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