For this case study, we trained a classifier to predict known interactions between kinases and their substrates, and then predicted kinases for proteins that have phosphosites with unknown regulatory kinase. The classifier performed modestly in cross-validation with an area under the receiver operating characteristic curve of 0.88, F1-score of 0.23, and Matthew’s correlation coefficient of 0.22. Methods and results for this machine learning case study are described in detail in the Harmonizome publication.
Each row in the results table provides the gene symbol of a kinase (Kinase column), provides the gene symbol of a phosphoprotein (Substrate column), provides the predicted probability that the Kinase phosphorylates the protein (Probability column), indicates whether the phosphorylation reaction is known (Known column), indicates whether the pair was used as an example for training the classifier (Training column), and provides the predicted false discovery rate if all predictions with better or equivalent probability were tested (FDR column).
The table below shows predictions with probabilities greater than or equal to 0.5. To download the full table:
Kinase | Substrate | Probability | Known | Training | FDR |
---|---|---|---|---|---|
CDK1 | MELK | 0.76 | false | true | 1.0 |
CDK1 | DLGAP5 | 0.72 | true | true | 0.5 |
PRKCD | LRRC7 | 0.71 | false | true | 0.67 |
CDK1 | CENPF | 0.71 | false | true | 0.75 |
CDK2 | E2F1 | 0.7 | true | true | 0.6 |
CDK1 | CDC6 | 0.69 | false | true | 0.67 |
CDK1 | NUSAP1 | 0.68 | true | true | 0.5 |
CDK1 | TPX2 | 0.68 | true | true | 0.57 |
CAMK2A | MYOM3 | 0.68 | false | false | 0.62 |
MAPK1 | FOS | 0.67 | true | true | 0.44 |
CDK1 | RRM2 | 0.67 | true | true | 0.4 |
CDK1 | AURKA | 0.67 | true | true | 0.36 |
CDK1 | CCNA2 | 0.66 | false | true | 0.44 |
CDK1 | TTK | 0.66 | false | true | 0.41 |
CDK1 | CDC20 | 0.66 | true | true | 0.38 |
CDK1 | CDK1 | 0.66 | true | true | 0.4 |
CDK2 | MCM3 | 0.66 | true | true | 0.43 |
CDK1 | ASPM | 0.66 | false | true | 0.46 |
CDK1 | CDT1 | 0.66 | false | true | 0.42 |
CDK2 | TOP2A | 0.65 | false | true | 0.45 |
CDK1 | DTL | 0.65 | true | true | 0.43 |
CDK2 | TK1 | 0.65 | true | true | 0.45 |
CAMK2A | HECW1 | 0.65 | false | false | 0.47 |
CDK1 | AURKB | 0.65 | false | true | 0.47 |
PLK1 | CENPF | 0.64 | false | true | 0.52 |
CDK1 | MCM6 | 0.64 | false | false | 0.51 |
MAPK3 | EGR1 | 0.64 | false | true | 0.5 |
CDK1 | CENPA | 0.64 | true | true | 0.48 |
PRKCD | CRHR1 | 0.64 | false | true | 0.52 |
CDK2 | MYC | 0.64 | true | true | 0.5 |
SGK1 | LRRC7 | 0.64 | false | true | 0.5 |
CDK1 | PLK1 | 0.64 | false | true | 0.48 |
CDK2 | CCND1 | 0.64 | true | true | 0.46 |
SGK1 | CRHR1 | 0.64 | false | true | 0.48 |
CDK1 | KIAA0101 | 0.63 | false | false | 0.48 |
MAPK1 | JUN | 0.63 | true | true | 0.47 |
CDK1 | E2F1 | 0.63 | true | true | 0.49 |
CAMK2A | HPSE2 | 0.63 | false | false | 0.49 |
CDK2 | MYBL2 | 0.63 | true | true | 0.5 |
LCK | CD6 | 0.63 | false | true | 0.51 |
CDK1 | MAD2L1 | 0.63 | false | true | 0.5 |
CDK1 | STMN1 | 0.63 | true | true | 0.48 |
CDK1 | BUB1B | 0.63 | true | true | 0.5 |
CDK1 | KIFC1 | 0.62 | false | true | 0.5 |
CDK1 | GTSE1 | 0.62 | false | true | 0.49 |
CDK1 | H2AFZ | 0.62 | false | false | 0.49 |
CDK1 | CCNB2 | 0.62 | false | false | 0.48 |
CDK2 | MCM7 | 0.61 | true | true | 0.5 |
LCK | IL16 | 0.61 | false | true | 0.51 |
MAPK14 | CDKN1A | 0.61 | true | true | 0.5 |
MAPK1 | EGR1 | 0.61 | false | true | 0.51 |
CDK1 | UBE2C | 0.61 | false | false | 0.51 |
CDK2 | RFC3 | 0.6 | false | false | 0.51 |
CDK2 | MCM6 | 0.6 | false | false | 0.51 |
CDK1 | PRC1 | 0.6 | true | true | 0.51 |
CDK1 | MCM2 | 0.6 | false | true | 0.52 |
PLK1 | CDK1 | 0.6 | false | true | 0.51 |
CDK2 | BUB1 | 0.6 | false | true | 0.5 |
CDK1 | KIF23 | 0.6 | false | true | 0.49 |
CDK2 | MCM2 | 0.6 | true | true | 0.48 |
MAPK14 | JUN | 0.6 | true | true | 0.49 |
CDK1 | CENPU | 0.59 | false | true | 0.51 |
MAPK1 | JUNB | 0.59 | true | true | 0.5 |
PLK1 | TTK | 0.59 | false | true | 0.51 |
CDK1 | LMNB1 | 0.59 | true | true | 0.5 |
FYN | CD6 | 0.58 | false | true | 0.52 |
CDK2 | STMN1 | 0.58 | true | true | 0.52 |
CDK2 | TFDP1 | 0.58 | false | true | 0.53 |
CDK2 | CDC6 | 0.58 | true | true | 0.52 |
CDK1 | ATAD2 | 0.58 | false | true | 0.53 |
CDK1 | SMC4 | 0.58 | false | true | 0.52 |
MAPK1 | CCND1 | 0.57 | false | true | 0.53 |
MAPK1 | CDKN1A | 0.57 | true | true | 0.52 |
PRKACA | LRRC7 | 0.57 | false | true | 0.52 |
CDK1 | CCNB1 | 0.57 | true | true | 0.51 |
CDK2 | PCNA | 0.57 | false | true | 0.52 |
CDK2 | CDT1 | 0.57 | true | true | 0.52 |
CDK1 | CCND1 | 0.57 | false | true | 0.53 |
CDK1 | MCM7 | 0.57 | true | true | 0.52 |
CDK2 | SIN3A | 0.57 | true | true | 0.52 |
PLK1 | NCAPH | 0.57 | false | true | 0.53 |
CDK1 | RACGAP1 | 0.56 | true | true | 0.52 |
CSNK2A2 | CCND1 | 0.56 | false | true | 0.53 |
MAPK14 | DUSP1 | 0.56 | false | true | 0.52 |
CDK1 | GINS2 | 0.56 | false | true | 0.51 |
MAPK14 | MYC | 0.56 | true | true | 0.51 |
CSNK2A1 | CCND1 | 0.56 | false | true | 0.51 |
CDK2 | BRCA1 | 0.56 | true | true | 0.51 |
CDK1 | MYBL2 | 0.56 | true | true | 0.51 |
CDK1 | MCM4 | 0.55 | true | true | 0.52 |
CDK2 | CHEK1 | 0.55 | true | true | 0.52 |
LCK | LILRB2 | 0.55 | false | false | 0.51 |
GSK3B | TP53 | 0.55 | true | true | 0.51 |
CDK1 | MKI67 | 0.55 | true | true | 0.51 |
CSNK2A2 | CCNB1 | 0.55 | false | true | 0.51 |
CSNK2A1 | JUNB | 0.55 | false | true | 0.53 |
PRKACA | CRYBG3 | 0.55 | false | false | 0.52 |
MAPK1 | DUSP1 | 0.55 | true | true | 0.51 |
CDK1 | KIF11 | 0.55 | true | true | 0.51 |
MAPK14 | GADD45B | 0.55 | false | true | 0.51 |
CDK1 | HMGB2 | 0.55 | false | true | 0.52 |
CDK1 | NCAPH | 0.55 | false | true | 0.52 |
FYN | TIGIT | 0.55 | false | false | 0.52 |
GSK3B | JUN | 0.54 | true | true | 0.52 |
PRKACA | KRT72 | 0.54 | false | false | 0.52 |
CDK2 | CDKN1A | 0.54 | true | true | 0.53 |
CDK2 | GMNN | 0.54 | false | true | 0.53 |
CSNK2A1 | FOS | 0.54 | false | true | 0.53 |
MAPK14 | TP53 | 0.54 | true | true | 0.52 |
CDK1 | NEK2 | 0.54 | false | true | 0.53 |
PRKCA | PRH2 | 0.54 | false | true | 0.52 |
CDK2 | PLK4 | 0.54 | false | true | 0.52 |
MAPK14 | MDM2 | 0.53 | false | true | 0.52 |
CDK1 | KPNA2 | 0.53 | false | true | 0.52 |
SGK1 | KIAA1211 | 0.53 | false | false | 0.52 |
CDK1 | FOS | 0.53 | false | true | 0.52 |
CDK1 | FEN1 | 0.53 | true | true | 0.51 |
CDK1 | ANLN | 0.53 | true | true | 0.52 |
FYN | CD3D | 0.53 | false | true | 0.52 |
CDK1 | SKP2 | 0.53 | false | true | 0.52 |
CDK1 | CHEK1 | 0.53 | true | true | 0.51 |
CDK1 | ZNF148 | 0.53 | false | true | 0.52 |
CSNK2A1 | TP53 | 0.53 | true | true | 0.51 |
PRKCA | KIR3DL1 | 0.53 | true | true | 0.52 |
CAMK2A | PARK2 | 0.53 | false | true | 0.52 |
PRKCA | KRT72 | 0.53 | false | false | 0.52 |
MAPK1 | GADD45B | 0.53 | false | true | 0.52 |
MAPK14 | EGR1 | 0.53 | false | true | 0.53 |
CDK1 | CDC7 | 0.53 | true | true | 0.52 |
CSNK2A1 | MYC | 0.53 | true | true | 0.52 |
MAPK3 | FOS | 0.53 | true | true | 0.51 |
CDK2 | AURKB | 0.52 | false | true | 0.54 |
CDK2 | CCNT1 | 0.52 | false | true | 0.55 |
GSK3B | CCND1 | 0.52 | true | true | 0.55 |
CDK2 | CDC25B | 0.52 | false | true | 0.55 |
PRKCD | KIAA1211 | 0.52 | false | false | 0.55 |
CDK1 | CDKN3 | 0.52 | false | false | 0.55 |
SGK1 | KRT72 | 0.52 | false | false | 0.55 |
CDK1 | RFC3 | 0.52 | false | false | 0.55 |
CDK2 | TYMS | 0.52 | false | true | 0.55 |
GSK3B | RPTOR | 0.52 | true | true | 0.55 |
PRKACA | KIR3DL1 | 0.52 | false | true | 0.54 |
CDK2 | EHMT2 | 0.52 | false | true | 0.54 |
CDK2 | SKP2 | 0.52 | true | true | 0.52 |
PRKCD | CRYBG3 | 0.52 | false | false | 0.52 |
CDK1 | KIF4A | 0.52 | false | true | 0.52 |
CDK1 | ZWINT | 0.52 | false | false | 0.52 |
PRKCA | MYH8 | 0.52 | false | false | 0.52 |
CSNK2A1 | EGFR | 0.52 | true | true | 0.52 |
AKT1 | TP53 | 0.52 | false | true | 0.52 |
SRC | CRHR1 | 0.52 | false | true | 0.53 |
MAPK1 | GADD45A | 0.52 | false | true | 0.53 |
PRKCA | CRHR1 | 0.52 | false | true | 0.53 |
CDK2 | CCNE2 | 0.51 | false | true | 0.54 |
CDK2 | FN1 | 0.51 | false | true | 0.55 |
PLK1 | BUB1 | 0.51 | true | true | 0.54 |
CDK2 | CDC25A | 0.51 | true | true | 0.54 |
PRKCA | CDKN1A | 0.51 | true | true | 0.53 |
PRKCA | KRT18 | 0.51 | true | true | 0.53 |
PRKCA | IL16 | 0.51 | false | true | 0.53 |
GSK3B | MCM3 | 0.51 | false | true | 0.53 |
CDK1 | NCAPG | 0.51 | true | true | 0.54 |
CAMK2A | ZNF229 | 0.51 | false | false | 0.54 |
PRKCD | KRT72 | 0.51 | false | false | 0.55 |
CDK1 | CCNE1 | 0.51 | false | true | 0.55 |
CDK2 | CDC7 | 0.51 | true | true | 0.55 |
MAPK1 | BCL2 | 0.51 | true | true | 0.54 |
CDK1 | RAD51 | 0.51 | false | true | 0.54 |
PLK1 | TOP2A | 0.51 | true | true | 0.54 |
CDK2 | SIRT6 | 0.51 | false | false | 0.54 |
PRKACA | SLC14A2 | 0.51 | false | false | 0.54 |
CDK1 | ASF1B | 0.5 | false | true | 0.53 |
CDK1 | CDC45 | 0.5 | false | false | 0.53 |
CDK2 | ZNF485 | 0.5 | false | false | 0.53 |
CDK1 | CDC25A | 0.5 | true | true | 0.53 |
CDK4 | SETD2 | 0.5 | false | true | 0.53 |
MAPK9 | CELF1 | 0.5 | false | true | 0.53 |
CDK1 | TUBG1 | 0.5 | false | true | 0.54 |
MAPK3 | JUN | 0.5 | true | true | 0.53 |
MAPK14 | FOS | 0.5 | true | true | 0.53 |
CDK2 | EGFR | 0.5 | true | true | 0.53 |
GSK3B | SPEN | 0.5 | true | true | 0.53 |
MAPK14 | BRCA1 | 0.5 | false | true | 0.53 |
CDK2 | CENPF | 0.5 | true | true | 0.53 |
CSNK2A1 | RB1 | 0.5 | false | true | 0.54 |
GSK3B | NOTCH2 | 0.5 | true | true | 0.53 |
CDK2 | CDK1 | 0.5 | false | true | 0.53 |
PLK1 | DTL | 0.5 | false | true | 0.54 |
CDK1 | CEP55 | 0.5 | true | true | 0.53 |
CSNK2A1 | BTG2 | 0.5 | false | true | 0.54 |
LYN | CD79A | 0.5 | true | true | 0.53 |
PRKCA | CLDN18 | 0.5 | false | false | 0.53 |
CDK2 | BCL2 | 0.5 | true | true | 0.53 |
CDK1 | CHAF1A | 0.5 | false | true | 0.53 |