Dataset Information

Pattern of genomic variation in SARS-CoV-2 (COVID-19) suggests restricted nonrandom changes: Analysis using Shewhart control charts.

ABSTRACT: SARS-CoV-2 is a member of the Coronavirus family which recently originated from the Wuhan province of China and spread very rapidly through the world infecting more than 4 million people. In the past, other Coronaviruses have also been found to cause human infection, but not as widespread as COVID-19. Since Coronavirus sequences constantly change due to mutation and recombination, it is important to understand the pattern of changes and likely path the virus can take in the future. In this study, we have used the Shewhart control chart to identify and analyze hypervariable (hotspots) and hypovariable (coldspots) regions of the virus. Our analysis shows that SARS-CoV-2 has changed in a few regions of the genome. Analysis of SARS-CoV-1 and MERS sequences suggests that over time, mutations start accumulating in different regions and most likely SARS-CoV-2 may also follow a similar path. The results suggest a possible emergence of modified viruses over some time.

SUBMITTER: Mandal S

PROVIDER: S-EPMC7856336 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pattern of genomic variation in SARS-CoV-2 (COVID-19) suggests restricted nonrandom changes: Analysis using Shewhart control charts.

Mandal Saurav S Roychowdhury Tanmoy T Bhattacharya Alok A

Journal of biosciences 20210101

SARS-CoV-2 is a member of the Coronavirus family which recently originated from the Wuhan province of China and spread very rapidly through the world infecting more than 4 million people. In the past, other Coronaviruses have also been found to cause human infection, but not as widespread as COVID-19. Since Coronavirus sequences constantly change due to mutation and recombination, it is important to understand the pattern of changes and likely path the virus can take in the future. In this study ...[more]

PMID: 33709963

Similar Datasets

Project description:The outbreak of coronavirus disease 2019 (COVID-19) that started in Wuhan, China, in December 2019 has spread worldwide, emerging as a global pandemic. The severe respiratory pneumonia caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far claimed more than 0.38 million lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 virus displays high transmission rates, the underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries, suggesting that its spread is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nonstructural protein 13 (nsp13), nsp14, nsp15, and nsp16 (ORF1b polyproteins) and in the S-protein within 10 viral isolates from the United States. These viral proteins are involved in RNA replication and binding with the human receptors, indicating that the viral variants that are circulating in the population of the United States are different from those circulating in the populations of other countries. In addition, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of a U.S. isolate (GenBank accession no. MT188341.1) leading to a shift in the amino acid frame from position 2540 onward. Through comparative structural analysis of the wild-type and mutant proteins, we showed that this addition of a phenylalanine residue renders the protein in the mutant less stable, which might affect mRNA cap-1 methyltransferase function. We further analyzed the SARS-CoV-2-human interactome, which revealed that the interferon signaling pathway is targeted by orf1ab during infection and that it also interacts with NF-κB-repressing factor (NKRF), which is a potential regulator of interleukin-8 (IL-8). We propose that targeting this interaction may subsequently improve the health condition of COVID-19 patients. Our analysis also emphasized that SARS-CoV-2 manipulates spliceosome machinery during infection; hence, targeting splicing might affect viral replication. In conclusion, the replicative machinery of SARS-CoV-2 is targeting interferon and the notch signaling pathway along with spliceosome machinery to evade host challenges.IMPORTANCE The COVID-19 pandemic continues to storm the world, with over 6.5 million cases worldwide. The severity of the disease varies with the territories and is mainly influenced by population density and age factor. In this study, we analyzed the transmission pattern of 95 SARS-CoV-2 genomes isolated from 11 different countries. Our study also revealed several nonsynonymous mutations in ORF1b and S-proteins and the impact on their structural stability. Our analysis showed the manipulation of host system by viral proteins through SARS-CoV-2-human protein interactome, which can be useful to understand the impact of virus on human health.

Project description:The severe acute respiratory coronavirus 2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. The epidemic accelerated in Philadelphia, PA, in the spring of 2020, with the city experiencing a first peak of infections on 15 April, followed by a decline through midsummer. Here, we investigate spread of the epidemic in the first wave in Philadelphia using full-genome sequencing of 52 SARS-CoV-2 samples obtained from 27 hospitalized patients collected between 30 March and 17 July 2020. Sequences most commonly resembled lineages circulating at earlier times in New York, suggesting transmission primarily from this location, though a minority of Philadelphia genomes matched sequences from other sites, suggesting additional introductions. Multiple genomes showed even closer matches to other Philadelphia isolates, suggestive of ongoing transmission within Philadelphia. We found that all of our isolates contained the D614G substitution in the viral spike and belong to lineages variously designated B.1, Nextstrain clade 20A or 20C, and GISAID clade G or GH. There were no viral sequence polymorphisms detectably associated with disease outcome. For some patients, genome sequences were determined longitudinally or concurrently from multiple body sites. In both cases, some comparisons showed reproducible polymorphisms, suggesting initial seeding with multiple variants and/or accumulation of polymorphisms after infection. These results thus provide data on the sources of SARS-CoV-2 infection in Philadelphia and begin to explore the dynamics within hospitalized patients.IMPORTANCE Understanding how SARS-CoV-2 spreads globally and within infected individuals is critical to the development of mitigation strategies. We found that most lineages in Philadelphia had resembled sequences from New York, suggesting infection primarily but not exclusively from this location. Many genomes had even nearer neighbors within Philadelphia, indicating local spread. Multiple genome sequences were available for some subjects and in a subset of cases could be shown to differ between time points and body sites within an individual, indicating heterogeneous viral populations within individuals and raising questions on the mechanisms responsible. There was no evidence that different lineages were associated with different outcomes in patients, emphasizing the importance of individual-specific vulnerability.

Dataset Information

Pattern of genomic variation in SARS-CoV-2 (COVID-19) suggests restricted nonrandom changes: Analysis using Shewhart control charts.

Publications

Pattern of genomic variation in SARS-CoV-2 (COVID-19) suggests restricted nonrandom changes: Analysis using Shewhart control charts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets