Finding the “switch” in platelet activation Prediction of key mediators involved in platelet hyperreactivity using a novel network biology approach Article Swipe
TP Lemmens
,
DM Coenen
,
ICL Niessen
,
Frauke Swieringa
,
Slm Coort
,
RR Koenen
,
M Kutmon
,
Judith M.E.M. Cosemans
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-692247/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-692247/v1
The healthy endothelium controls platelet activity through release of prostaglandin I2 (PGI 2 ) and nitric oxide. The loss of this natural brake on platelet activity can cause platelets to become hyperreactive. PGI 2 attenuates platelet activation by adenosine diphosphate (ADP) through stimulation of cyclic adenosine monophosphate (cAMP) production and subsequent phosphorylation changes by protein kinase A (PKA). We hypothesize that proteins/processes involved in platelet hyperactivity downstream of the cAMP-PKA pathway can serve as a “switch” in platelet activation and inhibition. We designed a network biology approach to explore the entangled platelet signaling pathways downstream of PGI 2 and ADP. The STRING database was used to build a protein-protein interaction network from proteins of interest in which we integrate a quantitative platelet proteome dataset with pathway information, relative RNA expression of hematopoietic cells, the likelihood of the proteins being phosphorylated by PKA, and drug-target information from DrugBank in a biological network. We distilled 30 proteins from existing phosphoproteomics datasets (PXD000242 and PXD001189) that putatively can be “turned on” after ADP-mediated platelet activation and subsequently switched “off” after platelet inhibition with iloprost. Enrichment analysis revealed biological processes related to vesicle secretion and cytoskeletal reorganization to be overrepresented coinciding with topological clusters in the network. Our method highlights novel proteins related to vesicle transport, platelet shape change, and small GTPases as potential switch proteins in platelet activation and inhibition. Our novel approach demonstrates the benefit of data integration by combining tools and datasets and visualization to obtain a more complete picture of complex molecular mechanisms.
Related Topics
Concepts
Platelet activation
Platelet
Cell biology
Phosphoproteomics
Biology
Protein kinase A
Chemistry
Protein phosphorylation
Biochemistry
Phosphorylation
Immunology
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-692247/v1
- https://www.researchsquare.com/article/rs-692247/latest.pdf
- OA Status
- green
- References
- 25
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3207247980
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3207247980Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-692247/v1Digital Object Identifier
- Title
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Finding the “switch” in platelet activation Prediction of key mediators involved in platelet hyperreactivity using a novel network biology approachWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-08-24Full publication date if available
- Authors
-
TP Lemmens, DM Coenen, ICL Niessen, Frauke Swieringa, Slm Coort, RR Koenen, M Kutmon, Judith M.E.M. CosemansList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-692247/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-692247/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-692247/latest.pdfDirect OA link when available
- Concepts
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Platelet activation, Platelet, Cell biology, Phosphoproteomics, Biology, Protein kinase A, Chemistry, Protein phosphorylation, Biochemistry, Phosphorylation, ImmunologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
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25Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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