PXD018241-1

PXD018241 is an original dataset announced via ProteomeXchange.

Title	Characterisation of the transcriptome and proteome of SARS-CoV-2 using direct RNA sequencing and tandem mass spectrometry reveals evidence for a cell passage induced in-frame deletion in the spike glycoprotein that removes the furin-like cleavage site.
Description	Direct RNA sequencing using an Oxford Nanopore MinION characterised the transcriptome of SARS-CoV-2 grown in Vero E6 cells. This cell line is being widely used to propagate the novel coronavirus. The viral transcriptome was analysed using a recently developed ORF-centric pipeline. This revealed the pattern of viral transcripts, (i.e. subgenomic mRNAs), generally fitted the predicted replication and transcription model for coronaviruses. A 24 nt in-frame deletion was detected in subgenomic mRNAs encoding the spike (S) glycoprotein. This feature was identified in over half of the mapped transcripts and was predicted to remove a proposed furin cleavage site from the S glycoprotein. This motif directs cleavage of the S glycoprotein into functional subunits during virus entry or exit. Cleavage of the S glycoprotein can be a barrier to zoonotic coronavirus transmission and affect viral pathogenicity. Allied to this transcriptome analysis, tandem mass spectrometry was used to identify over 500 viral peptides and 44 phosphopeptides, covering almost all of the proteins predicted to be encoded by the SARS-CoV-2 genome, including peptides unique to the deleted variant of the S glycoprotein. Detection of an apparently viable deletion in the furin cleavage site of the S glycoprotein reinforces the point that this and other regions of SARS-CoV-2 proteins may readily mutate. This is of clear significance given the interest in the S glycoprotein as a potential vaccine target and the observation that the furin cleavage site likely contributes strongly to the pathogenesis and zoonosis of this virus. The viral genome sequence should be carefully monitored during the growth of viral stocks for research, animal challenge models and, potentially, in clinical samples. Such variations may result in different levels of virulence, morbidity and mortality.
HostingRepository	PRIDE
AnnounceDate	2020-03-31
AnnouncementXML	Submission_2020-03-31_01:53:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yasset Perez-Riverol
SpeciesList	scientific name: Chlorocebus sabaeus; NCBI TaxID: 60711;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-29 08:42:24	ID requested
⏵ 1	2020-03-31 01:53:58	announced

Dataset with its publication pending

submitter keyword: Human, SARS-CoV-2, Coronavirus, Multiomics

David A. Matthews
contact affiliation	School of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD
contact email	d.a.matthews@bristol.ac.uk
lab head
Yasset Perez-Riverol
contact affiliation	EBI
contact email	yperez@ebi.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018241
     1. Label: PRIDE project
     2. Name: Characterisation of the transcriptome and proteome of SARS-CoV-2 using direct RNA sequencing and tandem mass spectrometry reveals evidence for a cell passage induced in-frame deletion in the spike glycoprotein that removes the furin-like cleavage site.