Can Broad Biomedical Knowledge be Contextualized into Scenario-Grounded Propositions?

Translational medicine turns underspecified development goals into evidence synthesis that must combine literature, trials, patents, and quantitative multi-omics analysis while preserving identifiers, uncertainty, and retrievable provenance. General-purpose foundation models and off-the-shelf tool-augmented or multi-agent systems are not built for this: they tend to produce single-shot answers or run open-endedly, and fall short on the auditable, scenario-specific workflows that heterogeneous biomedical sources demand. This paper introduces Ingenix BioResearcher, a scenario-guided multi-agent system that maps queries to versioned research playbooks, delegates to specialized subagents over 30+ tools and machine-learning endpoints, mixes structured database access with sandboxed code for genome-scale analyses, and applies claim-level multi-model reconciliation before editorial assembly. We evaluate BioResearcher across unit-level capabilities, open-ended biomedical reasoning, and end-to-end clinical discovery. It leads evaluated baselines on 109 single-step tests (83.49% pass rate; 0.892 average score), achieves strong biomedical benchmark performance (89.33% on BixBench-Verified-50 and the top 0.758 mean score on BaisBench Scientific Discovery), and leads on a 30-query clinical end-to-end benchmark with the highest positive hit rate (74.7% $\pm$ 3.3%) and negative clear rate (96.8% $\pm$ 0.2%). These results show broad, competitive performance across unit-level, open-ended, and end-to-end clinical evaluations.

Large language models (LLMs) can generate biomedical hypotheses, but it remains unclear whether they truly reason from scientific evidence or simply produce convincing-sounding ideas. To study this, we combine three major biological databases: the Kyoto Encyclopedia of Genes and Genomes (KEGG), Rhea, and UniProt, into a unified biochemical knowledge graph and construct a benchmark of 550 paths connecting enzyme sources to rare disease endpoints, yielding 13,200 hypotheses from six LLMs under four conditions varying the biological information each model receives: source enzyme only, full biological path, or source and disease endpoint only. Hypotheses are scored using an expert-derived five-criterion rubric on a 1-5 scale per criterion. We find that models given both the source and disease endpoint often produce the highest-scoring hypotheses, showing that LLMs can generate compelling ideas from minimal information. However, these hypotheses are less grounded in the evidence. In contrast, models given the full biological path generate hypotheses more consistent with known mechanistic relationships. We call this evidence-disciplined reasoning. To confirm this effect, we shuffled intermediate path steps while keeping endpoints fixed. Evidence grounding dropped significantly (delta = -0.793, p < 0.001), confirming models genuinely used path structure during reasoning. Our findings show that knowledge graphs support hypothesis generation in two ways: they identify biological endpoint pairs absent from the literature, and their mechanistic paths guide how LLMs reason between them.

Accumulated scientific knowledge advances inquiry when prior findings help researchers choose new questions, design investigations, and interpret results. Realizing this value at scale requires access to the reasoning that connects research problems, scientific procedures, conclusions, and evidence. We introduce the Large Knowledge Model (LKM), a scientific knowledge infrastructure that transforms the literature into a shared, computationally accessible reasoning resource. LKM represents papers as source-grounded reasoning graphs, couples structural traversal with semantic retrieval over the same objects, and aligns related questions, claims, and reasoning chains across papers. This representation forms a Scientific Reasoning Landscape with three connected views: a Question Landscape that organizes research problems and open directions, a Workflow Landscape that exposes reusable scientific procedures, and an Evidence Landscape that connects conclusions to their support, disagreement, and conditions. The unified substrate supports reasoning-aware scientific search, evidence-grounded question answering, comparative evidence analysis, and research planning. Researchers and agents can retrieve relevant work through its scientific intent, synthesize answers with inspectable supporting arguments, and develop research plans informed by established workflows and unresolved evidence. We describe a corpus-scale system and evaluate scientific retrieval and knowledge-intensive question answering. With the answering model fixed, LKM retrieval improves accuracy by 9.30%, 4.20%, and 14.69% on ChemBench, PubMedQA, and SciBench, respectively. By connecting knowledge access to scientific reasoning and action, LKM provides a common foundation for discovering relevant research, reusing scientific knowledge, and coordinating cumulative inquiry across researchers, agents, and research cycles.