Kaspar Martens

h-index116
2papers

2 Papers

AISep 2, 2025
Towards Agents That Know When They Don't Know: Uncertainty as a Control Signal for Structured Reasoning

Josefa Lia Stoisser, Marc Boubnovski Martell, Lawrence Phillips et al.

Large language model (LLM) agents are increasingly deployed in structured biomedical data environments, yet they often produce fluent but overconfident outputs when reasoning over complex multi-table data. We introduce an uncertainty-aware agent for query-conditioned multi-table summarization that leverages two complementary signals: (i) retrieval uncertainty--entropy over multiple table-selection rollouts--and (ii) summary uncertainty--combining self-consistency and perplexity. Summary uncertainty is incorporated into reinforcement learning (RL) with Group Relative Policy Optimization (GRPO), while both retrieval and summary uncertainty guide inference-time filtering and support the construction of higher-quality synthetic datasets. On multi-omics benchmarks, our approach improves factuality and calibration, nearly tripling correct and useful claims per summary (3.0\(\rightarrow\)8.4 internal; 3.6\(\rightarrow\)9.9 cancer multi-omics) and substantially improving downstream survival prediction (C-index 0.32\(\rightarrow\)0.63). These results demonstrate that uncertainty can serve as a control signal--enabling agents to abstain, communicate confidence, and become more reliable tools for complex structured-data environments.

GNJul 1, 2025
Modeling Gene Expression Distributional Shifts for Unseen Genetic Perturbations

Kalyan Ramakrishnan, Jonathan G. Hedley, Sisi Qu et al.

We train a neural network to predict distributional responses in gene expression following genetic perturbations. This is an essential task in early-stage drug discovery, where such responses can offer insights into gene function and inform target identification. Existing methods only predict changes in the mean expression, overlooking stochasticity inherent in single-cell data. In contrast, we offer a more realistic view of cellular responses by modeling expression distributions. Our model predicts gene-level histograms conditioned on perturbations and outperforms baselines in capturing higher-order statistics, such as variance, skewness, and kurtosis, at a fraction of the training cost. To generalize to unseen perturbations, we incorporate prior knowledge via gene embeddings from large language models (LLMs). While modeling a richer output space, the method remains competitive in predicting mean expression changes. This work offers a practical step towards more expressive and biologically informative models of perturbation effects.