Graph Neural Networks for Double-Strand DNA Breaks Prediction
Authors: XU Wang, Huan Zhao, Weiwei TU, Hao Li, Yu Sun, Xiaochen Bo
AI-generated Key Points
- Double-strand DNA breaks (DSBs) can cause abnormal chromosomal rearrangements
- Detecting DSBs using high-throughput experiments is costly and technically challenging
- GraphDSB is a graph neural network-based method that predicts DSBs using DNA sequence features and chromosome structure information
- The model incorporates Jumping Knowledge architecture and several effective structural encoding methods to improve its expression ability
- GNNExplainer is used to analyze the contribution of node features and topology to DSB prediction, revealing that 5-mer DNA sequence features and two chromatin interaction modes have a high contribution
- Compared to other low-cost, high-efficiency DSB prediction methods such as Random Forest-based models, GraphDSB leverages chromosome structure information resulting in improved accuracy
- Studies show that GraphDSB outperforms other GNN variants on NHEK and K562 datasets
- This study proposes an effective method for predicting DSBs using graph neural networks based on DNA sequence features and chromosome structure information which improves accuracy compared to other low-cost methods while reducing technical challenges associated with high-throughput experiments
- Future work could explore how this approach could be applied in clinical settings or extended beyond human cells to other organisms
Abstract: Double-strand DNA breaks (DSBs) are a form of DNA damage that can cause abnormal chromosomal rearrangements. Recent technologies based on high-throughput experiments have obvious high costs and technical challenges.Therefore, we design a graph neural network based method to predict DSBs (GraphDSB), using DNA sequence features and chromosome structure information. In order to improve the expression ability of the model, we introduce Jumping Knowledge architecture and several effective structural encoding methods. The contribution of structural information to the prediction of DSBs is verified by the experiments on datasets from normal human epidermal keratinocytes (NHEK) and chronic myeloid leukemia cell line (K562), and the ablation studies further demonstrate the effectiveness of the designed components in the proposed GraphDSB framework. Finally, we use GNNExplainer to analyze the contribution of node features and topology to DSBs prediction, and proved the high contribution of 5-mer DNA sequence features and two chromatin interaction modes.
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