For this case study, we trained a classifier to predict known interactions between G protein-coupled receptors (GPCRs) and protein-derived ligands, and then predicted ligands for orphan GPRCs. The classifier performed well in cross-validation with an area under the receiver operating characteristic curve of 0.91, F1-score of 0.59, and Matthew’s correlation coefficient of 0.59. 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 GPCR (GPCR column), provides the gene symbol of a candidate protein-derived ligand (Ligand column), provides the predicted probability that the candidate ligand binds to the GPCR (Probability column), indicates whether pair is known to interact (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:
GPCR | Ligand | Probability | Known | Training | FDR |
---|---|---|---|---|---|
CCR5 | CCL7 | 0.92 | true | true | 0.0 |
CXCR2 | CXCL1 | 0.89 | true | true | 0.0 |
LGR4 | RSPO4 | 0.89 | true | true | 0.0 |
CCR5 | CCL8 | 0.88 | true | true | 0.0 |
CXCR2 | CXCL6 | 0.87 | true | true | 0.0 |
LGR4 | RSPO1 | 0.86 | true | true | 0.0 |
NPY5R | NPY | 0.8 | true | true | 0.0 |
LGR4 | RSPO2 | 0.8 | true | true | 0.0 |
NPY5R | PYY | 0.79 | true | true | 0.08 |
LGR5 | RSPO4 | 0.79 | true | true | 0.08 |
RXFP2 | INS | 0.79 | false | false | 0.09 |
CCR1 | CCL11 | 0.79 | false | true | 0.09 |
LGR6 | RSPO4 | 0.79 | true | true | 0.0 |
CCR2 | CCL7 | 0.79 | true | true | 0.0 |
RXFP2 | IGF2 | 0.78 | false | false | 0.07 |
RXFP2 | IGF1 | 0.77 | false | false | 0.07 |
CXCR2 | PF4V1 | 0.77 | false | false | 0.07 |
CCR3 | CCL7 | 0.77 | true | true | 0.07 |
LGR5 | RSPO1 | 0.76 | true | true | 0.07 |
CXCR2 | CXCL5 | 0.76 | true | true | 0.06 |
CCR5 | CCL13 | 0.76 | true | true | 0.06 |
RXFP1 | INS | 0.76 | false | false | 0.06 |
RXFP1 | RLN1 | 0.76 | true | true | 0.06 |
RXFP2 | RLN1 | 0.75 | true | true | 0.05 |
CCR3 | CCL8 | 0.75 | true | true | 0.05 |
RXFP1 | IGF1 | 0.74 | false | false | 0.05 |
CCR1 | CCL5 | 0.74 | true | true | 0.05 |
CXCR2 | PF4 | 0.74 | false | false | 0.05 |
NPY1R | PYY | 0.73 | true | true | 0.05 |
FZD6 | WNT3 | 0.73 | false | false | 0.04 |
NPY1R | NPY | 0.73 | true | true | 0.04 |
CCR1 | CCL8 | 0.73 | true | true | 0.04 |
FZD6 | WNT5A | 0.72 | true | true | 0.1 |
CCR5 | CCL11 | 0.72 | true | true | 0.11 |
RXFP1 | IGF2 | 0.72 | false | false | 0.11 |
AVPR2 | OXT | 0.72 | true | true | 0.11 |
CCR1 | CCL16 | 0.72 | false | true | 0.12 |
CCR1 | CCL2 | 0.72 | false | true | 0.08 |
CCR2 | CCL5 | 0.71 | false | true | 0.12 |
AVPR1B | OXT | 0.71 | true | true | 0.09 |
TACR1 | TAC3 | 0.71 | true | true | 0.09 |
LGR5 | RSPO2 | 0.71 | true | true | 0.1 |
CCR1 | CCL7 | 0.71 | true | true | 0.1 |
SSTR4 | CORT | 0.7 | true | true | 0.11 |
LGR4 | RSPO3 | 0.7 | true | true | 0.11 |
CCR1 | CCL13 | 0.69 | true | true | 0.09 |
CCR5 | CCL5 | 0.69 | true | true | 0.09 |
SSTR1 | SST | 0.69 | true | true | 0.1 |
AVPR1A | AVP | 0.69 | true | true | 0.1 |
FZD6 | WNT4 | 0.69 | true | true | 0.1 |
VIPR1 | VIP | 0.69 | true | true | 0.1 |
SSTR1 | CORT | 0.69 | true | true | 0.11 |
AVPR1A | OXT | 0.69 | true | true | 0.11 |
CCR2 | CCL8 | 0.68 | true | true | 0.09 |
NPY2R | PPY | 0.68 | false | true | 0.11 |
CCR3 | CCL3 | 0.67 | false | true | 0.12 |
FZD6 | WNT3A | 0.67 | true | true | 0.1 |
MC4R | ASIP | 0.67 | true | true | 0.1 |
CXCR3 | CXCL9 | 0.67 | true | true | 0.11 |
RXFP2 | RLN3 | 0.66 | true | true | 0.14 |
CCR5 | CCL23 | 0.66 | false | true | 0.14 |
SSTR5 | SST | 0.66 | true | true | 0.13 |
SSTR5 | CORT | 0.66 | true | true | 0.13 |
CCR5 | CCL15 | 0.66 | false | true | 0.13 |
CXCR1 | CXCL8 | 0.66 | true | true | 0.11 |
CXCR2 | CXCL8 | 0.66 | true | true | 0.12 |
LGR5 | RSPO3 | 0.66 | true | true | 0.12 |
VIPR1 | GIP | 0.65 | false | true | 0.15 |
VIPR1 | SCT | 0.65 | true | true | 0.15 |
CCR5 | CCL3 | 0.64 | true | true | 0.15 |
SSTR4 | SST | 0.63 | true | true | 0.15 |
VIPR1 | GCG | 0.63 | false | true | 0.16 |
OXTR | OXT | 0.63 | true | true | 0.16 |
CXCR2 | CXCL3 | 0.62 | true | true | 0.15 |
LGR6 | RSPO1 | 0.62 | true | true | 0.15 |
CCR2 | CCL13 | 0.62 | true | true | 0.15 |
CXCR2 | YARS | 0.62 | false | true | 0.16 |
CXCR3 | CXCL10 | 0.61 | true | true | 0.15 |
AVPR1B | AVP | 0.61 | true | true | 0.15 |
AVPR2 | AVP | 0.61 | true | true | 0.16 |
FPR3 | ANXA1 | 0.61 | true | true | 0.16 |
OPRL1 | POMC | 0.6 | false | true | 0.16 |
SSTR2 | SST | 0.6 | true | true | 0.16 |
VIPR2 | SCT | 0.6 | true | true | 0.16 |
CCR5 | CCL2 | 0.6 | true | true | 0.16 |
CCR3 | CCL16 | 0.6 | false | true | 0.17 |
MC3R | ASIP | 0.6 | true | true | 0.17 |
CCR1 | CCL3 | 0.59 | true | true | 0.16 |
NPY2R | NPY | 0.59 | true | true | 0.16 |
VIPR2 | GCG | 0.58 | false | true | 0.16 |
MC5R | ASIP | 0.58 | true | true | 0.16 |
CCR2 | CCL11 | 0.58 | true | true | 0.15 |
RXFP1 | RLN3 | 0.58 | true | true | 0.15 |
OPRD1 | PDYN | 0.58 | true | true | 0.15 |
CCR3 | CCL13 | 0.58 | true | true | 0.16 |
SSTR3 | CORT | 0.58 | true | true | 0.16 |
SSTR2 | CORT | 0.58 | true | true | 0.16 |
OPRK1 | PDYN | 0.57 | true | true | 0.16 |
CXCR3 | CCL8 | 0.57 | false | true | 0.16 |
CCR2 | CCL2 | 0.57 | true | true | 0.15 |
NPY5R | PPY | 0.57 | true | true | 0.16 |
TACR3 | TAC3 | 0.57 | true | true | 0.16 |
NPY2R | PYY | 0.56 | true | true | 0.16 |
MC5R | AGRP | 0.56 | true | true | 0.16 |
TACR2 | TAC3 | 0.56 | true | true | 0.16 |
NPY1R | PPY | 0.56 | true | true | 0.17 |
ADCYAP1R1 | GCG | 0.56 | false | true | 0.17 |
CCR3 | CCL11 | 0.56 | true | true | 0.16 |
RXFP2 | INSL5 | 0.55 | false | true | 0.17 |
LGR6 | RSPO2 | 0.55 | true | true | 0.17 |
SSTR3 | SST | 0.55 | true | true | 0.17 |
OPRM1 | PDYN | 0.55 | true | true | 0.17 |
VIPR2 | VIP | 0.54 | true | true | 0.16 |
RXFP3 | IGF2 | 0.54 | false | false | 0.16 |
CCR1 | CCL18 | 0.54 | false | false | 0.16 |
NPBWR1 | NPW | 0.54 | true | true | 0.16 |
CXCR2 | PPBP | 0.54 | true | true | 0.16 |
OPRK1 | PENK | 0.53 | true | true | 0.18 |
LGR6 | RSPO3 | 0.53 | true | true | 0.18 |
CXCR1 | PPBP | 0.53 | false | true | 0.18 |
MRGPRX2 | AGT | 0.53 | false | true | 0.17 |
NPBWR1 | NPB | 0.53 | true | true | 0.17 |
FPR3 | CAMP | 0.53 | false | true | 0.17 |
CCR3 | CCL2 | 0.53 | true | true | 0.16 |
RXFP3 | INS | 0.53 | false | false | 0.16 |
OPRD1 | PENK | 0.52 | true | true | 0.19 |
CCR2 | CCL3 | 0.52 | false | true | 0.19 |
CCR5 | CCL18 | 0.52 | false | false | 0.19 |
GLP1R | SCT | 0.52 | false | true | 0.18 |
CXCR1 | PF4V1 | 0.52 | false | false | 0.18 |
CCR2 | CCL14 | 0.51 | false | true | 0.19 |
ADCYAP1R1 | VIP | 0.51 | true | true | 0.18 |
CCR5 | CCL14 | 0.51 | true | true | 0.18 |
MC4R | AGRP | 0.51 | true | true | 0.19 |
MC3R | POMC | 0.51 | true | true | 0.19 |
OPRM1 | PENK | 0.5 | true | true | 0.19 |
OXTR | AVP | 0.5 | true | true | 0.19 |
CXCR3 | CCL7 | 0.5 | true | true | 0.19 |