Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences.
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ABSTRACT:
SUBMITTER: Ugurel OM
PROVIDER: S-EPMC8573839 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSince the onset of the SARS-CoV-2 pandemic, bioinformatic analyses have been performed to understand the nucleotide and synonymous codon usage features and mutational patterns of the virus. However, comparatively few have attempted to perform such analyses on a considerably large cohort of viral genomes while organizing the plethora of available sequence data for a month-by-month analysis to observe changes over time. Here, we aimed to perform sequence composition and mutation analysis of SARS-CoV-2, separating sequences by gene, clade, and timepoints, and contrast the mutational profile of SARS-CoV-2 to other comparable RNA viruses.MethodsUsing a cleaned, filtered, and pre-aligned dataset of over 3.5 million sequences downloaded from the GISAID database, we computed nucleotide and codon usage statistics, including calculation of relative synonymous codon usage values. We then calculated codon adaptation index (CAI) changes and a nonsynonymous/synonymous mutation ratio (dN/dS) over time for our dataset. Finally, we compiled information on the types of mutations occurring for SARS-CoV-2 and other comparable RNA viruses, and generated heatmaps showing codon and nucleotide composition at high entropy positions along the Spike sequence.ResultsWe show that nucleotide and codon usage metrics remain relatively consistent over the 32-month span, though there are significant differences between clades within each gene at various timepoints. CAI and dN/dS values vary substantially between different timepoints and different genes, with Spike gene on average showing both the highest CAI and dN/dS values. Mutational analysis showed that SARS-CoV-2 Spike has a higher proportion of nonsynonymous mutations than analogous genes in other RNA viruses, with nonsynonymous mutations outnumbering synonymous ones by up to 20:1. However, at several specific positions, synonymous mutations were overwhelmingly predominant.ConclusionsOur multifaceted analysis covering both the composition and mutation signature of SARS-CoV-2 gives valuable insight into the nucleotide frequency and codon usage heterogeneity of SARS-CoV-2 over time, and its unique mutational profile compared to other RNA viruses.
| S-EPMC9936480 | biostudies-literature
Project description:We present a large-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) substitutions, considering 1,585,456 high-quality raw sequencing samples, aimed at investigating the existence and quantifying the effect of mutational processes causing mutations in SARS-CoV-2 genomes when interacting with the human host. As a result, we confirmed the presence of three well-differentiated mutational processes likely ruled by reactive oxygen species (ROS), apolipoprotein B editing complex (APOBEC), and adenosine deaminase acting on RNA (ADAR). We then evaluated the activity of these mutational processes in different continental groups, showing that some samples from Africa present a significantly higher number of substitutions, most likely due to higher APOBEC activity. We finally analyzed the activity of mutational processes across different SARS-CoV-2 variants, and we found a significantly lower number of mutations attributable to APOBEC activity in samples assigned to the Omicron variant.
| S-EPMC9864147 | biostudies-literature
Project description:BackgroundThe COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the accuracy and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada.ResultsWe found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high accuracy when predicting epidemiologically informed clusters from sequence data.ConclusionsOur new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.
| S-EPMC9579665 | biostudies-literature
Project description:The raw material for viral evolution is provided by intra-host mutations occurring during replication, transcription or post-transcription. Replication and transcription of Coronaviridae proceed through the synthesis of negative-sense 'antigenomes' acting as templates for positive-sense genomic and subgenomic RNA. Hence, mutations in the genomes of SARS-CoV-2 and other coronaviruses can occur during (and after) the synthesis of either negative-sense or positive-sense RNA, with potentially distinct patterns and consequences. We explored for the first time the mutational spectrum of SARS-CoV-2 (sub)genomic and anti(sub)genomic RNA. We use a high-quality deep sequencing dataset produced using a quantitative strand-aware sequencing method, controlled for artefacts and sequencing errors, and scrutinized for accurate detection of within-host diversity. The nucleotide differences between negative- and positive-sense strand consensus vary between patients and do not show dependence on age or sex. Similarities and differences in mutational patterns between within-host minor variants on the two RNA strands suggested strand-specific mutations or editing by host deaminases and oxidative damage. We observe generally neutral and slight negative selection on the negative strand, contrasting with purifying selection in ORF1a, ORF1b and S genes of the positive strand of the genome.
| S-EPMC9667359 | biostudies-literature
Project description:The number of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases is increasing in India. This study looks upon the geographic distribution of the virus clades and variants circulating in different parts of India between January and August 2020. The NPS/OPS from representative positive cases from different states and union territories in India were collected every month through the VRDLs in the country and analyzed using next-generation sequencing. Epidemiological analysis of the 689 SARS-CoV-2 clinical samples revealed GH and GR to be the predominant clades circulating in different states in India. The northern part of India largely reported the 'GH' clade, whereas the southern part reported the 'GR', with a few exceptions. These sequences also revealed the presence of single independent mutations-E484Q and N440K-from Maharashtra (first observed in March 2020) and Southern Indian States (first observed in May 2020), respectively. Furthermore, this study indicates that the SARS-CoV-2 variant (VOC, VUI, variant of high consequence and double mutant) was not observed during the early phase of virus transmission (January-August). This increased number of variations observed within a short timeframe across the globe suggests virus evolution, which can be a step towards enhanced host adaptation.
| S-EPMC8156686 | biostudies-literature
Project description:SARS-CoV-2 has infected more than 600 million people. However, the origin of the virus is still unclear; knowing where the virus came from could help us prevent future zoonotic epidemics. Sequencing data, particularly metagenomic data, can profile the genomes of all species in the sample, including those not recognized at the time, thus allowing for the identification of the progenitor of SARS-CoV-2 in samples collected before the pandemic. We analyzed the data from 5,196 SARS-CoV-2-positive sequencing runs in the NCBI's SRA database with collection dates prior to 2020 or unknown. We found that the mutation patterns obtained from these suspicious SARS-CoV-2 reads did not match the genome characteristics of an unknown progenitor of the virus, suggesting that they may derive from circulating SARS-CoV-2 variants or other coronaviruses. Despite a negative result for tracking the progenitor of SARS-CoV-2, the methods developed in the study could assist in pinpointing the origin of various pathogens in the future. IMPORTANCE Sequences that are homologous to the SARS-CoV-2 genome were found in numerous sequencing runs that were not associated with the SARS-CoV-2 studies in the public database. It is unclear whether they are derived from the possible progenitor of SARS-CoV-2 or contamination of more recent SARS-CoV-2 variants circulated in the population due to the lack of information on the collection, library preparation, and sequencing processes. We have developed a computational framework to infer the evolutionary relationship between sequences based on the comparison of mutations, which enabled us to rule out the possibility that these suspicious sequences originate from unknown progenitors of SARS-CoV-2.
| S-EPMC9927258 | biostudies-literature
Project description:The increasing popularity of cytochrome c oxidase subunit 1 (COI) DNA metabarcoding warrants a careful look at the underlying reference databases used to make high-throughput taxonomic assignments. The objectives of this study are to document trends and assess the future usability of COI records for metabarcode identification. The number of COI records deposited to the NCBI nucleotide database has increased by a geometric average of 51% per year, from 8,137 records deposited in 2003 to a cumulative total of ~ 2.5 million by the end of 2017. About half of these records are fully identified to the species rank, 92% are at least 500 bp in length, 74% have a country annotation, and 51% have latitude-longitude annotations. To ensure the future usability of COI records in GenBank we suggest: 1) Improving the geographic representation of COI records, 2) Improving the cross-referencing of COI records in the Barcode of Life Data System and GenBank to facilitate consolidation and incorporation into existing bioinformatic pipelines, 3) Adherence to the minimum information about a marker gene sequence guidelines, and 4) Integrating metabarcodes from eDNA and mixed community studies with existing reference sequences. The growth of COI reference records over the past 15 years has been substantial and is likely to be a resource across many fields for years to come.
| S-EPMC6128447 | biostudies-literature
Project description:Background and objectivesIn first May 2020, Indonesia has been successfully submitted the first three full-length sequence of SARS-CoV-2 to GISAID database. Until September 10th, 2020, Indonesia had submitted 54 WGS. In this study, we have analyzed and annotated SARS-CoV-2 mutations in spike protein and main proteases.Materials and methodsThe Whole Genome Sequence (WGS) of Indonesia were obtained from GISAID data base. The 54 data were taken from March to September 10th, 2020. The sequences corresponded to Spike Protein (SP), 3-chymotrypsin like protease (3CLpro), and papain like protease (PLpro) were selected. The Wuhan genome was used as reference.ResultsIn total WGS from Indonesia, we found 5 major clades, which dominated as G clade, where the mutation of D614G was found. This D614G was identified as much as 59%, which mostly reported in late samples submitted. Beside D614G mutation, we report three unique mutations: A352S, S477I, and Q677H. Besides, some mutations were also detected in two domains that were expected to be conserved region, the main viral proteases: PLpro (P77L and V205I), 3CLpro (M49I and L50F).ConclusionThe analysis of SARS-CoV-2 from WGS Indonesia showed a high genetic variation. The diversity in SARS-CoV-2 may epidemiologically enhance virulence and transmission of this virus. The prevalence of D614G over the time in different locations, indicating that changes in this mutation may related to host infection and the viral transmission. However, some mutations that have been reported in this study were not eligible for the most stable conformation.
| S-EPMC8408024 | biostudies-literature
Project description:SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-κB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.
| S-EPMC7980187 | biostudies-literature
Project description:Here, we report the genomic sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from nasopharyngeal samples from five tested coronavirus disease 2019 (COVID-19)-infected patients from the Lambayeque region in Peru during early April 2020.
| S-EPMC8407726 | biostudies-literature