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

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.