SemNet Explorer: An Evidence-Grounded Knowledge Graph-LLM Framework for Multi-Scale Mechanistic Reporting Across Biomedical Domains.

BACKGROUND: Mechanistic reporting from large-scale biomedical knowledge graphs remains challenging, particularly when integrating structured graph evidence with large language model (LLM)-based explanation in a reproducible and auditable manner. Existing approaches either rely on manual synthesis of graph-derived results or generate unconstrained narratives that lack traceability to underlying evidence. METHODS: We present SemNet Explorer, an evidence-grounded knowledge graph-LLM unified framework for automated mechanistic reporting across biomedical domains using SemNet 2.0, a PubMed-scale heterogeneous knowledge graph. Given a set of target concepts and a selected semantic layer, the framework organizes graph-derived evidence into structured regions and generates two complementary report types: global reports for process-level mechanisms and anchor-centric reports for localized mediator-based explanations. A central methodological contribution is an ablation-derived adaptive grounding policy: we systematically compare alternative evidence-integration strategies across report types, semantic layers, and region structures, and use the resulting preferences to guide prompt selection in the deployed system. RESULTS: SemNet Explorer produces stable region decompositions and interpretable report scaffolds across molecular (AAPP), disease-level (DSYN), and pharmacologic (PHSU) representations. For global reports, explicit evidence grounding improves expression quality more consistently than content accuracy, with benefits dependent on evidence density and semantic abstraction. In contrast, anchor-centric reports show consistent improvements in both content and expression under stronger, mediator-constrained prompting. These findings are supported by both pairwise ablation comparisons and absolute score analyses. CONCLUSIONS: SemNet Explorer establishes a generalizable unified framework and interactive platform for transforming knowledge graph evidence into reproducible mechanistic narratives across biomedical domains, including multimorbidity analysis, comparative pathophysiology, drug repurposing, and adverse event discovery. The results demonstrate that effective knowledge graph-LLM integration requires adaptive, context-dependent evidence grounding rather than fixed prompting strategies.