches for variant calling and QC.

scholarly journals Exponentially decaying modes and long-term prediction of sea ice concentration using Koopman mode decomposition

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
James Hogg ◽  
Maria Fonoberova ◽  
Igor Mezić
Keyword(s):  
Sea Ice ◽  
Annual Variation ◽  
Temporal Dynamics ◽  
The Arctic ◽  
Sea Ice Concentration ◽  
Mode Decomposition ◽  
Spatial Modes ◽  
Ice Concentration ◽  
The Mean ◽  
Insight Into

Abstract Sea ice cover in the Arctic and Antarctic is an important indicator of changes in the climate, with important environmental, economic and security consequences. The complexity of the spatio-temporal dynamics of sea ice makes it difficult to assess the temporal nature of the changes—e.g. linear or exponential—and their precise geographical loci. In this study, Koopman Mode Decomposition (KMD) is applied to satellite data of sea ice concentration for the Northern and Southern hemispheres to gain insight into the temporal and spatial dynamics of the sea ice behavior and to predict future sea ice behavior. We observe spatial modes corresponding to the mean and annual variation of Arctic and Antarctic sea ice concentration and observe decreases in the mean sea ice concentration from early to later periods, as well as corresponding shifts in the locations that undergo significant annual variation in sea ice concentration. We discover exponentially decaying spatial modes in both hemispheres and discuss their precise spatial extent, and also perform predictions of future sea ice concentration. The Koopman operator-based, data-driven decomposition technique gives insight into spatial and temporal dynamics of sea ice concentration not apparent in traditional approaches.

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