Reuse of public data in proteomics

Exploring the potential of public
proteomics data
Dr. Juan Antonio Vizcaíno
Proteomics Team Leader
EMBL-EBI
Hinxton, Cambridge, UK

Juan A. Vizcaíno
juan@ebi.ac.uk
WT Proteomics Bioinformatics Course 2016
Hinxton, 8 December 2016
Datasets are being reused more and more….
Vaudel et al., Proteomics, 2016
Data download volume for
PRIDE Archive in 2015: 198 TB
0
50
100
150
200
250
2013 2014 2015 2016
Downloads in TBs

Juan A. Vizcaíno
juan@ebi.ac.uk
Data sharing in Proteomics
Vaudel et al., Proteomics, 2016

Juan A. Vizcaíno
juan@ebi.ac.uk

Juan A. Vizcaíno
juan@ebi.ac.uk
• Data as they are.
• Protein knowledge bases: UniProt, neXtProt.
• Contributing to the Protein Evidence Code.

Juan A. Vizcaíno
juan@ebi.ac.uk
Protein Evidence codes in UniProt/neXtProt
http://www.uniprot.org/help/protein_existence

Juan A. Vizcaíno
juan@ebi.ac.uk
Use of MS data in UniProt

Juan A. Vizcaíno
juan@ebi.ac.uk
Use of MS data in neXtProt

Juan A. Vizcaíno
juan@ebi.ac.uk
Reuse
• Information is not only extracted, but reused in new
experiments with the potential of generating new
knowledge.
• Transitions used in SRM approaches.
• Meta-analysis approaches.
• Spectral libraries.

Juan A. Vizcaíno
juan@ebi.ac.uk
SRMAtlas
http://www.srmatlas.org/

Juan A. Vizcaíno
juan@ebi.ac.uk
PeptidePicker
http://mrmpeptidepicker.proteincentre.com/

Juan A. Vizcaíno
juan@ebi.ac.uk
Meta-analysis approaches
• Putting data coming from a lot of experiments
together, to extract new knowledge. Examples:
• Study the cleavage mechanism and performance of
trypsin.
• Fragmentation patterns.
• Retention time prediction.
• Which is the most suitable reference DB for long-term
proteomics data storage?
• Data integration of experiments done at different time
points.

Juan A. Vizcaíno
juan@ebi.ac.uk
Spectral searching
• Concept: To compare experimental spectra to other
experimental spectra.
• There are many spectral libraries publicly available (for
instance, from NIST, PeptideAtlas and PRIDE)
• Custom ‘search engines’ have been developed:
• SpectraST (TPP)
• X!Hunter (GPM)
• Bibliospec
• It has been claimed that the searches have more
sensitivity that with sequence database approaches

Juan A. Vizcaíno
juan@ebi.ac.uk
Spectral searching (2)
http://peptide.nist.gov/

Juan A. Vizcaíno
juan@ebi.ac.uk
PRIDE Cluster as a Public Data Mining Resource
17
• http://www.ebi.ac.uk/pride/cluster
• Spectral libraries for 16 species.
• All clustering results, as well as specific subsets of interest available.
• Source code (open source) and Java API

Juan A. Vizcaíno
juan@ebi.ac.uk
Reprocess
• Data are reprocessed with the intention of obtaining
new knowledge or to provide an updated view on the
results.
• It mainly serves the same purpose of the original
experiment.
• For instance, a shot-gun dataset can be reprocessed
with a different algorithm or an updated sequence
database.

Juan A. Vizcaíno
juan@ebi.ac.uk
Reprocessing repositories
• These resources collect MS raw data and reprocess it using
one given analysis pipeline, and an up-to date protein
sequence database.
• Main resources: GPMDB and PeptideAtlas (ISB, Seattle).

Juan A. Vizcaíno
juan@ebi.ac.uk
PeptideAtlas and GPMDB

Juan A. Vizcaíno
juan@ebi.ac.uk
Draft Human proteome papers published in 2014
Wilhelm et al., Nature, 2014
•Around 60% of the data used for the
analysis comes from previous
experiments, most of them stored in
proteomics repositories such as
PRIDE/ProteomeXchange, PASSEL or
MassIVE.
•They complement that data with “exotic”
tissues.

Juan A. Vizcaíno
juan@ebi.ac.uk
Reprocessing for the validation of controversial data
• Analysis of Tyrannosaurus rex fossils: controversial presence of
collagen (is it a contamination of the sample? Did the sample contain
any T. rex proteins at all?)
Asara et al. (2007) Science 316: 280-5.
Asara et al. (2007) Science 316: 1324-5.
Bern et al. (2009) JPR 9: 4328-32
PRIDE Archive assay accession
8633

Juan A. Vizcaíno
juan@ebi.ac.uk
Info from R. Chalkley
Bromenshenk et al. (2011) PLOS One 5: e13181
Reprocessing for the validation of controversial data (2)

Juan A. Vizcaíno
juan@ebi.ac.uk
Experimental Protocol
1. Collected samples from healthy, collapsing and collapsed bee colonies.
2. Homogenised bees.
3. Digested with Trypsin
4. Analyzed by LC-MSMS on LTQ
5. Searched using Sequest
6. Filtered Results using Peptide and Protein Prophet
7. Performed further analysis to determine species statistically more
commonly found in collapsing/collapsed colony samples
Bromenshenk et al. (2011) PLOS One 5: e13181

Juan A. Vizcaíno
juan@ebi.ac.uk
• Big pitfall: Search database was only composed by viral
proteins. Not bee proteins at all!!
• After researching the data, there is no evidence for viral
peptides/proteins in any of their data: honey bee, fruit fly,
wasp, moth, human keratin, bacteria that like sugary
environments, …
• “We believe that there is currently insufficient evidence to
conclude that bees are a natural host for IIV-6, let alone that
the virus is linked to CCD”.
Knudsen & Chalkley (2011) PLOS One 6:
e20873
Foster (2011), MCP 10: M110.006387

Juan A. Vizcaíno
juan@ebi.ac.uk
Reprocessing for the validation of controversial data
Datasets PXD000561 and PXD000865 in PRIDE Archive

Juan A. Vizcaíno
juan@ebi.ac.uk
Various reanalysis of these datasets have been performed…
Reanalysis of Pandey dataset (Nature, 2014) made by J. Choudhary’s group at
Sanger Institute
Wright et al., Nat Commun, 2016Dataset PXD000561
http://www.ebi.ac.uk/gxa

Juan A. Vizcaíno
juan@ebi.ac.uk
Repurposing
• Data are considered in light of a question or a context
that is different from the original study.
• Proteogenomics studies
• Discovery of novel PTMs.

Juan A. Vizcaíno
juan@ebi.ac.uk
Examples of repurposing datasets: proteogenomics
Data in public resources can be used for genome annotation purposes

Juan A. Vizcaíno
juan@ebi.ac.uk
Repurposing: new PTMs found
• Individual authors can reprocess raw data with new
hypotheses in mind (not taken into account by the original
authors).
• Recent examples (using phosphoproteomics data sets):
• O-GlcNAc-6-phosphate1
• Phosphoglyceryl2
• ADP-ribosylation3
1Hahne & Kuster, Mol Cell Proteomics (2012) 11 10 1063-9
2Moellering & Cravatt, Science (2013) 341 549-553
3Matic et al., Nat Methods (2012) 9 771-2

Juan A. Vizcaíno
juan@ebi.ac.uk
Vaudel M, Barsnes H, Berven FS, Sickmann A,
Martens L:
Proteomics 2011;11(5):996-9.
https://github.com/compomics/searchgui https://github.com/compomics/peptide-shaker
Vaudel M, Burkhart J, Zahedi RP, Berven FS, Sickmann A, Martens L,
Barsnes H:
Nature Biotechnology 2015; 33(1):22-4.
CompOmics Open Source Analysis Pipeline

Juan A. Vizcaíno
juan@ebi.ac.uk
Find the desired PRIDE project …
… and start re-analyzing the data!
… inspect the project details ….
Reshake PRIDE data!

Juan A. Vizcaíno
juan@ebi.ac.uk
Public datasets from different omics: OmicsDI
http://www.ebi.ac.uk/Tools/omicsdi/
• Aims to integrate of ‘omics’ datasets (proteomics,
transcriptomics, metabolomics and genomics at present).
PRIDE
MassIVE
jPOST
PASSEL
GPMDB
ArrayExpress
Expression Atlas
MetaboLights
Metabolomics Workbench
GNPS
EGA
Perez-Riverol et al., Nat Biotechnol, in press

Juan A. Vizcaíno
juan@ebi.ac.uk
OmicsDI: Portal for omics datasets

Juan A. Vizcaíno
juan@ebi.ac.uk
Acknowledgements
http://www.ncbi.nlm.nih.gov/pubmed/26449181
http://onlinelibrary.wiley.com/doi/10.1002/pmic.201500295/epdf

Juan A. Vizcaíno
juan@ebi.ac.uk
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Reuse of public data in proteomics

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