MULGA, a unified multi-view graph autoencoder-based approach for identifying drug-protein interaction and drug repositioning

Jiani Ma, Chen Li, Yiwen Zhang, Zhikang Wang, Shanshan Li, Yuming Guo, Lin Zhang, Hui Liu, Xin Gao, Jiangning Song

Research output: Contribution to journalArticlepeer-review


Motivation: Identifying drug-protein interactions (DPIs) is a critical step in drug repositioning, which allows reuse of approved drugs that may be effective for treating a different disease and thereby alleviates the challenges of new drug development. Despite the fact that a great variety of computational approaches for DPI prediction have been proposed, key challenges, such as extendable and unbiased similarity calculation, heterogeneous information utilization and reliable negative sample selection, remain to be addressed. Results: To address these issues, we propose a novel, unified multi-view graph autoencoder framework, termed MULGA, for both DPI and drug repositioning predictions. MULGA is featured by: (i) a multi-view learning technique to effectively learn authentic drug affinity and target affinity matrices; (ii) a graph autoencoder to infer missing DPI interactions; and (iii) a new “guilty-by-association”-based negative sampling approach for selecting highly reliable non-DPIs. Benchmark experiments demonstrate that MULGA outperforms state-of-the-art methods in DPI prediction and the ablation studies verify the effectiveness of each proposed component. Importantly, we highlight the top drugs shortlisted by MULGA that target the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), offering additional insights into and potentially useful treatment option for COVID-19. Together with the availability of datasets and source codes, we envision that MULGA can be explored as a useful tool for DPI prediction and drug repositioning.
Original languageEnglish (US)
StatePublished - Aug 23 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-08-31
Acknowledgements: This work was supported by grants from the National Science Foundation of China (No. 61971422) and a Major Inter-Disciplinary Research Grant awarded by Monash University.

ASJC Scopus subject areas

  • Biochemistry
  • Computational Theory and Mathematics
  • Computational Mathematics
  • Molecular Biology
  • Statistics and Probability
  • Computer Science Applications


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