PXD006616 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | INKA, an integrative analysis pipeline for inference of hyperactive phosphokinases in mass spectrometry-based phosphoproteomics data |
Description | As a large proportion of current targeted cancer therapies is based on specific (tyrosine) kinase inhibitors, uncovering the identity of hyperactive kinases at work in tumors is crucial for proper treatment selection. A major challenge in phosphoproteomic data analysis is to relate kinases to the extent and magnitude of their phosphorylation 'footprint', and to rank them accordingly in order to single out kinases that are crucial for tumor growth in individual patients. Previous approaches have either zeroed in on phosphorylation of kinases themselves as a read-out of kinase activity, or focused on inferring kinase activities from the phosphorylation of their (supposed) substrates. Here, we combine both kinase-centric and substrate-centric analyses. We present a computational pipeline called Integrative Inferred Kinase Activity (INKA) scoring that integrates the observed abundance of phosphopeptides derived from (i) kinases as a whole, (ii) their kinase activation loop segments, (iii) proteins deduced to be kinase substrates based on prior experimental knowledge of kinase-substrate relationships, and/or (iv) kinase substrates predicted by the sequence motif- and network-based NetworKIN algorithm. As a proof of concept, applying this pipeline to the analysis of phosphoproteomic data on seven different oncogene-driven cancer cell lines highlighted the high, top ranking inferred activity of known driver kinases in these cells. This demonstrates the potential of label-free MS-based phosphoproteomics combined with dedicated data analysis for identifying (hyper)active kinases that, in potential future applications to tumors, may be selected for targeted inhibition in a personalized treatment setting. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:38:21.534.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Sander Piersma |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-05-29 05:07:44 | ID requested | |
1 | 2019-04-18 04:54:17 | announced | |
⏵ 2 | 2024-10-22 04:38:27 | announced | 2024-10-22: Updated project metadata. |
Publication List
Beekhof R, van Alphen C, Henneman AA, Knol JC, Pham TV, Rolfs F, Labots M, Henneberry E, Le Large TY, de Haas RR, Piersma SR, Vurchio V, Bertotti A, Trusolino L, Verheul HM, Jimenez CR, INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases. Mol Syst Biol, 15(4):e8250(2019) [pubmed] |
10.15252/msb.20188250; |
Keyword List
curator keyword: Technical, Biomedical |
submitter keyword: Human, single-shot, Tyrosine kinase, phosphokinase ranking, label-free, phosphoproteomics |
Contact List
Connie Ramona Jimenez |
contact affiliation | OncoProteomics Laboratory, Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands |
contact email | c.jimenez@vumc.nl |
lab head | |
Sander Piersma |
contact affiliation | OncoProteomics Laboratory, dept of Medical Oncology, VUmc Medical Center, Amsterdam, The Netherlands |
contact email | s.piersma@vumc.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006616
- Label: PRIDE project
- Name: INKA, an integrative analysis pipeline for inference of hyperactive phosphokinases in mass spectrometry-based phosphoproteomics data