Long, Y., Wu, M., Liu, Y., Zheng, J., Kwoh, C. K., Luo, J., &amp; Li, X. (2021). Graph contextualized attention network for predicting synthetic lethality in human cancers. Bioinformatics, 37(16), 2432–2440. doi:10.1093/bioinformatics/btab110
Synthetic Lethality (SL) plays an increasingly critical role in the targeted anticancer therapeutics. In addition, identifying SL interactions can create opportunities to selectively kill cancer cells without harming normal cells. Given the high cost of wet-lab experiments, in silico prediction of SL interactions as an alternative can be a rapid and cost-effective way to guide the experimental screening of candidate SL pairs. Several matrix factorization-based methods have recently been proposed for human SL prediction. However, they are limited in capturing the dependencies of neighbors. In addition, it is also highly challenging to make accurate predictions for new genes without any known SL partners.
In this work, we propose a novel graph contextualized attention network named GCATSL to learn gene representations for SL prediction. First, we leverage different data sources to construct multiple feature graphs for genes, which serve as the feature inputs for our GCATSL method. Second, for each feature graph, we design node-level attention mechanism to effectively capture the importance of local and global neighbors and learn local and global representations for the nodes, respectively. We further exploit multi-layer perceptron (MLP) to aggregate the original features with the local and global representations and then derive the feature-specific representations. Third, to derive the final representations, we design feature-level attention to integrate feature-specific representations by taking the importance of different feature graphs into account. Extensive experimental results on three datasets under different settings demonstrated that our GCATSL model outperforms 14 state-of-the-art methods consistently. In addition, case studies further validated the effectiveness of our proposed model in identifying novel SL pairs.
Python codes and dataset are freely available on GitHub (https://github.com/longyahui/GCATSL) and Zenodo (https://zenodo.org/record/4522679) under the MIT license.
Supplementary data are available at Bioinformatics online.
This work was supported by the National Natural Science Foundation
of China , the Major Program of National Natural Science
Foundation of China  and the Chinese Scholarship Council
This is a pre-copyedited, author-produced version of an article accepted for publication in Bioinformatics following peer review. The version of record Yahui Long, Min Wu, Yong Liu, Jie Zheng, Chee Keong Kwoh, Jiawei Luo, Xiaoli Li, Graph contextualized attention network for predicting synthetic lethality in human cancers, Bioinformatics, Volume 37, Issue 16, 15 August 2021, Pages 2432–2440, https://doi.org/10.1093/bioinformatics/btab110 is available online at: http://dx.doi.org/10.1093/bioinformatics/btab110.