Gabriele Scalia
Publications
LLM-Guided Retrieval for Prediction of Molecular Perturbation Responses
Predicting transcriptomic responses to small-molecule perturbations across cell lines is central to drug discovery, but exhaustive profiling of drug-cell combinations is infeasible. We frame molecular perturbation prediction as retrieve-and-aggregate: approximate an unmeasured drug's response in a cell line by aggregating measured responses of a small set of biologically related compounds. We propose LLM-Guided Retrieval (LGR), where a large language model (LLM) ranks candidate neighbor drugs (restricted to those profiled in the target cell line); after which a fixed mean aggregator combines their observed expression deltas to form the prediction. We evaluate on the Tahoe-100M single-cell perturbation atlas under unseen-drug, unseen-cell-line, and open-world regimes. LGR consistently improves over drug mean, ChemCPA, and chemistry-based kNN baselines, with the strongest gains for unseen cell-line generalization, where it achieves higher correlation and lower error than mean baselines. Across settings, LGR improves directional (sign) accuracy of gene regulation, indicating better recovery of biologically meaningful perturbation effects even when magnitude-based metrics are similar. These results suggest that retrieval quality, rather than predictor complexity, is a key driver of zero-shot molecular perturbation prediction, and that LLMs can provide a useful biological prior when used as constrained retrieval modules.
DC-W2S: Dual-Consensus Weak-to-Strong Training for Reliable Process Reward Modeling in Biological Reasoning
In scientific reasoning tasks, the veracity of the reasoning process is as critical as the final outcome. While Process Reward Models (PRMs) offer a solution to the coarse-grained supervision problems inherent in Outcome Reward Models (ORMs), their deployment is hindered by the prohibitive cost of obtaining expert-verified step-wise labels. This paper addresses the challenge of training reliable PRMs using abundant but noisy "weak" supervision. We argue that existing Weak-to-Strong Generalization (W2SG) theories lack prescriptive guidelines for selecting high-quality training signals from noisy data. To bridge this gap, we introduce the Dual-Consensus Weak-to-Strong (DC-W2S) framework. By intersecting Self-Consensus (SC) metrics among weak supervisors with Neighborhood-Consensus (NC) metrics in the embedding space, we stratify supervision signals into distinct reliability regimes. We then employ a curriculum of instance-level balanced sampling and label-level reliability-aware masking to guide the training process. We demonstrate that DC-W2S enables the training of robust PRMs for complex reasoning without exhaustive expert annotation, proving that strategic data curation is more effective than indiscriminate training on large-scale noisy datasets.