Scientific Hypothesis Generation

Ideation plays a pivotal role in scientific discovery. Recent LLM, especially AI Scientist systems, show promising potential for automated ideation. However, existing approaches predominantly rely on pre-defined agentic workflows. This constraint severely limits the flexibility required to navigate the vast search space of scientific literature and the complex action space of research reasoning. Recently, training Agentic LLMs has emerged as a promising direction, offering flexible reasoning frameworks and the capability for autonomous tool utilization. However, there remains a non-trivial challenge: applying previous agentic data synthesis methods to scientific ideation suffers from prohibitively high data synthesis cost. To bridge this gap, we propose Agentic-Ideation, a novel framework comprising an automated trajectory synthesis pipeline and a specialized agentic LLM trained for scientific ideation. Specifically, we first define a comprehensive tool space incorporating three external tools and three cognitive tools. Then we introduce an Oracle-Guided Data Synthesis strategy. By leveraging a reference idea as oracle guidance, this approach steers the multi-agent system to efficiently reconstruct the logical reasoning and tool invocation paths, transforming aimless trial-and-error into directed trajectory generation. Finally, we train the agent on these synthesized trajectories, employing a masking strategy on tool execution results. This ensures the model focuses on decision-making logic without interference from external feedback. Experimental results demonstrate that our method outperforms the SOTA workflow-based baseline by \textbf{11.91%} in overall quality. Furthermore, our approach improves the sample efficiency of high-quality data synthesis by \textbf{over 10$\times$}.

Open-ended scientific discovery with large language models (LLMs) increasingly operates as a long-horizon loop of hypothesis search and verification, where a reward signal guides which hypotheses to test next. A notable recent example is AutoDiscovery, which uses "Bayesian surprise" - the belief shift an LLM undergoes after observing evidence for a hypothesis - as both a discovery metric and a reward for search. We first observe that AutoDiscovery treats surprisal as a static quantity, while surprisal in human reasoning is non-stationary - it is defined relative to beliefs that evolve with experience, a prerequisite for continual scientific discovery. We address this mismatch with evidence-informed LLM beliefs: priors updated with evidence from previous hypotheses to compute non-stationary surprisal for new hypotheses. We compare in-context belief-updating mechanisms and find that embedding-based retrieval-augmented generation over prior discoveries best anticipates eventual posteriors, identifying 37.5% of static surprisals as spurious. We then modify search to avoid these spurious rewards and prioritize hypotheses that remain surprising under non-stationary beliefs. Concretely, we introduce two complementary changes to the original search procedure: belief-update filtering and diversity maximization. Across five discovery domains, our method increases accumulated non-stationary surprisal by 30.62% on average compared to the original search procedure, demonstrating that continual scientific discovery with LLMs requires not only better belief measurement but also search procedures that avoid redundancy and encourage diversity.

The automation of scientific discovery has reached an inflection point. While AI systems now operate instruments, optimize parameters and generate hypotheses, most remain procedural: they execute workflows fixed by human designers. True autonomous science demands epistemic autonomy--the capacity to construct, challenge and revise physical explanations in response to evidence. Here we introduce AHOIS, a multi-agent AI scientist that embeds Socratic midwifery into closed-loop experimentation. A physics-critic agent interrogates hypotheses through causal questioning, constraint checking, counterexample generation and falsification-criteria formulation. We evaluate AHOIS on a real multimode-fibre optical platform, a high-dimensional system with complex wave transformations, indirect detection, environmental drift and multi-modal acquisition. Without prior encoding schemes, classifiers or speckle models, the system autonomously proposed and validated a random-interference encoding hypothesis, discovered task-adaptive sparse-measurement strategies, diagnosed distinct failure modes (encoding instability, fluorescence contamination and detector noise) and translated a published imaging protocol into an executable workflow on a non-original configuration. The discovered encoding yielded 16x16 measurements with effective rank 56.9 and classification accuracies of 76.97% on MNIST and 83.17% on Fashion-MNIST. Ablations show that Socratic interrogation improves physical consistency, hypothesis completeness, uncertainty calibration and experimental-plan validity. These results establish a route from workflow automation towards evidence-grounded, self-correcting autonomous discovery in complex physical environments.

Agentic artificial intelligence (AI) systems are beginning to assist, accelerate, and partially automate scientific discovery, performing tasks that span literature synthesis, code generation, data analysis, hypothesis proposal, and model criticism. We argue that this transition is qualitative rather than incremental, and that suitably designed multi-agent systems may evolve from passive computational tools into ``AI scientists'' that can expand the hypothesis-generating and verification capacity of science. Such systems must be developed and deployed within a scientific ecosystem fit for purpose: institutions must be redesigned for verification, accountability, interpretability, and dual-use safety. We sketch how multi-agent architectures, illustrated by the prototype framework \textit{Denario}, accelerate the discovery cycle and traverse model spaces beyond human reach; examine what this implies for authorship, peer review, and the enduring role of human scientists; and close with recommendations for governing AI as an epistemic actor rather than a mere instrument.

Scientific discovery saturates when new hypotheses cease to provide independent information, even if the nominal hypothesis space remains large. We study hybrid discovery systems that combine structured local search with LLM-generated non-local proposals and pose the Search Compression Hypothesis: non-local exploration helps only when three geometric conditions co-occur: spectral compression, orthogonal escape from the explored span, and residual signal alignment with the target. We formalize these conditions, derive necessary conditions for hybrid advantage, and test the mechanism in controlled synthetic environments, large-scale A-share factor discovery, and symbolic-regression benchmarks; a public tabular operational sanity check tests the associated budget-allocation implication. Signal-planting and directed-versus-random experiments show that novelty alone is insufficient: random orthogonal jumps expand coverage but do not improve yield without predictive alignment. Across compression sweeps, real factor archives, and LLM-SRBench tasks, hybrid gains concentrate in weakly represented but target-bearing directions and vanish as the hypothesis space approaches full rank. The framework turns LLM-guided discovery from generic novelty search into a diagnostic procedure for deciding when directed non-local exploration is warranted.

Large language models (LLMs) are on the rise for accelerating scientific discovery, most recently in advanced tasks such as generating valid scientific hypotheses. Yet in many discovery settings, the goal is not to identify a single best hypothesis since validation can be noisy and expensive, and scientists benefit from a set of high-quality alternative hypotheses that hedge against downstream uncertainty for the best solutions. Nevertheless, commonly used evolutionary search recipes tend to prioritize optimization over exploration in hypothesis generation, and the resulting selection pressure during the search process leads to diversity collapse. Motivated by these limitations, we formulate hypothesis search as a sampling problem, where the objective is to efficiently produce diverse, high-quality hypotheses under a fixed validation budget. Building on this perspective, we propose \ours, an evolutionary framework inspired by the classical parallel tempering algorithm that searches hypotheses at multiple temperature levels and enables principled information exchange across temperatures to improve exploration without disrupting convergence. Across domains including molecular discovery, equation discovery, and algorithm discovery, our approach consistently improves both hypothesis quality and diversity under the same validation budget, and produces candidates that remain robust under more expensive downstream computational validations.

Generating novel, feasible, and high-quality research ideas is an important yet challenging task in scientific discovery. Recent Large Language Model (LLM)-based methods often ground idea generation with retrieved literature, but the retrieved evidence is usually provided as flat text, such as titles, abstracts, or summaries. Such flat contexts may contain redundant or weakly relevant information, while making cross-paper relations among problems, methods, mechanisms, and findings difficult to identify and trace. To address this challenge, we propose Graph2Idea, a knowledge graph-guided framework for retrieval-augmented scientific idea generation.Graph2Idea first retrieves papers according to the input topic, transforms them into structured knowledge triples, and dynamically constructs a target-centered knowledge graph to make literature relations explicit. It then extracts compact graph-derived contexts that retain target-relevant relational evidence while reducing noisy textual input. Based on these contexts, a two-stage generation process first identifies promising research directions and then guides the LLM to synthesize candidate ideas from graph-grounded evidence. Experiments on a scientific idea generation benchmark show that Graph2Idea outperforms representative baselines under the automatic evaluation protocol. Compared with the strongest baseline scores, it improves Novelty from 0.45 to 0.52, Quality from 0.24 to 0.29, and Feasibility from 0.22 to 0.28. These results suggest that graph-structured evidence helps LLMs generate research ideas through more explicit, compact, and traceable recombination of prior scientific knowledge.

Modern artificial intelligence excels at prediction but cannot explain. From large language models to AI-for-science systems, today's machines answer what by recombining patterns already present in the human literature, yet they cannot reason out why a phenomenon must arise from underlying principles even though explanation, not prediction, lies at the heart of scientific discovery. Here we ask whether the structure of scientific explanation can be operationalized to guide how a machine generates hypotheses. We introduce DN-Hypo-Pipeline, a hypothesis-generation framework that adopts a layered, explanation-theoretic scaffold: Hempel's deductive-nomological (DN) model supplies the output form and deductive validity of a hypothesis, Salmon's causal-process account supplies an organizing constraint on where to search for the governing laws, and Armstrong's view of laws as relations between universals supplies the bridge from a phenomenon's constituent processes to the laws that may be associated with it. Rather than searching the space of what has been written, the framework searches the space of what principles govern a phenomenon: given an explanandum, it abstracts the universals instantiated in the phenomenon's formation process, retrieves the laws relating those universals, and deductively reconstructs a new, testable explanation. Evaluated in data-science modeling and judged by both LLMs and human experts, hypotheses generated through this principled reasoning significantly outperform those from direct prompting. Crucially, we translated the two highest-scoring hypotheses into novel algorithms one that reduces the Transformer's theoretical complexity with only minimal performance loss, and another that achieves competitive accuracy with substantially fewer parameters.

Bold projections that artificial intelligence will accelerate scientific discovery have raced ahead of evidence from working scientists, and the field still lacks large-scale, scientist-in-the-loop tests of these claims. Here we mount the largest such evaluation to date and map what AI cannot yet do for science. We invited authors of 121,640 recent preprints across biology, medicine, chemistry, and the social sciences to judge ideas that large language models (LLMs) generated from the context and puzzles of their own papers. 6,749 scientists returned 25,139 sets of ratings on novelty, empirical feasibility, probability of being true, and favorability of adoption. Three patterns emerge. First, non-reasoning LLMs collapse into a narrow "hivemind" of similar ideas; reasoning models roam a wider hypothesis space, yet no model class spontaneously proposes null hypotheses -- a move humans make more freely. Second, scientists reward ideas that resemble their own and prize probability over novelty, though social scientists tolerate risk more readily than life scientists. Senior social scientists are the harshest critics, and their skepticism is well-earned: LLMs falter most in pluralistic fields like the social sciences that demand context-aware interpretation and evolving theories. Third, automated evaluators on which the community currently relies -- LLM-as-a-judge, artificial metrics, and even state-of-the-art (SOTA) models -- agree only weakly with expert judgment, and retrieval augmentation and scientist persona prompting yield only marginal gains. A Qwen3-14B reward model we post-trained on human ratings captures field taste nuances, beats SOTA models by up to 27%, and closes the gap to the inter-rater consistency of independent peer reviewers. For all the hype, today's scientific AI still represents a collaborator whose imagination, outputs and judgment benefit from human grounding.

A core goal of computational social science is to discover interpretable differences in how language varies across outcomes of interest, such as political affiliation or instructional quality. Recent LLM-based hypothesis generation methods describe such differences in natural language, but select for globally discriminative patterns without accounting for covariates that shape the data based on researchers' domain knowledge. When covariates are ignored, selected patterns can reflect confounds rather than differences of substantive interest. We introduce conditional hypothesis generation, a framework that incorporates researcher-specified covariates to steer hypothesis discovery toward differences that hold within relevant subgroups. Two challenges arise: the target subgroup may be underrepresented (stratum imbalance), and the direction of a difference may reverse across subgroups (sign reversal). We propose two econometrics-inspired methods: one introduces feature--covariate interactions to detect sign reversals, and the other applies within-stratum demeaning and inverse-frequency reweighting to equalize underrepresented strata. Synthetic experiments show each method outperforms global baselines in its targeted setting, and expert evaluation on two real-world datasets confirms that covariate-aware generation surfaces more useful hypotheses within relevant subgroups.

Generating novel research ideas is fundamental to scientific progress. While Large Language Models (LLMs) show promise in assisting this process, existing approaches often exhibit semantic convergence, resulting in limited diversity and novelty. To address this, we introduce EvoGens, an evolution-inspired framework that recasts scientific idea generation as an evolutionary search over a population of ideas. EvoGens iteratively applies rank-based mutation with differentiated retrieval planning to incorporate external knowledge, and semantic-aware crossover to fuse complementary concepts for conceptual reorganization. A lightweight evaluation signal guides the selection process, encouraging sustained exploration while mitigating premature convergence. Extensive experiments demonstrate that EvoGens substantially enhances exploration capabilities compared to state-of-the-art baselines. Specifically, it improves the Novelty from 0.1 to 0.4 and the Diversity from 0.24 to 0.55, while maintaining comparable idea quality under the current automatic evaluation protocol. These findings suggest that evolutionary mechanisms can serve as a useful framework for exploration-oriented research ideation, especially for broadening the novelty and diversity of candidate ideas under a shared automatic evaluation setting.

Scientific discovery is an inherently creative and uncertain process, requiring reasoning beyond the recall of known knowledge. While many benchmarks have been proposed to evaluate large language model (LLM) performance on deep research tasks via multi-hop retrieval, their innovative reasoning abilities essential for true scientific discovery remain largely untested. We introduce a benchmark framework for evaluating model performance in scientific discovery and reasoning, building up from a raw problem to the classical null hypothesis test. In our framework, models initially receive only the topic and research question from a recent paper, with technical details progressively revealed. At each stage of information disclosure, the model is tasked with generating hypotheses that address the research question, which is compared with the conclusions from the original paper and evaluated via automated semantic similarity of constituent atomic claims. This progressive evaluation of semantic divergence from ground-truth conclusions enables assessment of a model's innovativeness (under minimal information) to grounded reasoning capabilities (under full experimental details), both critical for using LLMs for scientific discovery purposes. Our framework provides a foundation for systematically evaluating scientific reasoning and discovery capabilities in LLMs, crucial for advancing the development of next-generation AI scientist/co-scientist systems. Specifically, here we evaluate GPT-5, GPT-5.4, Gemini 2.5 pro, and Gemini 3.1 pro preview across 45 papers spanning bioactive materials, mechanical materials, and nanomaterials. We find that GPT-5.4 and Gemini 3.1 pro outperform their previous generation counterparts as expected, and GPT-5.4 in particular maintains 0.7 F1 score alignment with ground truth conclusions even under minimal context.

Large language models (LLMs) show remarkable potential in scientific hypothesis discovery. However, existing approaches face two critical limitations: they treat divergent exploratory search and convergent fine-grained refinement as isolated tasks, and they operate autonomously with little to no human guidance. We present MOOSE-Copilot, the first unified framework to bridge this abstraction gap through a formalized human-AI interaction (HAII) protocol. Our system empowers scientists to steer the generative process via three explicit signals: initial blueprints, inter-stage routing, and intra-stage feedback. Using an oracle-simulated evaluation in which an LLM provides idealized expert signals, we show that injecting these structured signals significantly outperforms purely autonomous baselines, characterizing the gains achievable under high-quality guidance. Furthermore, we build a web-based interface that turns the framework into a no-code workflow: researchers pose a question, watch the hypothesis search unfold as an interactive tree, and steer it by selecting hypotheses, routing between stages, and injecting feedback-no command-line agents required. This makes end-to-end hypothesis discovery directly accessible to interdisciplinary researchers.

AI research agents now support large-scale AI-assisted scientific discovery. We examine whether AI-generated ideas broaden scientific exploration or primarily reinforce existing work. Using five agent frameworks and five large language models, we generate 219,655 ideas for different scientific fields. Across experiments, four consistent patterns emerge. First, AI-generated ideas are more concentrated than human-authored papers within the same research area. Second, they remain much closer to starting literature than later human follow-on work does. Third, AI-generated ideas align less with future human research. Last, AI-generated ideas are located in lower-impact regions of the historical scientific landscape. Overall, current AI research agents appear better suited to local elaboration than to broadening scientific exploration.

Knowledge graphs (KGs) can provide structured scientific context to language models, but it remains unclear which graph facts actually shape the generated hypotheses. We study KG-guided hypothesis generation for battery materials across Mistral-7B, Llama-3.1-70B, and Gemini 2.5 Flash. We perturb local KGs by varying density, ontology richness, topology, and control structure, and evaluate outputs with both provided-graph and fixed-reference metrics. Across models, KG utility is selective and model-dependent: graph context changes outputs, but no-KG outputs also recover substantial graph content from model priors. Compact top-k subgraphs often approximate full-KG behavior, including when claimed-outcome triples are held out. At the same time, compression is not unique to one semantic ranking rule, random and topology-based subsets can also recover much of the signal. These results support a redundancy-aware Compressive KG hypothesis: useful KG signal is often recoverable from compact, scientifically structured subgraphs rather than requiring the full local graph.

Biomedical discovery often requires connecting broad biomedical knowledge with specific experimental or clinical data. Background knowledge suggests relevant mechanisms but is usually too general to map directly onto dataset variables, while data-driven patterns can be dataset-specific and hard to interpret mechanistically. We study this missing link as knowledge contextualization: transforming broad biomedical knowledge into evidence-supported, scenario-grounded propositions that domain experts can inspect, replay, and validate. We propose SCENE, a bi-level multi-agent framework that treats knowledge contextualization as iterative search. The upper level converts broad knowledge into search directions and grounds them in the dataset schema. The lower level executes these directions through multi-objective optimization to identify concrete propositions that balance evidential strength and data support. Feedback between the two levels progressively refines the search. We evaluate SCENE in two settings: discovering patient subgroups with heterogeneous treatment benefits in clinical trial scenarios, and identifying context-specific biological responses in LINCS L1000 studies. In clinical trials, SCENE discovers specific, well-supported subgroups and outperforms existing baselines. In L1000 studies, SCENE identifies perturbational contexts with strong target-response matching and high positive rates. These results show that SCENE bridges broad knowledge and scenario-specific evidence, producing traceable, inspectable hypotheses for follow-up validation.

Real world decision-making requires constructing mental models under uncertainty over evidence, over the underlying causal rules, and over the state of the world itself. Which computational principles underpin human inference under such conditions, and do LLM-based agents exhibit similar behavior given matching constraints? We address these questions using an inductive inference Box Task in which participants, human children and LLM-based agents, infer a latent cause through sequential interaction with an uncertain environment. We formalize this task as program induction with Bayesian particle-based inference, admitting two complementary interpretations: (1) as a constraint satisfaction process over hypotheses, and (2) as a program synthesis problem in which hypotheses are executable programs evaluated against evidence. Using the constraint-based formulation, we show that children's behavior is best explained by a combination of subjective evidence reliability and online hypothesis generation, accounting for both their evidence-seeking patterns and their dissociation between task completion and rule generalization. Using the program synthesis formulation, we treat LLM-based agents as model organisms: controllable systems that allow systematic manipulation of task conditions. Across backends, LLM-based agents replicate children's responses to changes in evidence reliability and observability, including discounting unreliable evidence, seeking to resolve partial information, and dissociating between task completion and causal generalization. At the same time, LLM-based agents tend to over-observe and over-comply with instructions relative to children. These results suggest that while children and LLM-based agents adapt similarly to environmental structure, their information-seeking behavior exhibits distinct underlying costs and inductive biases.

Scientific discovery is a closed-loop process in which hypotheses guide data acquisition and observations refine the hypothesis space. Yet most approaches reduce discovery to supervised learning over fixed datasets, where limited observations can support multiple plausible mechanisms that fit locally but fail to generalize. Thus, the key challenge is selecting informative observations to resolve uncertainty, shifting the focus from static inference to adaptive data acquisition. To address this, we propose LLM-AutoSciLab, a closed-loop framework that couples hypothesis generation with hypothesis-conditioned experiment selection and mechanism refinement. Rather than fitting models to passively collected data, LLM-AutoSciLab iteratively proposes plausible hypotheses, selects informative experiments to distinguish or refine them, and updates its state using the resulting evidence. To evaluate dynamic, closed-loop scientific discovery with active data acquisition, we introduce ActiveSciBench, comprising two datasets: ActiveSciBench-Chem with 57 enzyme-kinetics tasks and ActiveSciBench-GRN with 45 gene-regulatory-network tasks. These datasets model discovery as a budget-constrained process requiring adaptive experiment design, variable selection, and recovery of true mechanisms. Across NewtonBench, ActiveSciBench-Chem, and ActiveSciBench-GRN, LLM-AutoSciLab outperforms prior methods, achieving 67.6% and 35.1% symbolic accuracy on NewtonBench and ActiveSciBench-Chem, respectively, and 31.1% exact graph recovery on ActiveSciBench-GRN. Moreover, hypothesis-guided experimentation is 2-5x more sample-efficient than the strongest competing baselines. Code and data are available at: https://github.com/scientific-discovery/LLM-AutoSciLab

Large language models (LLMs), have shown strong potential in scientific discovery, yet existing methods still face substantial challenges in the design of research workflows and multi-role collaboration mechanisms. To mitigate these issues, we propose EvoSci, a multi-agent scientific collaboration framework, which integrates bio-inspired evolution with knowledge graph modeling. To iteratively generate, evaluate, and refine research ideas, EvoSci incorporates multiple role-based agents, including mentor, researcher, and reviewer. By combining collaborative reasoning, shared memory, and evolutionary feedback, EvoSci significantly enhances the coherence and creativity of scientific exploration. Experiments on real-world research topics demonstrate that EvoSci significantly outperforms strong baselines in LLM-based structured peer-review and comparative ranking evaluations, achieving the highest overall peer-review score (ICLR 4.90) and top ranking (Top-10 = 54). These results suggest its superiority in both scientific idea generation and continuous discovery.

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.

Research idea generation is the innovation-driving step of automated scientific research. Recently, large language models (LLMs) have shown potential for automating idea generation at scale. However, existing methods mainly condition LLMs on eliciting idea generation through static retrieval of relevant literature or complex prompt engineering, without discarding the structural relations among references. We propose Graphs of Research (GoR), a supervised fine-tuning method that extracts a 2-hop reference neighborhood for each seed paper, derives the relations among those references from citation position, frequency, predecessor links, and publication time, and organizes them into a paper-evolution directed acyclic graph (DAG). We construct an automated extraction pipeline that draws data from five major ML/NLP venues, comprising 498/50/50 train/validation/test seed papers and approximately 7,600 cited references. Qwen2.5-7B-Instruct-1M is fine-tuned on a structured-text prompt that includes the citation graph, edge signals, reference information, and task definition to predict the idea for the seed paper. Across head-to-head LLM-judge tournaments against gpt-4o-driven baselines, GoR-SFT achieves SOTA, demonstrating the effectiveness of citation-evolution graphs as supervision signal for LLM-based idea generation. We hope that this reduces the barrier for citation evolution graphs as a supervision, accelerating automated scientific innovation.

As artificial intelligence advances, models are not improving uniformly. Instead, progress unfolds in a jagged fashion, with capabilities growing unevenly across tasks, domains, and model scales. In this work, we examine this dynamic jaggedness through the lens of scientific idea generation. We introduce SciAidanBench, a benchmark of open-ended scientific questions designed to measure the scientific creativity of large language models (LLMs). Given a scientific question, models are asked to generate as many unique and coherent ideas as possible, with the total number of valid responses serving as a proxy for creative potential. Evaluating 19 base models across 8 providers (30 total variants including reasoning versions), we find that jaggedness manifests both across models and within models. First, in a cross-task comparison between general and scientific creativity, improvements in general creativity do not translate uniformly to scientific creativity, revealing divergent capability profiles across models. Second, at the prompt level, stronger models do not improve uniformly; instead, they exhibit high variability, with bursts of creativity on some questions and limited performance on others. Third, at the domain level, individual models display uneven strengths across scientific subfields, reflecting fragmented internal capability profiles. Finally, we show that this jaggedness can be harnessed. We explore mechanisms of inference-time compute, knowledge pooling, and brainstorming to combine models effectively and construct meta-model ensembles that outperform any single model. Our results position jaggedness not as a limitation, but as a resource, a structural feature of AI progress that, when understood and leveraged, can amplify LLM-driven scientific creativity.

A growing body of work pursues AI scientists capable of end-to-end autonomous scientific discovery. This position paper argues that although they already function as co-scientists, agentic AI scientists are not built for autonomous scientific discovery. We identify the following challenges in building and deploying autonomous AI scientists: (1) Problem selection is influenced by the McNamara fallacy; (2) Agents are built on large language models (LLMs) whose training corpora omit tacit procedural and failure knowledge of laboratory practice; (3) Preference optimisation during post-training compresses output diversity toward consensus; and (4) Most scientific benchmarks measure single-turn prediction accuracy and lack feedback from physical experiments back to the computational model. These challenges are not just questions of scale and scaffolding; they require revisiting fundamental design choices. To build truly autonomous AI scientists, we recommend the use of scientific simulations as verifiers for training, the design of persistent world models that represent the shifting objectives governing real investigations, the establishment of a centralized preregistration repository for all AI-generated hypotheses, and application driven by scientific need rather than tool affordance.

Autonomous experimentation has transformed microscopy and materials discovery by enabling closed-loop optimization including imaging and spectroscopy tuning, strucutre property relationship discovery, and exploration of combinatorial libraries. However, most current workflows remain limited to selecting measurements within fixed objective or hypothesis spaces, rather than generating new physical models from experimental data. Here, we introduce an open hypothesis-learning framework that combines symbolic regression with large-language-model-based physical evaluation and implement it for autonomous scanning probe microscopy. Symbolic regression generates candidate analytical relationships directly from sparse measurements, while the language-model evaluator ranks these candidates according to physical plausibility, scaling behavior, and consistency with known mechanisms. We demonstrate the approach on autonomous piezoresponse force microscopy measurements of ferroelectric domain switching in a PZT thin film. Starting from five seed measurements, the workflow evolves from physically incomplete candidate expressions toward interpretable voltage-time growth laws consistent with kinetic domain-wall motion. This work extends autonomous microscopy from closed-loop optimization toward open hypothesis discovery, where candidate physical laws emerge from the experiment itself rather than being specified in advance. More broadly, the framework establishes a route for integrating symbolic regression, physical reasoning, and adaptive experimentation into hierarchical autonomous scientific workflows.

AI research agents have shown strong potential in automating literature search and manuscript refinement, yet most assume a clear and actionable initial input, operating only after a research question has been made explicit. In contrast, human research often begins with tacit friction, a sense of misalignment before a question can be formed. We introduce InciteResearch, a multi-agent framework designed to make a researcher's implicit understanding explicit, inspectable, and actionable. InciteResearch decomposes the logical chain of Socratic questioning and distributes it across the entire pipeline that: (1) Elicits a structured five-dimensional researcher profile state anchored by specific friction points from vague, even domain-unrelated inputs; (2) Violates hidden assumptions by maximizing the feasibility-novelty product with enforcing a 7-stage causal derivation trace; and (3) check whether the proposed method is a Necessary consequence of the reframed insight. We further introduce TF-Bench, the first benchmark for tacit-to-explicit research assistance that distinguishes domain-related from domain-unrelated inspirations across four scientific modes. On TF-Bench, InciteResearch achieves leapfrogging gains over a prompt-based baseline (novelty/impact from 3.671/3.806 to 4.250/4.397), shifting generated proposals from recombination to architectural insight. Our work demonstrates that AI can serve as an extension of thinking itself, rather than merely automating downstream execution.

Large language models (LLMs) increasingly help people solve problems, from debugging code to repairing machinery. This process requires generating plausible hypotheses from partial descriptions, then updating them as more information arrives. Yet how LLMs perform this form of inference, and how close it is to optimal, remains unclear. We study this question in the number game, a controlled setting in which a learner infers the hypothesis supported by a few positive integers, such as $\{16, 8, 2, 64\}$: a rule like powers of 2 or an interval like numbers near 20. We measure the posterior over hypotheses using three complementary probes: posterior prediction, hypothesis evaluation, and hypothesis generation. We then compare LLM behavior with an optimal Bayesian model and human behavior, and test whether the same posterior is expressed across probes. LLMs are often well described by a two-parameter Bayesian fit, but with systematic offsets: by default they show a strong-sampling assumption that creates an implicit Occam's razor, favoring narrower hypotheses, while thinking mode shifts them toward greater prior reliance. We also find a robust evaluation--generation gap: LLMs select more correct hypotheses during hypothesis evaluation but generate simpler, more rule-like hypotheses. Finally, this Bayesian-with-bias pattern does not extrapolate. Models can behave as if they hold rule-like hypotheses over observed examples, yet generalize poorly to parts of the hypothesis domain not covered by those examples. Our results highlight a limitation of LLMs as general problem solvers, especially for scientific inference, where hypotheses must go beyond the data.

LLM-empowered multi-agent systems offer new potential to accelerate scientific discovery by generating novel research ideas. However, existing methods typically coordinate agents through temporary texts, such as drafts or chat logs; it is difficult to pinpoint the weaknesses in the generated ideas and how the agents refine them. To this end, we introduce \textbf{Evolving Idea Graphs} (EIG), a graph-based multi-agent scientific ideation framework that can generate high-performance research ideas across various benchmark-native metrics, such as novelty, feasibility, and clarity. Instead of coordinating solely through texts, EIG represents a partially formed proposal as an evolving idea graph, where nodes capture scientific claims and edges encode relations (e.g., support and conflict), enabling unresolved weaknesses to remain identifiable throughout the idea evolving process. Specifically, a learned two-head controller operates over the evolving graph to guide the ideation: one head selects graph edits for agents to execute, while the other decides when the graph is ready for commit as final proposal synthesis. On AI Idea Bench 2025 and LiveIdeaBench, EIG outperforms all compared systems on both automatic benchmark scores and blind expert ratings. Ablations further show that explicit graph state provides the main performance gains, and learned edit-and-commit control adds consistent improvements.

Drug-induced liver injury (DILI) remains a leading cause of late-stage clinical trial attrition. However, existing computational predictors primarily rely on binary classification, a framing that limits generalization and yields no mechanistic insight to guide translational decisions. We argue that DILI prediction is better posed as an explainable hypothesis-generation problem. To support this shift, we introduce the DILER Benchmark, a dataset that extends beyond binary labels by augmenting a curated set of molecules with mechanistic hepatotoxicity hypotheses derived from biomedical literature. We further present HADES, an agentic system designed to generate transparent and auditable reasoning traces. By combining molecular-level predictions, metabolite decomposition, structural understanding, and toxicity pathway evidence, HADES mechanistically assesses DILI risk. Evaluated on the DILER Benchmark, HADES outperforms existing models in binary classification, achieving a ROC-AUC of 0.68 on the Test Set and 0.59 on the challenging Post-2021 Set, compared with 0.63 and 0.50 for DILI-Predictor, respectively. More importantly, we establish a baseline for mechanistic hypothesis generation, where HADES achieves a Hypothesis Alignment Fuzzy Jaccard Index of 0.16. This result underscores the inherent complexity of the task while highlighting the need for advanced explainable approaches in predictive toxicology.

Scientific discovery is an extended process of ideation--surveying prior work, forming hypotheses, and refining reasoning--yet existing approaches treat this phase as a brief preamble despite its central role in research. We introduce SCISENSE, a sensemaking-grounded framework that operationalizes ideation as a structured sequence of eight cognitive stages (Pirolli & Card, 2005). We construct SCISENSE-Traj, a 100K-scale dataset of citation-conditioned research trajectories in two modes: Target, where an LLM reconstructs the ideation path leading to a known paper from its cited works, and Infer, where the LLM proposes novel directions from the same citations. We distill these into SCISENSE-LM, a family of sensemaking LLMs spanning 3B to 70B parameters. Contrary to the assumption that looser supervision promotes greater exploration, Target-trained models achieve a 2.0% improvement in trajectory quality over Infer-trained models while also producing more novel and diverse outputs. This advantage propagates downstream: coding agents conditioned on Target trajectories produce research artifacts with higher executability and quality than those conditioned on Infer trajectories. This suggests that targeted ideation reduces cognitive burden on downstream agents, freeing them to explore more creatively. SCISENSE offers both a practical tool for augmenting LLM-driven research workflows and a principled testbed for studying how planning shapes scientific discovery.

Current knowledge graph (KG) construction methods are confirmatory, focusing on recovering known relationships rather than identifying novel or context-dependent nodes. This paper proposes a phenotype-driven and evidence-governed framework that shifts the paradigm toward structured hypothesis discovery and controlled KG expansion. The approach integrates graph neural networks (GNNs) for phenotype discovery, causal inference, probabilistic reasoning and large language models (LLMs) for hypothesis generation and claim extraction within a unified pipeline. The framework prioritizes relationships that are both structurally supported by data and underexplored in the literature. KG expansion is formulated as a multi-objective optimization problem, where candidate claims are jointly evaluated in terms of relevance, structural validation and novelty. Pareto-optimal selection enables the identification of non-dominated claims that balance confirmation and discovery, avoiding trivial or redundant knowledge inclusion. Experiments on heterogeneous population datasets demonstrate that the proposed framework produces more interpretable phenotypes, reveals context-dependent causal structures and generates high-quality claims that align with both data and scientific evidence. Compared to rule-based and LLM-only baselines, the method achieves the best trade-off across plausibility, novelty, validation and relevance. In retrieval-augmented settings, it significantly improves performance (Recall@5=0.98) while reducing hallucination rates (0.05), highlighting its effectiveness in grounding LLM outputs.