Topology-enhanced molecular graph representation for anti-breast cancer drug selection

BACKGROUND: Breast cancer is currently one of the cancers with a higher mortality rate in the world. The biological research on anti-breast cancer drugs focuses on the activity of estrogen receptors alpha (ER[Formula: see text] ), the pharmacokinetic properties and the safety of the compounds, which, however, is an expensive and time-consuming process. Developments of deep learning bring potential to efficiently facilitate the candidate drug selection against breast cancer. METHODS: In this paper, we propose an Anti-Breast Cancer Drug selection method utilizing Gated Graph Neural Networks (ABCD-GGNN) to topologically enhance the molecular representation of candidate drugs. By constructing atom-level graphs through atomic descriptors for each distinct compound, ABCD-GGNN can topologically learn both the implicit structure and substructure characteristics of a candidate drug and then integrate the representation with explicit discrete molecular descriptors to generate a molecule-level representation. As a result, the representation of ABCD-GGNN can inductively predict the ER[Formula: see text] , the pharmacokinetic properties and the safety of each candidate drug. Finally, we design a ranking operator whose inputs are the predicted properties so as to statistically select the appropriate drugs against breast cancer. RESULTS: Extensive experiments conducted on our collected anti-breast cancer candidate drug dataset demonstrate that our proposed method outperform all the other representative methods in the tasks of predicting ER[Formula: see text] , and the pharmacokinetic properties and safety of the compounds. Extended result analysis demonstrates the efficiency and biological rationality of the operator we design to calculate the candidate drug ranking from the predicted properties. CONCLUSION: In this paper, we propose the ABCD-GGNN representation method to efficiently integrate the topological structure and substructure features of the molecules with the discrete molecular descriptors. With a ranking operator applied, the predicted properties efficiently facilitate the candidate drug selection against breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04913-6.