PXD046874-1

PXD046874 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation in the Plasmodium falciparum proteome: A meta-analysis of publicly available data sets
Description	Malaria is a deadly disease caused by Apicomplexan parasites of the Plasmodium genus. Several species of the Plasmodium genus are known to be infectious to human, of which P. falciparum is the deadliest. Post-translational modifications (PTMs) of proteins coordinate cell signalling and hence, regulate many biological processes in P. falciparum homeostasis and host infection, of which the most highly studied is phosphorylation. Phosphosites on proteins can be identified by tandem mass spectrometry (MS) performed on enriched samples (phosphoproteomics), followed by downstream computational analyses. We have performed a large-scale meta-analysis of 11 publicly available phosphoproteomics datasets, to build a comprehensive atlas of phosphosites in the P. falciparum proteome, using robust pipelines aimed at strict control of false identifications. We identified a total of 28,495 phosphorylated sites on P. falciparum proteins at 5% false localisation rate (FLR) and, of those, 18,100 at 1% FLR. We identified significant sequence motifs, likely indicative of different groups of kinases, responsible for different groups of phosphosites. Conservation analysis identified clusters of phosphoproteins that are highly conserved, and others that are evolving faster within the Plasmodium genus, and implicated in different pathways. We also explored the structural context of phosphosites, identifying a strong enrichment for phosphosites on fast evolving (low conservation) intrinsically disordered regions (IDRs) of proteins. In other species, IDRs have been shown to have an important role in modulating protein-protein interactions, particularly in signalling, and thus warranting further study for their roles in host-pathogen interactions. All data has made available via UniProt, PRIDE and PeptideAtlas, with visualisation interfaces for exploring phosphosites in the context of other data on Plasmodium proteins.We have re-analysed publicly available mass spectrometry (MS) data sets enriched for phosphopeptides from Asian rice (Oryza sativa). In total we have identified, 15522 phosphosites on Serine, Threonine and Tyrosine residues on rice proteins. The data has been loaded into UniProtKB, enabling researchers to visualise the sites alongside other stored data on rice proteins, including structural models from AlphaFold2, and into PeptideAtlas, enabling visualisation of the source evidence for each site, including scores and source mass spectra. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation caused by different kinase groups. We cross-referenced phosphosites against single amino acid variation (SAAV) data sourced from the rice 3000 genomes data, to identify SAAVs within or proximal to phosphosites that could cause loss of a particular site in a given rice variety. The data was further clustered to identify groups of sites with similar patterns across rice family groups, allowing us to identify sites highly conserved in Japonica, but mostly absent in, for example, Aus type rice varieties - known to have different responses to drought. These resources can assist rice researchers to discover alleles with significantly different functional effects across rice varieties.
HostingRepository	PRIDE
AnnounceDate	2023-11-22
AnnouncementXML	Submission_2023-11-22_09:46:38.429.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD046874
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yasset Perez-Riverol
SpeciesList	scientific name: Plasmodium falciparum; NCBI TaxID: NCBITaxon:5833;
ModificationList	phosphorylated residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-12 13:29:58	ID requested
⏵ 1	2023-11-22 09:46:38	announced
2	2024-10-22 06:15:43	announced	2024-10-22: Updated project metadata.

10.6019/PXD046874;

submitter keyword: Phosphoproteomics, PTMeXchange, FLR, public data,Reanalysis

Andrew R Jones
contact affiliation	Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3BX, United Kingdom
contact email	jonesar@liverpool.ac.uk
lab head
Yasset Perez-Riverol
contact affiliation	EBI
contact email	yperez@ebi.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/11/PXD046874

PRIDE project URI

• PRIDE
  1. PXD046874
     1. Label: PRIDE project
     2. Name: Phosphorylation in the Plasmodium falciparum proteome: A meta-analysis of publicly available data sets