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Table 1 Selection of published kinase activity analysis pipelines using phosphoproteomics data

From: Inference of kinase-signaling networks in human myeloid cell line models by Phosphoproteomics using kinase activity enrichment analysis (KAEA)

Software Method Statistic Database Input Visualization
Kinase-Set Enrichment Analysis (KSEA) [19, 20] Calculate the ratio of the means of the phosphorylated peptide abundances in the substrate groups relative to their abundances in the whole data set z-score PhosphoSitePlus + NetworKIN Pre-processed comma-separated file with columns of proteins, genes, peptides, phosphosites, p-values and Fold changes KSEA Shiny App
Kinase-Enrichment Analysis (KEA) [21] Calculate significant deviations from the expected value which is the cardinality of the set of substrates that are targeted by specific kinases divided by the total number of substrates in the background dataset Fisher’s exact test NetworKIN + Phospho.ELM + MINT + HPRD + Swiss-Prot + PhosphoPoint +Manual annotations List of gene symbols Web tool
Kinase Perturbation Analysis (KinasePA) [22] In-house directional hypothesis testing framework for pathway analysis Stouffer’s statistics (z-score) PhosphoSitePlus +Phospho.ELM Pre-processed comma-separated file with columns of phosphosites and fold changes ShinyApp R package
Knowledge-based CLUster Evaluation (CLUE) [23] Estimate the optimal number of clusters in dataset using K-means based clustering and then identifying the enriched kinases in each cluster Fisher’s exact test PhosphoSitePlus Time-course data set with columns of phosphosites and fold changes at time points R package
Inference of kinase activities from phosphoproteomics (IKAP) [24] Non-linear optimization routine to minimize the cost function that relates kinase activities and affinities to phosphosite measurements PhosphoSitePlus Data set with columns of protein or gene names, the sequences of the measured peptides and data values Matlab
Integrative Inferred Kinase Activity (INKA) [25] Inference from single biological samples, combining both kinase- and substrate-centric evidence metrics INKA score PhosphoSitePlus + NetworKIN MaxQuant output files Web tool
Kinase activity ranking using phosphoproteomics (KARP) [26] Model the contribution of kinases to cell viability by the net activity of a kinase which is calculated as the sum of intensities of its known substrates relative to the sum of intensities of all phosphorylation sites in the studied dataset. K-score PhosphoSitePlus MaxQuant output files n.a.