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Chrombus-XMBD: A Graph Generative Model Predicting 3D-Genome, ab initio from Chromatin Features

Zeng, Y.; You, Z.; Guo, J.; Zhao, J.; Zhou, Y.; Huang, J.; Lyu, X.; Chen, L.; Li, Q.

2023-08-05 bioinformatics
10.1101/2023.08.02.551072 bioRxiv
Show abstract

AbstractsThe landscape of 3D-genome is crucial for transcription regulation. But capturing the dynamics of chromatin conformation is costly and technically challenging. Here we described "Chrombus-XMBD", a graph generative model capable of predicting chromatin interactions ab inito based on available chromatin features. Chrombus employes dynamic edge convolution with QKV attention setup, which maps the relevant chromatin features to a learnable embedding space thereby generate genomewide 3D-contactmap. We validated Chrombus predictions with published databases of topological associated domains (TAD), eQTLs and gene-enhancer interactions. Chrombus outperforms existing algorithms in efficiently predicting long-range chromatin interactions. Chrombus also exhibits strong generalizability across different cell lineage and species. Additionally, the parameter sets of Chrombus inform the biological processes underlying 3D-genome. Our model provides a new perspective towards interpretable AI-modeling of the dynamics of chromatin interactions and better understanding of cis-regulation of gene expression.

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