# A Knowledge Graph Embedding Approach for Polypharmacy Side Effects Prediction
## 5 Conclusions and Discussion  
We proposed a unified embedding approach that made it possible to incorporate labeled single drug data, labeled multidrug data, nodes connectivity shown in the knowledge graph, and unlabeled virtual multidrug data into embedding space. In previous studies, the polypharmacy side effects prediction model did not learn relationships between single drug characteristics and its labels. In this study, however, we applied these relationships to learning models via the unified embedding approach and succeeded in improving the prediction performance. In addition, learning the relationships between multidrug and all graph nodes, not just between multidrug and neighboring nodes, appears to have the effect of reducing overfitting in the predictive models. This effect was further enhanced by \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Side Effect ID** & **Significant GO Term** & **GO ID** & **Overlap \({}^{*}\)** & **Adjusted** \(\mathbf{p}\)-Value** & **Related Literatures and Notes** \\ \hline Hyperparathyroidism & Histone ubiquitination & GO0016574 & 7/21 & 0.009554 & Hyperparathyroidism is related to histone [42, 43]. \\ \hline Hyperpigmentation & Histone H2B ubiquitination & GO0033523 & 5/10 & 0.003118 & Pigmentation is related to histone H2B in Drosophila [44, 45]. \\ \hline Hypoglycaemia neonatal & Protein serine/threonine kinase activator activity & GO0043539 & 6/37 & 0.001837 & Neonatal hypoglycaemia is related to serine/threonine kinase [46]. \\ \hline Ingrowing nail & Regulation of amyloid precursor protein biosynthetic process & GO0042984 & 6/11 & 0.003511 & Nail growing is related to amyloid [47, 48, 49, 50]. \\ \hline Motor retardation & Platelet aggregation & GO0070527 & 8/36 & 0.004725 & Psychomotor activity is related to platelet [51, 52]. \\ \hline Myocarditis & Cyclin/CDK positive transcription elongation factor complex & GO0008024 & 4/6 & 0.001296 & Myocardial is strongly related to cyclin/CDK [53]. \\ \hline Ovarian cancer & Ubiquitin binding & GO0043130 & 8/73 & 0.004612 & Ovarian cancer is related to ubiquitin [54, 55]. \\ \hline Pigmentation disorder & Ubiquitin binding & GO0043130 & 8/73 & 0.006731 & Pigmentation is related to ubiquitin [56]. \\ \hline Pleural fibrosis & Quinone biosynthetic process & GO1901663 & 5/14 & 0.009926 & Fibrosis of liver and kidney is related to pyrrolouionine-quinone [57, 58]. \\ \hline Premature menopause & Intermediate & GO0045109 & 8/18 & 0.005884 & Premature menopause is strongly related to actin filament [59, 60]. \\ \hline Soft tissue infection & Protein K63-linked deubiquitination & GO0070536 & 6/32 & 0.00143 & K63-linked deubiquitination is related to antiviral response [61, 62]. \\ \hline Synovitis & Intraciliary transport involved in cilium assembly & GO0035735 & 10/40 & 0.000563 & Synovitis is related to cilia [63, 64]. \\ \hline Colitis pseudommenbrans & DNA-templated transcription, elongation & GO0006354 & 10/69 & 0.004319 & \\ \hline Dysphemia & Intraciliary transport involved in cilium assembly & GO0035735 & 11/40 & 0.00759 & \\ \hline Flashing lights & Histone monobiquitination & GO0010390 & 8/24 & 0.005066 & \\ \hline Furuncle & Coenzyme A metabolic process & GO0015936 & 6/14 & 0.005619 & Not found related Literatures \\ \hline Myasthenemia gravis & Histone ubiquitination & GO0016574 & 9/21 & 0.0000616 & \\ \hline Seborrhoeic keratosis & Prenyltransferase activity & GO0004659 & 6/9 & 0.008161 & \\ \hline Sinus headache & tRNA wobble base modification & GO0002097 & 7/14 & 0.00292 & \\ \hline Trigger finger & Positive regulation of protein export from nucleus & GO0046827 & 7/15 & 0.003106 & \\ \hline \hline \end{tabular}
\end{table} 
Table 6: _Cont._regularizing the models using virtual multidrug data. In particular, the application of this embedding approach under multidrug inputs, including new drugs not used in existing drug combinations, clearly improved the generalizability when virtual multidrug data are used together with single drug label data.