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Prediction of circRNA-drug sensitivity using random auto-encoders and multi-layer heterogeneous graph transformers

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Abstract

A growing evidence has demonstrated that the expression of circRNAs have significant impact on cell sensitivity to drugs, thereby affecting drug efficacy. Several computational methods have been developed to identify potential circRNA-drug sensitivity associations based on graph auto-encoder and multi-modal information of circRNA and drugs. However, multi-modal information may still lead to a local embedding representation space. And the graph auto-encoder is easy to neglect the global information of the whole graph. Thus, the predictive performance of existing methods is still not satisfactory and needs improvement. In this study, we introduce a model named MHGTCDA for forecasting potential circRNA-drug sensitivity associations using adaptive random auto-encoders (RAEs) and multi-layer Heterogeneous Graph Transformers (MHGT). Firstly, random auto-encoders are used to encode the circRNAs and drugs, respectively. Secondly, MHGT framework is used to obtain context representation of the nodes, which directly utilizes the edge information of the bipartite graph composed of circRNA-drug pairs, thereby reducing information loss. Then, the concatenated embedding matrices of circRNAs and drugs from MHGT are decoded through inner product to obtain the predicted circRNA-drug sensitivity associations. Extensive cross-validation experiments demonstrate that MHGTCDA outperforms nine other state-of-the-art methods. Case studies further illustrate the excellent predictive ability of the proposed method. These results highlight the potential of MHGTCDA as a valuable method for predicting circRNA-drug sensitivity associations, offering significant benefits to drug development.

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Data availability

The data sets and source codes used in this study are freely available at https://github.com/yinboliu-git/MHGTCDA.

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Funding

This work was supported by the Young Wanjiang Scholar Program of Anhui Province and the Research Program of Education Department of Anhui Province (2023AH050998).

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yinbo Liu, Xinxin Ren and Jun Li. The first draft of the manuscript was written by Yinbo Liu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiaolei Zhu.

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Liu, Y., Ren, X., Li, J. et al. Prediction of circRNA-drug sensitivity using random auto-encoders and multi-layer heterogeneous graph transformers. Appl Intell 55, 238 (2025). https://doi.org/10.1007/s10489-024-05859-3

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