Sparse Contextual Coupling Reshapes Diffusion Geometry in Multilayer Hypergraphs
稀疏上下文耦合重塑多层超图中的扩散几何
Hao Ding, Sanjukta Krishnagopal
AI总结 该研究提出了一种基于扩散的框架,用于分析稀疏条件特定层如何重塑多层超图中的扩散几何,通过将密集的MSigDB功能基因集层与稀疏的疾病特定DGIdb药物-基因超图耦合,发现稀疏层对扩散距离和社区结构有显著影响。
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许多复杂系统结合了密集的背景结构与稀疏的上下文信息。我们介绍了一种基于扩散的框架,用于分析稀疏条件特定层如何重塑多层超图中的扩散几何。每个层被表示为加权超图,层通过共享实体耦合,耦合系统上的随机游走诱导节点间的多尺度扩散距离。我们通过将密集的MSigDB功能基因集层与稀疏的疾病特定DGIdb药物-基因超图耦合,利用疾病相关的药物从DDDB和HumanNet-GSP定义外部基因权重,发现疾病特定层在耦合系统中包含不到2%的基因,但显著改变了扩散距离和社区结构。中心性分析表明,这种不成比例的影响是由于DGIdb关联的基因在MSigDB衍生的功能网络中占据重要位置。所得到的扩散衍生社区在子采样下保持稳定,并显示后验功能富集的一致性,包括神经精神疾病中的信号和神经递质类别,以及癌症相关疾病中的免疫、翻译和代谢类别。社区层面的比较进一步揭示了疾病相似性,这些相似性无法仅通过直接DGIdb基因重叠来解释,包括乳腺癌与精神分裂症的关系,这与最近的生物医学证据一致。这些结果表明,稀疏上下文层可以诱导在更高阶网络几何中的可解释非局部变化。
Many complex systems combine dense background structure with sparse contextual information. We introduce a diffusion-based framework for analyzing how sparse condition-specific layers reshape diffusion geometry in multilayer hypergraphs. Each layer is represented as a weighted hypergraph, layers are coupled through shared entities, and random walks on the coupled system induce multiscale diffusion distances between nodes. We apply the framework to disease-conditioned gene networks by coupling a dense MSigDB functional gene-set layer to sparse disease-specific DGIdb drug-gene hypergraphs, with disease-associated drugs selected from DDDB and HumanNet-GSP used to define external gene weights. Across Bipolar Disorder, Schizophrenia, Leukemia, and Breast Cancer, the disease-specific layer contains less than 2 percent of genes in the coupled system, yet substantially changes diffusion distances and community structure. Centrality analysis suggests that this disproportionate effect arises because DGIdb-associated genes occupy influential positions in the MSigDB-derived functional network. The resulting diffusion-derived communities are stable under subsampling and show coherent post hoc functional enrichment, including signaling and neurotransmission categories in neuropsychiatric diseases and immune, translational, and metabolic categories in cancer-associated diseases. Community-level comparisons further reveal disease similarities not reducible to direct DGIdb gene overlap, including a Breast Cancer-Schizophrenia relationship consistent with recent biomedical evidence. These results show that sparse contextual layers can induce interpretable nonlocal changes in higher-order network geometry.