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Rogier Hintzen

Publications and source records attributed to Rogier Hintzen.

2 recordsLinked to original sources

Tiny Moves: Game-based Hypothesis Refinement

Most machine learning approaches to scientific discovery frame hypotheses as end-to-end predictions, obscuring the incremental structure of scientific reasoning. We propose The Hypothesis Game, a symbolic formalism for hypothesis refinement in which LLM agents operate on a shared hypothesis state using a fixed grammar of reasoning moves. The framework is motivated by the observation that scientific progress often proceeds through small, localized revisions, grounded in domain context, rather than extensive rewrites. We instantiate a minimal game with LLM agents and evaluate it on pathway-level mechanistic refinement tasks. In the primary setting of corruption recovery, where hypotheses contain controlled errors, the game-based approach consistently removes more errors and achieves higher precision than strong prompting baselines, while preserving valid structure through incremental edits. In a secondary reconstruction setting from partial cues, it performs comparably to the strongest baseline, indicating that explicit move-based refinement remains competitive even when ground-truth recovery is difficult. These findings support game-based reasoning as a principled route to more controllable, interpretable, and transferable hypothesis refinement systems for scientific discovery.

cs.MA

Retrieve to Explain: Evidence-driven Predictions for Explainable Drug Target Identification

Language models hold incredible promise for enabling scientific discovery by synthesizing massive research corpora. Many complex scientific research questions have multiple plausible answers, each supported by evidence of varying strength. However, existing language models lack the capability to quantitatively and faithfully compare answer plausibility in terms of supporting evidence. To address this, we introduce Retrieve to Explain (R2E), a retrieval-based model that scores and ranks all possible answers to a research question based on evidence retrieved from a document corpus. The architecture represents each answer only in terms of its supporting evidence, with the answer itself masked. This allows us to extend feature attribution methods such as Shapley values, to transparently attribute answer scores to supporting evidence at inference time. The architecture also allows incorporation of new evidence without retraining, including non-textual data modalities templated into natural language. We developed R2E for the challenging scientific discovery task of drug target identification, a human-in-the-loop process where failures are extremely costly and explainability paramount. When predicting whether drug targets will subsequently be confirmed as efficacious in clinical trials, R2E not only matches non-explainable literature-based models but also surpasses a genetics-based target identification approach used throughout the pharmaceutical industry.

cs.LG