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MDSGCN: Predicting Multiple Types of Mutation-Drug Association Through Signed Graph Convolution Network
Abstract:
Cancer constitutes a significant global public health challenge, resulting in millions of fatalities annually. Gene mutations are pivotal in initiating and advancing cancer, disrupting regular cellular growth and differentiation mechanisms, thereby fostering tumor development. Consequently, comprehending the intricacies of gene mutations and their interplay with pharmaceuticals is imperative for cancer prevention, diagnosis, and treatment. Despite drug therapy being a cornerstone in cancer treatment, prognosticating and assessing multiple types of mutation-drug association remains a laborious and costly work. To address this problem, we develop a deep learning model grounded in signed graph convolution network (MDSGCN) to predict multiple types of mutation-drug association. We establish mutation-drug association as a signed bipartite network, comprising mutation nodes, drug nodes and two edge types including sensitive or resistant of mutations in drugs. MDSGCN extracts the subgraphs from the mutation-drug pairs in signed bipartite network, utilizing a label algorithm to learn subgraph structural features. Furthermore, MDSGCN integrates biological features (i.e., mutation-mutation similarity and drug-drug similarity) as the auxiliary information with the subgraph structural features to construct the prediction model. Experimental results demonstrate that our model consistently outperforms the state-of-the-art methods. The case study shows that MDSGCN can discover novel mutation-drug association and the association type.
Insights
This study introduces a deep learning model, MDSGCN, to predict gene mutation-drug associations for cancer treatment. The model accurately identifies sensitive or resistant mutation-drug relationships, aiding in personalized cancer therapy.
Area of Science:
- Oncology
- Bioinformatics
- Computational Biology
Background:
- Cancer is a major global health issue driven by gene mutations.
- Understanding mutation-drug interactions is crucial for cancer treatment but challenging.
- Current methods for assessing mutation-drug associations are laborious and expensive.
Purpose of the Study:
- To develop a novel deep learning model for predicting multiple types of mutation-drug associations.
- To improve the efficiency and accuracy of identifying clinically relevant mutation-drug relationships.
- To aid in personalized cancer treatment strategies by predicting drug sensitivity or resistance.
Main Methods:
- A signed graph convolution network (MDSGCN) model was developed.
- Mutation-drug associations were represented as a signed bipartite network.
- The model learned subgraph structural features and integrated biological similarities (mutation-mutation and drug-drug).
Main Results:
- The MDSGCN model demonstrated superior performance compared to existing state-of-the-art methods.
- Experimental results confirmed the model's effectiveness in predicting mutation-drug associations.
- A case study highlighted the model's ability to discover novel mutation-drug relationships and their types.
Conclusions:
- MDSGCN offers a powerful computational approach for predicting mutation-drug associations in cancer.
- The model can accelerate the discovery of targeted therapies and improve cancer treatment outcomes.
- This work advances the integration of deep learning and network analysis in precision oncology.
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