Unified Knowledge-Guided Molecular Graph Encoder with multimodal fusion and multi-task learning.

The remarkable success of Graph Neural Networks underscores their formidable capacity to assimilate multimodal inputs, markedly enhancing performance across a broad spectrum of domains. In the context of molecular modeling, considerable efforts have been made to enrich molecular representations by integrating data from diverse aspects. Nevertheless, current methodologies frequently compartmentalize geometric and semantic components, resulting in a fragmented approach that impairs the holistic integration of molecular attributes. This constrained scope limits the generalizability and efficacy of such models in downstream applications. A pivotal challenge lies in harmonizing heterogeneous data sources, particularly in addressing the inherent inconsistencies and sparsity within multimodal molecular datasets. To overcome these limitations, we present the Unified Knowledge-Guided Molecular Graph Encoder (UKGE), a groundbreaking framework that leverages heterogeneous graphs to unify the representation of diverse molecular modalities. Unlike prior methods, UKGE reconciles geometric and semantic features through the use of elemental knowledge graphs (KGs) and meta-path definitions by constructing Unified Molecular Graphs, enabling comprehensive and unified molecular representations. It employs an innovative Meta-Path Aware Message Passing mechanism within its molecular encoder, enhancing the integration of multimodal data. Additionally, a multi-task learning strategy balances data from different modalities, further enriching UKGE's capability to embed complex biological insights.Empirical evaluations highlight UKGE's excellence across tasks: DDI prediction achieves 96.91% ACC and 99.14% AUC in warm-start settings, with 83.15% ACC in cold-start scenarios. For CPI prediction, it reaches 0.644 CI on Davis and 0.659 on KIBA. In LBDD, it achieves 99.3% validity, 98.4% uniqueness, and 98.9% novelty, establishing UKGE as a state-of-the-art molecular modeling framework.