Large language models encode world models implicitly in neural weights, which exposes four structural risks in high-precision domains such as medicine and finance: hallucination, frozen knowledge, poor explainability, and poor modifiability. This paper proposes data-first ontology: LLMs are treated as reasoning and language engines, while deterministic knowledge is moved into an explicit multimodal database, DaoQL. We formalize an explicit world model and show that, under rule independence, deterministic evaluation, and fixed conflict resolution, explicit models provide a sufficient condition for composable counterfactual decomposability; implicit models lack atomic read/delta semantics and therefore provide no comparable architectural guarantee. The implemented system focuses on DaoQL's verified storage layer and explicit Eval path, integrating graph, column, vector, and full-text engines within one process. KVCache graph nodes, expert hot updates, and the DaoQL-Agent runtime remain future work. On an embedded same-machine setup, DaoQL reports graph BFS at 1.20 ms, HNSW at 83.1 us, and a Fluent hybrid query at 105.8 us; these results indicate engineering potential but must be interpreted with deployment-shape differences from client-server systems. Exploratory measurements on LDBC SNB SF1 and ANN-Benchmarks further show 34/34 query coverage with interactive-class queries mostly in the sub-millisecond to millisecond range, but only 1.8 QPS overall due to long-tail BI/IC queries; ANN-Benchmarks reaches Recall@10>= 99% at thousand-level QPS after a bridge-edge protection fix. In a five-domain counterfactual experiment (n = 1250), DaoQL+GPT-4o achieves 94% composable counterfactual decomposability, 49 percentage points above GPT-4o alone. The paper explicitly separates provable structure, preliminary empirical evidence, and architectural roadmap claims.
Single-cell transcriptomics has enabled systematic profiling of cellular states across ordered biological contexts, including developmental stages, treatment phases, disease progression, and anatomical compartments. A central challenge is to reconstruct trajectories that respect the directionality imposed by biology or experimental design. Existing trajectory inference methods reconstruct cell-state progressions from latent-space geometry but do not enforce external biological ordering during graph construction, yielding biologically inadmissible transitions. An emerging paradigm of optimal-transport (OT) approaches partially addresses this limitation by incorporating experimental ordering into probabilistic state-to-state correspondences, yet their pairwise formulation cannot resolve whether a given state is an intermediate state or a terminal state along a multi-step progression. In multi-timepoint settings, OT typically estimates couplings only betweenadjacent timepoints and then chains these locally solved couplings to approximate long-range trajectories without a global optimization across all conditions simultaneously. Here we present SPARC, a graph-based optimization framework that quantifies similarity in a shared high-dimensional latent space and reconstruct directional trajectories under biological constraints. Global shortest-path optimization over this graph yields progression routes, from which SPARC derives path-based pseudotime identifies bottlenecks clusters, and detects gene temporal behavior. SPARC was evaluated across three complementary settings representing distinct trajectory-inference challenges. Its application to paired primary and lung metastatic osteosarcoma samples allows us to be the first to propose a “cross-organ bone-like microenvironment” hypothesis, in which osteoclastogenic signaling establishes a bone-like remodeling niche within the pulmonary metastatic lesion that promotes osteoclast differentiation and activity. The findings are independently recoverable in human osteosarcoma Visium HD spatial transcriptomics.
Shifeng Wu, W. C. Walker, Carolyn A. Martin et al.· bioRxiv· 0 citations
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