MolRGen: A Training and Evaluation Setting for De Novo Molecular Generation with Reasonning Models

Recent advances in reasoning-based large language models (LLMs) have demonstrated substantial improvements in complex problem-solving tasks. Motivated by these advances, several works have explored the application of reasoning LLMs to drug discovery and molecular design. However, most existing approaches either focus on evaluation or rely on training setups that require ground-truth labels, such as molecule pairs with known property modifications. Such supervision is unavailable in \textit{de novo} molecular generation, where the objective is to generate novel molecules that optimize a desirability score without prior knowledge of high-scoring candidates. To bridge this gap, we introduce MolRGen, a large-scale benchmark and dataset for training and evaluating reasoning-based LLMs on \textit{de novo} molecular generation. Our contributions are threefold. First, we propose a setting to evaluate and train models for \textit{de novo} molecular generation and property prediction. Second, we introduce a novel diversity-aware top-$k$ score that captures both the quality and diversity of generated molecules. Third, we show our setting can be used to train LLMs for molecular generation, training a 24B LLM with reinforcement learning, and we provide a detailed analysis of its performance and limitations.

Statistical Deficiency for Task Inclusion Estimation

Tasks are central in machine learning, as they are the most natural objects to assess the capabilities of current models. The trend is to build general models able to address any task. Even though transfer learning and multitask learning try to leverage the underlying task space, no well-founded tools are available to study its structure. This study proposes a theoretically grounded setup to define the notion of task and to compute the {\bf inclusion} between two tasks from a statistical deficiency point of view. We propose a tractable proxy as information sufficiency to estimate the degree of inclusion between tasks, show its soundness on synthetic data, and use it to reconstruct empirically the classic NLP pipeline.

Membership Inference Risks in Quantized Models: A Theoretical and Empirical Study

Quantizing machine learning models has demonstrated its effectiveness in lowering memory and inference costs while maintaining performance levels comparable to the original models. In this work, we investigate the impact of quantization procedures on the privacy of data-driven models, specifically focusing on their vulnerability to membership inference attacks. We derive an asymptotic theoretical analysis of Membership Inference Security (MIS), characterizing the privacy implications of quantized algorithm weights against the most powerful (and possibly unknown) attacks. Building on these theoretical insights, we propose a novel methodology to empirically assess and rank the privacy levels of various quantization procedures. Using synthetic datasets, we demonstrate the effectiveness of our approach in assessing the MIS of different quantizers. Furthermore, we explore the trade-off between privacy and performance using real-world data and models in the context of molecular modeling.

When is an Embedding Model More Promising than Another?

Embedders play a central role in machine learning, projecting any object into numerical representations that can, in turn, be leveraged to perform various downstream tasks. The evaluation of embedding models typically depends on domain-specific empirical approaches utilizing downstream tasks, primarily because of the lack of a standardized framework for comparison. However, acquiring adequately large and representative datasets for conducting these assessments is not always viable and can prove to be prohibitively expensive and time-consuming. In this paper, we present a unified approach to evaluate embedders. First, we establish theoretical foundations for comparing embedding models, drawing upon the concepts of sufficiency and informativeness. We then leverage these concepts to devise a tractable comparison criterion (information sufficiency), leading to a task-agnostic and self-supervised ranking procedure. We demonstrate experimentally that our approach aligns closely with the capability of embedding models to facilitate various downstream tasks in both natural language processing and molecular biology. This effectively offers practitioners a valuable tool for prioritizing model trials.

Is Meta-training Really Necessary for Molecular Few-Shot Learning ?

Few-shot learning has recently attracted significant interest in drug discovery, with a recent, fast-growing literature mostly involving convoluted meta-learning strategies. We revisit the more straightforward fine-tuning approach for molecular data, and propose a regularized quadratic-probe loss based on the the Mahalanobis distance. We design a dedicated block-coordinate descent optimizer, which avoid the degenerate solutions of our loss. Interestingly, our simple fine-tuning approach achieves highly competitive performances in comparison to state-of-the-art methods, while being applicable to black-box settings and removing the need for specific episodic pre-training strategies. Furthermore, we introduce a new benchmark to assess the robustness of the competing methods to domain shifts. In this setting, our fine-tuning baseline obtains consistently better results than meta-learning methods.

$\texttt{COSMIC}$: Mutual Information for Task-Agnostic Summarization Evaluation

Assessing the quality of summarizers poses significant challenges. In response, we propose a novel task-oriented evaluation approach that assesses summarizers based on their capacity to produce summaries that are useful for downstream tasks, while preserving task outcomes. We theoretically establish a direct relationship between the resulting error probability of these tasks and the mutual information between source texts and generated summaries. We introduce $\texttt{COSMIC}$ as a practical implementation of this metric, demonstrating its strong correlation with human judgment-based metrics and its effectiveness in predicting downstream task performance. Comparative analyses against established metrics like $\texttt{BERTScore}$ and $\texttt{ROUGE}$ highlight the competitive performance of $\texttt{COSMIC}$.