Daniel Rose

Daniel Rose, Oliver Wieder, Thomas Seidel et al.

The increasing size of screening libraries poses a significant challenge for the development of virtual screening methods for drug discovery, necessitating a re-evaluation of traditional approaches in the era of big data. Although 3D pharmacophore screening remains a prevalent technique, its application to very large datasets is limited by the computational cost associated with matching query pharmacophores to database molecules. In this study, we introduce PharmacoMatch, a novel contrastive learning approach based on neural subgraph matching. Our method reinterprets pharmacophore screening as an approximate subgraph matching problem and enables efficient querying of conformational databases by encoding query-target relationships in the embedding space. We conduct comprehensive investigations of the learned representations and evaluate PharmacoMatch as pre-screening tool in a zero-shot setting. We demonstrate significantly shorter runtimes and comparable performance metrics to existing solutions, providing a promising speed-up for screening very large datasets.

Daniel Rose, Chia-Chien Hung, Marco Lepri et al.

Differential Diagnosis (DDx) is a fundamental yet complex aspect of clinical decision-making, in which physicians iteratively refine a ranked list of possible diseases based on symptoms, antecedents, and medical knowledge. While recent advances in large language models (LLMs) have shown promise in supporting DDx, existing approaches face key limitations, including single-dataset evaluations, isolated optimization of components, unrealistic assumptions about complete patient profiles, and single-attempt diagnosis. We introduce a Modular Explainable DDx Agent (MEDDxAgent) framework designed for interactive DDx, where diagnostic reasoning evolves through iterative learning, rather than assuming a complete patient profile is accessible. MEDDxAgent integrates three modular components: (1) an orchestrator (DDxDriver), (2) a history taking simulator, and (3) two specialized agents for knowledge retrieval and diagnosis strategy. To ensure robust evaluation, we introduce a comprehensive DDx benchmark covering respiratory, skin, and rare diseases. We analyze single-turn diagnostic approaches and demonstrate the importance of iterative refinement when patient profiles are not available at the outset. Our broad evaluation demonstrates that MEDDxAgent achieves over 10% accuracy improvements in interactive DDx across both large and small LLMs, while offering critical explainability into its diagnostic reasoning process.

Daniel Rose, Roxane Axel Jacob, Johannes Kirchmair et al.

Transformer-based autoregressive models offer a promising alternative to diffusion- and flow-matching approaches for generating 3D molecular structures. However, standard transformer architectures require a sequential ordering of tokens, which is not uniquely defined for the atoms in a molecule. Prior work has addressed this by using canonical atom orderings, but these do not ensure permutation invariance of atoms, which is essential for tasks like prefix completion. We introduce NEAT, a Neighborhood-guided, Efficient, Autoregressive, Set Transformer that treats molecular graphs as sets of atoms and learns an order-agnostic distribution over admissible tokens at the graph boundary. NEAT achieves state-of-the-art performance in autoregressive 3D molecular generation whilst ensuring atom-level permutation invariance by design.

Vaishnavi Himakunthala, Andy Ouyang, Daniel Rose et al.

Despite exciting recent results showing vision-language systems' capacity to reason about images using natural language, their capacity for video reasoning remains under-explored. We motivate framing video reasoning as the sequential understanding of a small number of keyframes, thereby leveraging the power and robustness of vision-language while alleviating the computational complexities of processing videos. To evaluate this novel application, we introduce VIP, an inference-time challenge dataset designed to explore models' reasoning capabilities through video chain-of-thought. Inspired by visually descriptive scene plays, we propose two formats for keyframe description: unstructured dense captions and structured scene descriptions that identify the focus, action, mood, objects, and setting (FAMOuS) of the keyframe. To evaluate video reasoning, we propose two tasks: Video Infilling and Video Prediction, which test abilities to generate multiple intermediate keyframes and predict future keyframes, respectively. We benchmark GPT-4, GPT-3, and VICUNA on VIP, demonstrate the performance gap in these complex video reasoning tasks, and encourage future work to prioritize language models for efficient and generalized video reasoning.

Daniel Rose, Vaishnavi Himakunthala, Andy Ouyang et al.

Recent advances in large language models elicit reasoning in a chain-of-thought that allows models to decompose problems in a human-like fashion. Though this paradigm improves multi-step reasoning ability in language models, it is limited by being unimodal and applied mainly to question-answering tasks. We claim that incorporating visual augmentation into reasoning is essential, especially for complex, imaginative tasks. Consequently, we introduce VCoT, a novel method that leverages chain-of-thought prompting with vision-language grounding to recursively bridge the logical gaps within sequential data. Our method uses visual guidance to generate synthetic multimodal infillings that add consistent and novel information to reduce the logical gaps for downstream tasks that can benefit from temporal reasoning, as well as provide interpretability into models' multi-step reasoning. We apply VCoT to the Visual Storytelling and WikiHow summarization datasets and demonstrate through human evaluation that VCoT offers novel and consistent synthetic data augmentation beating chain-of-thought baselines, which can be used to enhance downstream performance.