MOTIVATION: Drug combinations can not only enhance drug efficacy but also effectively reduce toxic side effects and mitigate drug resistance. With the advancement of drug combination screening technologies, large amounts of data have been generated. The availability of large data enables researchers to develop deep learning methods for predicting drug targets for synergistic combination. However, these methods still lack sufficient accuracy for practical use, and most overlook the biological significance of their models. RESULTS: We propose the HIG-Syn (hypergraph and interaction-aware multigranularity network for drug synergy prediction) model, which integrates a coarse-granularity module and a fine-granularity module to predict drug combination synergy. The former utilizes a hypergraph to capture global features, while the latter employs interaction-aware attention to simulate biological processes by modeling substructure-substructure and substructure-cell line interactions. HIG-Syn outperforms state-of-the-art machine learning models on our validation datasets extracted from the DrugComb and GDSC2 databases. Furthermore, the fact that five of the 12 novel synergistic drug combinations predicted by HIG-Syn are strongly supported by experimental evidence in the literature underscores its practical potential. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/gracygyx/HIGSyn.

BACKGROUND: Uncovering the evolutionary principles of gene coexpression network is important for our understanding of the network topological property of new genes. However, most existing evolutionary models only considered the evolution of duplication genes and only based on the degree of genes, ignoring the other key topological properties. The evolutionary mechanism by which how are new genes integrated into the ancestral networks are not yet to be comprehensively characterized. Herein, based on the human ribonucleic acid-sequencing (RNA-seq) data, we develop a new evolutionary model of gene coexpression network which considers the evolutionary process of both duplication genes and de novo genes. RESULTS: Based on the human RNA-seq data, we construct a gene coexpression network consisting of 8061 genes and 638624 links. We find that there are 1394 duplication genes and 126 de novo genes in the network. Then based on human gene age data, we reproduce the evolutionary process of this gene coexpression network and develop a new evolutionary model. We find that the generation rates of duplication genes and de novo genes are approximately 3.58/Myr (Myr=Million year) and 0.31/Myr, respectively. Based on the average degree and coreness of parent genes, we find that the gene duplication is a random process. Eventually duplication genes only inherit 12.89% connections from their parent genes and the retained connections have a smaller edge betweenness. Moreover, we find that both duplication genes and de novo genes prefer to develop new interactions with genes which have a large degree and a large coreness. Our proposed model can generate an evolutionary network when the number of newly added genes or the length of evolutionary time is known. CONCLUSIONS: Gene duplication and de novo genes are two dominant evolutionary forces in shaping the coexpression network. Both duplication genes and de novo genes develop new interactions through a "rich-gets-richer" mechanism in terms of degree and coreness. This mechanism leads to the scale-free property and hierarchical architecture of biomolecular network. The proposed model is able to construct a gene coexpression network with comprehensive biological characteristics.