POINT: a web-based platform for pharmacological investigation enhanced by multi-omics networks and knowledge graphs

Network pharmacology (NP) explores pharmacological mechanisms through biological networks. Multi-omics data enable multi-layer network construction under diverse conditions, requiring integration into NP analyses. We developed POINT, a novel NP platform enhanced by multi-omics biological networks, advanced algorithms, and knowledge graphs (KGs) featuring network-based and KG-based analytical functions. In the network-based analysis, users can perform NP studies flexibly using 1,158 multi-omics biological networks encompassing proteins, transcription factors, and non-coding RNAs across diverse cell line-, tissue- and disease-specific conditions. Network-based analysis-including random walk with restart (RWR), GSEA, and diffusion profile (DP) similarity algorithms-supports tasks such as target prediction, functional enrichment, and drug screening. We merged networks from experimental sources to generate a pre-integrated multi-layer human network for evaluation. RWR demonstrated superior performance with a 33.1% average ranking improvement over the second-best algorithm, PageRank, in identifying known targets across 2,002 drugs. Additionally, multi-layer networks significantly improve the ability to identify FDA-approved drug-disease pairs compared to the single-layer network. For KG-based analysis, we compiled three high-quality KGs to construct POINT KG, which cross-references over 90% of network-based predictions. We illustrated the platform's capabilities through two case studies. POINT bridges the gap between multi-omics networks and drug discovery; it is freely accessible at http://point.gene.ac/.