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Benchmarking substrate-based kinase activity inference using phosphoproteomic data
[article]
2016
bioRxiv
pre-print
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It has been proposed that changes in phosphorylation of kinase target sites can be used to infer when a kinase activity is under regulation. ...
A list of kinase substrates was compiled and used to estimate changes in kinase activities using the following methods: Z-test, Kolmogorov Smirnov test, Wilcoxon rank sum test, gene set enrichment analysis ...
doi:10.1101/080978
fatcat:p6lwz2tj2vgbjpowcjhp5s34tm
Benchmarking substrate-based kinase activity inference using phosphoproteomic data
2017
Bioinformatics
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It has been proposed that changes in phosphorylation of kinase target sites can be used to infer when a kinase activity is under regulation. ...
Results: We used curated phosphoproteomic experiments and a gold standard dataset containing a total of 184 kinase-condition pairs where regulation is expected to occur to benchmark and compare different ...
Substrate-based kinase activity inference methods For each perturbation in the gold standard, we calculated the changes in kinase activities based on the quantitative phosphoproteomic profile and the set ...
doi:10.1093/bioinformatics/btx082
pmid:28200105
pmcid:PMC5870625
fatcat:wigi7rf6dnd7loedf3j32kc2km
KEA3: improved kinase enrichment analysis via data integration
2021
Nucleic Acids Research
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To benchmark the performance of KEA3, we examined whether KEA3 can predict the perturbed kinase from single-kinase perturbation followed by gene expression experiments, and phosphoproteomics data collected ...
Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. ...
KSEA is a web-based tool that uses known kinase-phosphosite relationships to compute a normalized score for each protein kinase based on the relative hyper-or hypo-phosphorylation of its substrates. ...
doi:10.1093/nar/gkab359
pmid:34019655
pmcid:PMC8265130
fatcat:gru3qfwaofbnvpd33jgy3nlh2e
Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources
2020
Clinical Proteomics
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phosphorylation sites in addition to the kinase that phosphorylates them, infer kinase activity, and predict the effect of mutations on kinase signaling. ...
Therefore, we put together a comprehensive collection of resources related to phosphoproteomics data interpretation, compared the use of tools with similar functions, and assessed the usability from the ...
Comparison of kinase activity tools The known or predicted kinases for phosphorylation sites can be used to infer kinase activity from global phosphoproteomic data. ...
doi:10.1186/s12014-020-09290-x
pmid:32676006
pmcid:PMC7353784
fatcat:46g4eyf64jez3n7m67dughs3ui
Phosphoproteomics-Based Profiling of Kinase Activities in Cancer Cells
[chapter]
2018
Msphere
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We then introduce different methods to infer kinase activities from phosphoproteomics data and these kinase-substrate relationships. ...
this chapter, we discuss the use of computational methods to predict kinase activity scores from MS-based phosphoproteomics data. ...
of kinase activity from phosphoproteomics data is related to the inference of transcription factor activity based on gene expression data. ...
doi:10.1007/978-1-4939-7493-1_6
pmid:29344887
pmcid:PMC6126574
fatcat:bojox67fvzh4po3cqoyooxxkfm
Phosphoproteomics-based Profiling of Kinase Activities in Cancer Cells
[article]
2016
bioRxiv
pre-print
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We then introduce different methods to infer kinase activities from phosphoproteomics data and these kinase-substrate relationships. ...
In this chapter, we discuss the use of computational methods to predict kinase activity scores from MS-based phosphoproteomics data. ...
of kinase activity from phosphoproteomics data is related to the inference of transcription factor activity based on gene expression data. ...
doi:10.1101/066019
fatcat:i2cnqalbtbh7tkvrchulavzo3q
Elucidating synergistic dependencies in lung adenocarcinoma by proteome-wide signaling-network analysis
2019
PLoS ONE
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To address this challenge, we introduce a novel algorithm for the systematic inference of protein kinase pathways, and applied it to published mass spectrometry-based phosphotyrosine profile data from ...
The resulting network includes 43 TKs and 415 inferred, LUAD-specific substrates, which were validated at >60% accuracy by SILAC assays, including "novel' substrates of the EGFR and c-MET TKs, which play ...
Discussion In this paper, we developed pARACNe to infer Tyrosine Kinase (TK) signaling network using published global phosphoproteomic data from lung cancer. ...
doi:10.1371/journal.pone.0208646
pmid:30615629
pmcid:PMC6322741
fatcat:73xsxhy35zhq7f2lkxakzibbly
FUNKI: Interactive functional footprint-based analysis of omics data
[article]
2021
arXiv
pre-print
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In particular, changes in omics can be used to estimate the activity of pathways, transcription factors and kinases based on known regulated targets, that we call footprints. ...
Motivation: Omics data, such as transcriptomics or phosphoproteomics, are broadly used to get a snap-shot of the molecular status of cells. ...
Instead of TF-target interactions, KinAct uses collections of kinase-substrate interactions via OmniPath (Türei et al., 2016) and phosphoproteomic data instead of transcriptomic data. ...
arXiv:2109.05796v1
fatcat:icaffyx7mjfaxbi75i3vune6lq
Phosphotyrosine-based phosphoproteomics for target identification and drug response prediction in AML cell lines
2020
Molecular & Cellular Proteomics
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The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidate for KI treatment, and efficacy of selected KIs was tested. ...
In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. ...
Kinase activation was inferred from total kinase phosphorylation and activation-loop phosphorylation and substrate driven analysis was done using known kinase-substrate relations and the motif-based kinase-substrate ...
doi:10.1074/mcp.ra119.001504
pmid:32102969
pmcid:PMC7196578
fatcat:umpjxso3gbakpkipdki5cha53q
Elucidating synergistic dependencies in lung adenocarcinoma by proteome-wide signaling-network analysis
[article]
2018
bioRxiv
pre-print
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To address this challenge, we present systematic, computational reconstruction of tyrosine kinase (TK) signal transduction pathways, based on mass spectrometry-based proteomics profiling of phosphotyrosine-enriched ...
The network represents 43 TKs and their predicted substrates, which were validated at >60% accuracy by SILAC assays, including "novel" substrates of the EGFR and c-MET TKs, which play a critical oncogenic ...
a phospho-isoform of a kinase and its enzymatic activity. 448 449 450Even though research has attempted to identify addiction points based on gene expression data 451 (74), predictions based on phosphoproteomic ...
doi:10.1101/289603
fatcat:nv7n6rionrdp3eqjcpw4jrpiby
An atlas of human kinase regulation
2016
Molecular Systems Biology
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Co-regulation along the conditions predicts kinase-complex and kinase-substrate associations. ...
Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. ...
Acknowledgements We thank all the groups involved in generating the phosphoproteomics data for their invaluable public resource. ...
doi:10.15252/msb.20167295
pmid:27909043
pmcid:PMC5199121
fatcat:mpxtoiiabjdh7ktgtvf7pmjdya
An Atlas of Human Kinase Regulation
[article]
2016
bioRxiv
pre-print
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Co-regulation along the conditions predicts kinase-complex and kinase-substrate associations. ...
This provides a global view of human phosphorylation-based signaling and the necessary context to better understand kinase driven decision-making. ...
Kinase activity validation using RPPA data We compared the predictions based on the collected quantitative phosphoproteomic data with the antibodybased kinase activities from a previous study (Hill et ...
doi:10.1101/067900
fatcat:qk65wcw2dnd4ri6jn5pidjxbhi
Phosphoproteomics by mass spectrometry: insights, implications, applications and limitations
2009
Espert Review of Proteomics
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Recent advances have allowed the global scope of phosphorylation to be addressed by mass spectrometry using phosphoproteomic approaches. ...
In this perspective we discuss four aspects of phosphoproteomics; namely insights and implications from recently published phosphoproteomic studies, and applications and limitations of current phosphoproteomic ...
U0126, a widely used inhibitor for Mek kinases was used to prevent activation of Erk and downstream kinases upon TCR stimulation. ...
doi:10.1586/epr.09.84
pmid:19929607
pmcid:PMC2931417
fatcat:zwieukyxnzay3ciapwrnrnut4q
CoPhosK: A Method for Comprehensive Kinase Substrate Annotation Using Co-phosphorylation Analysis
[article]
2018
bioRxiv
pre-print
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Through the mining of MS data for the collective dynamic signatures of the kinases' substrates, as revealed by correlation analysis of phosphopeptide intensity data, the tool infers KSAs in the data for ...
We benchmarked the tool against existing approaches for predicting KSAs that rely on static information (e.g. sequences, structures and interactions) using publically available MS data, including breast ...
To provide further guidance for benchmarking the method, we carried out simulations using synthetic data. ...
doi:10.1101/251009
fatcat:nfj4cs6idbfwxjmmvcjvovnd4q
Machine Learning of Global Phosphoproteomic Profiles Enables Discrimination of Direct versus Indirect Kinase Substrates
2017
Molecular & Cellular Proteomics
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Here, we describe a framework for assignment of direct in vivo kinase substrates using a combination of selective chemical inhibition, quantitative phosphoproteomics, and machine learning techniques. ...
Global phosphoproteome analysis of acute time-series demonstrated that dephosphorylation of direct kinase substrates occurs more rapidly compared with indirect substrates, both after inhibitor treatment ...
RESULTS
Inhibition of Cdc28-as Results in Phosphorylation and Dephosphorylation of a Large Number of Substrates-We used quantitative SILAC-based phosphoproteomics to study the global effect of inhibition ...
doi:10.1074/mcp.m116.066233
pmid:28265048
pmcid:PMC5417821
fatcat:bomk3sbdmrguzhefn6bbw6ppoq
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