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1.
Nat Commun ; 13(1): 3645, 2022 06 25.
Article in English | MEDLINE | ID: covidwho-1908172

ABSTRACT

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.


Subject(s)
COVID-19 , Superinfection , Genome, Viral/genetics , Humans , New York City/epidemiology , Recombination, Genetic , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
2.
Mol Biol Evol ; 39(4)2022 04 11.
Article in English | MEDLINE | ID: covidwho-1758789

ABSTRACT

Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , COVID-19/genetics , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321087

ABSTRACT

The COVID-19 pandemic is shifting the teaching paradigms to an online setting all over the world. The Galaxy framework caters to computational biologists a set of features to facilitate the online learning process and make it accessible to everyone. Besides the high-quality training materials, Galaxy provides easy access to data and the possibility to share the progress and achievements, both student to student and student to instructor. By combining the different features offered by the Galaxy framework and by choosing the adequate communication channels, effective training activities can be designed inclusively, regardless of the students' environments.

4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294859

ABSTRACT

Protein-protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein-protein interactions and produce high-quality multimeric structural models. Application of our method to the Human and Yeast genomes yield protein-protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2’s non-structural protein 3 (Nsp3). We also produced models of SARS-CoV2’s spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor (MOG) and dipeptidyl peptidase-4 (DPP4). The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation. The interactome modeling pipeline is available at usegalaxy.org and usegalaxy.eu.

6.
Mol Biol Evol ; 38(12): 5678-5684, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1402409

ABSTRACT

The programmed frameshift element (PFE) rerouting translation from ORF1a to ORF1b is essential for the propagation of coronaviruses. The combination of genomic features that make up PFE-the overlap between the two reading frames, a slippery sequence, as well as an ensemble of complex secondary structure elements-places severe constraints on this region as most possible nucleotide substitution may disrupt one or more of these elements. The vast amount of SARS-CoV-2 sequencing data generated within the past year provides an opportunity to assess the evolutionary dynamics of PFE in great detail. Here, we performed a comparative analysis of all available coronaviral genomic data available to date. We show that the overlap between ORF1a and ORF1b evolved as a set of discrete 7, 16, 22, 25, and 31 nucleotide stretches with a well-defined phylogenetic specificity. We further examined sequencing data from over 1,500,000 complete genomes and 55,000 raw read data sets to demonstrate exceptional conservation and detect signatures of selection within the PFE region.


Subject(s)
Coronavirus/genetics , Open Reading Frames , Phylogeny , SARS-CoV-2/genetics , Nucleotides
7.
PLoS Comput Biol ; 17(5): e1008923, 2021 05.
Article in English | MEDLINE | ID: covidwho-1226887

ABSTRACT

The COVID-19 pandemic is shifting teaching to an online setting all over the world. The Galaxy framework facilitates the online learning process and makes it accessible by providing a library of high-quality community-curated training materials, enabling easy access to data and tools, and facilitates sharing achievements and progress between students and instructors. By combining Galaxy with robust communication channels, effective instruction can be designed inclusively, regardless of the students' environments.


Subject(s)
COVID-19/epidemiology , Computer-Assisted Instruction , Education, Distance/organization & administration , COVID-19/virology , Computational Biology , Humans , Information Dissemination , Pandemics , SARS-CoV-2/isolation & purification
8.
PLoS Pathog ; 16(8): e1008643, 2020 08.
Article in English | MEDLINE | ID: covidwho-712942

ABSTRACT

The current state of much of the Wuhan pneumonia virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies and requires unimpeded access to data, analysis tools, and computational infrastructure. Here, we show that community efforts in developing open analytical software tools over the past 10 years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all SARS-CoV-2 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Pneumonia, Viral/virology , Public Health , Severe Acute Respiratory Syndrome/virology , COVID-19 , Data Analysis , Humans , Pandemics , SARS-CoV-2
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