School of Mathematical Sciences, Queen Mary University of London, London, UK.
The Alan Turing Institute, London, UK.
BMC Bioinformatics. 2024 Feb 14;25(1):70. doi: 10.1186/s12859-024-05683-z.
Biological networks have proven invaluable ability for representing biological knowledge. Multilayer networks, which gather different types of nodes and edges in multiplex, heterogeneous and bipartite networks, provide a natural way to integrate diverse and multi-scale data sources into a common framework. Recently, we developed MultiXrank, a Random Walk with Restart algorithm able to explore such multilayer networks. MultiXrank outputs scores reflecting the proximity between an initial set of seed node(s) and all the other nodes in the multilayer network. We illustrate here the versatility of bioinformatics tasks that can be performed using MultiXrank.
We first show that MultiXrank can be used to prioritise genes and drugs of interest by exploring multilayer networks containing interactions between genes, drugs, and diseases. In a second study, we illustrate how MultiXrank scores can also be used in a supervised strategy to train a binary classifier to predict gene-disease associations. The classifier performance are validated using outdated and novel gene-disease association for training and evaluation, respectively. Finally, we show that MultiXrank scores can be used to compute diffusion profiles and use them as disease signatures. We computed the diffusion profiles of more than 100 immune diseases using a multilayer network that includes cell-type specific genomic information. The clustering of the immune disease diffusion profiles reveals shared shared phenotypic characteristics.
Overall, we illustrate here diverse applications of MultiXrank to showcase its versatility. We expect that this can lead to further and broader bioinformatics applications.
生物网络在表示生物知识方面具有非常宝贵的能力。多层网络将不同类型的节点和边收集在多路、异质和二部网络中,为将各种多尺度数据源集成到一个通用框架中提供了一种自然的方法。最近,我们开发了 MultiXrank,这是一种能够探索这种多层网络的随机游走重新启动算法。MultiXrank 输出的分数反映了初始种子节点集与多层网络中所有其他节点之间的接近程度。在这里,我们展示了使用 MultiXrank 可以执行的各种生物信息学任务的多功能性。
我们首先展示了如何使用 MultiXrank 通过探索包含基因、药物和疾病之间相互作用的多层网络来优先考虑感兴趣的基因和药物。在第二项研究中,我们说明了如何在监督策略中使用 MultiXrank 分数来训练二进制分类器以预测基因-疾病关联。使用过时和新的基因-疾病关联分别进行训练和评估来验证分类器性能。最后,我们表明 MultiXrank 分数可用于计算扩散谱并将其用作疾病特征。我们使用包含细胞类型特异性基因组信息的多层网络计算了 100 多种免疫疾病的扩散谱。免疫疾病扩散谱的聚类揭示了共享的表型特征。
总的来说,我们在这里展示了 MultiXrank 的多种应用,以展示其多功能性。我们希望这将导致进一步和更广泛的生物信息学应用。