Evidence-Grounded Frontier Mapping and Agentic Hypothesis Generation in Nanomedicine
Authors: Christiaan G. A. Viviers, Koen de Bruin, Mirre M. Trines, Ayla M. Hokke, Roy van der Meel, Avi Schroeder, Twan Lammers, Willem J. M. Mulder, +1 more
Abstract
Nanomedicine research spans delivery chemistry, immunology, imaging, biomaterials, and disease-specific translational science, yet its conceptual design space remains fragmented across a large and heterogeneous literature. To date, artificial intelligence in nanomedicine has focused primarily on property prediction and formulation optimization, with much less attention to evidence-grounded discovery support at the level of research direction selection. We introduce pArticleMap, a literature-mapping and research-hypothesis-generation system that combines article embeddings, similarity-graph analysis, sparse frontier extraction, structured evidence-pack retrieval, and an audited large-language-model (LLM) workflow for grounded ideation. Rather than forecasting future concept co-occurrence, pArticleMap targets low-density article-level bridge regions and cluster interfaces, then generates and scores citation-grounded hypotheses with large language models in an agentic setup. We evaluate the system with a retrospective realization benchmark (generate later literature under a historical cutoff) and a blinded human reader assessment layer across cue-conditioned nanomedicine tasks. Across 4 selected retrospective bundles, pArticleMap generated ideas and selected task-retained hypotheses (winner ideas) under the benchmark protocol. For task-level retained hypotheses, a pooled gold recovery rate of 10.8% was obtained, with a recall@10 of 15.9% and a future-neighborhood rate of 61.0%, indicating that the system often reached the correct forward-looking neighborhood (paper ideas) even without exact paper-level recovery. Human-agent agreement is modest overall, indicating that internal scoring is useful as a support signal but does not replace expert judgment. These results position pArticleMap as a conservative, evidence-grounded research assistant for nanomedicine.
We describe Research Assistant, an internal LLM-based system developed at AstraZeneca to help scientists and clinicians explore biomedical questions across a broad range of data sources. The system provides a chat-style interface that brings together evidence from scientific literature, knowledge graphs, chemistry, clinical trials, safety resources, expression data, and internal experimental systems. It supports both a fast mode for direct question answering and a multi-step mode for more complex research tasks. Responses are grounded in retrieved evidence and linked back to the original sources, allowing users to review and further explore the underlying data. In this technical note, we outline the system architecture, the main design choices behind the product, and lessons learned from deploying it at scale to support day-to-day R&D workflows across AstraZeneca.
Piotr Grabowski, Mohamed Alameen, Jorge Bretones +16
Identifying promising research directions in fast-moving subareas is one of the most cognitively expensive tasks in modern AI research. Existing LLM-driven scientific discovery systems are typically limited to one-shot prompting on static literature snapshots and are validated only against contemporary judges such as human reviewers, agent peer review, wet-lab assays, or self-evaluation, leaving open whether they can anticipate future trends. We present Continuous Knowledge Metabolism (CKM), an AI workflow for hypothesis generation with three key capabilities: (i) continuous literature metabolism via sliding windows that maintain an evolving knowledge state; (ii) predictive evaluation, which grades hypotheses against papers published after the generation window; and (iii) practitioner-grade failure detection that diagnoses workflow failure modes from its outputs. On a 50-topic machine learning benchmark, CKM-Lite produces at least one validated hypothesis on 72% of topics (36 out of 50), more than doubling a one-shot baseline (30%) at approximately 3 dollars per topic and achieving 91% lower token cost. Validated hypotheses precede their matched papers by an average of 404 days (55 hits across 36 topics; median 399 days, range 66-757 days). Broadly, predictive validation against future literature provides a falsifiable, low-cost alternative to contemporary-judge evaluation protocols and can be applied wherever a corpus has dated publication records.
Scientific ideation unfolds over multiple stages, including literature search, paper reading, tool use, claim checking, cross-paper synthesis, brainstorming, rejection of weak directions, and iterative writing. Yet most existing resources capture isolated components or final artifacts rather than the process connecting them. We introduce IdeaTrail, a dataset of 1,170 multi-turn trajectories for scientific ideation and proposal generation. Each trajectory follows a research process from evidence gathering to either idea selection or proposal construction, jointly recording tool use, acquired evidence, intermediate artifacts, and reasoning. IdeaTrail is synthesized from human-selected research papers and proposal artifacts through a Generator--Advisor loop. The Generator produces the visible sequence of actions, observations, and artifact edits, while the Advisor uses the full generation context to check grounding, causal order, naturalness, and leakage from hidden targets. This reverse-to-forward design keeps trajectories aligned with real scientific artifacts while retaining the uncertainty, evidence use, and staged convergence characteristic of research practice. IdeaTrail provides both reusable process supervision and a general recipe for constructing scientific-research-agent data.