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1.
Nucleic Acids Res ; 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1784376

ABSTRACT

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called 'Dynamic' tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329048

ABSTRACT

Background: The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral-pharynx in the context of SARS-CoV-2 and other viral infections, hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputum, and 152 faecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load;and microbial community in upper respiratory tract renders high risk of antibiotic resistance. Longitudinally, microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

4.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
5.
6.
Natl Sci Rev ; 8(4): nwab006, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1254806

ABSTRACT

After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.

7.
Mol Cell ; 80(6): 1123-1134.e4, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-939163

ABSTRACT

Analyzing the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from clinical samples is crucial for understanding viral spread and evolution as well as for vaccine development. Existing RNA sequencing methods are demanding on user technique and time and, thus, not ideal for time-sensitive clinical samples; these methods are also not optimized for high performance on viral genomes. We developed a facile, practical, and robust approach for metagenomic and deep viral sequencing from clinical samples. We demonstrate the utility of our approach on pharyngeal, sputum, and stool samples collected from coronavirus disease 2019 (COVID-19) patients, successfully obtaining whole metatranscriptomes and complete high-depth, high-coverage SARS-CoV-2 genomes with high yield and robustness. With a shortened hands-on time from sample to virus-enriched sequencing-ready library, this rapid, versatile, and clinic-friendly approach will facilitate molecular epidemiology studies during current and future outbreaks.


Subject(s)
COVID-19/genetics , Genome, Viral , High-Throughput Nucleotide Sequencing , RNA, Viral/genetics , SARS-CoV-2/genetics , Whole Genome Sequencing , Animals , Humans , Mice , NIH 3T3 Cells , RNA, Viral/metabolism , SARS-CoV-2/metabolism
8.
Nat Commun ; 11(1): 5503, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894393

ABSTRACT

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Beijing/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Female , Genome, Viral , Genomics , Genotype , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Polymorphism, Single Nucleotide , SARS-CoV-2 , Travel , Young Adult
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