Scalable and Interpretable Representation Alignment with Ordinal Similarity

Evaluating representation similarity is fundamental to representation learning. However, existing metrics suffer from significant limitations: they lack interpretability due to shifting baselines, lack robustness to outliers, and are computationally intractable for large datasets, forcing reliance on heuristic approximations. To address this, we develop an ordinal-similarity framework, instantiated by the Triplet (TSI) and Quadruplet (QSI) Similarity Indices, which measure alignment by quantifying the consistency of ordinal relationships. We theoretically demonstrate this formulation is inherently interpretable, robust to outliers, and computationally efficient. Finally, we establish a formal equivalence between TSI and local neighborhood alignment, measured by Mutual Nearest Neighbors. Empirically, we validate these properties and show that ordinal similarity offers a scalable approach to measuring alignment, enabling practitioners to better understand and design representations.

Sample Efficient Generative Molecular Optimization with Joint Self-Improvement

Generative molecular optimization aims to design molecules with properties surpassing those of existing compounds. However, such candidates are rare and expensive to evaluate, yielding sample efficiency essential. Additionally, surrogate models introduced to predict molecule evaluations, suffer from distribution shift as optimization drives candidates increasingly out-of-distribution. To address these challenges, we introduce Joint Self-Improvement, which benefits from (i) a joint generative-predictive model and (ii) a self-improving sampling scheme. The former aligns the generator with the surrogate, alleviating distribution shift, while the latter biases the generative part of the joint model using the predictive one to efficiently generate optimized molecules at inference-time. Experiments across offline and online molecular optimization benchmarks demonstrate that Joint Self-Improvement outperforms state-of-the-art methods under limited evaluation budgets.

seqme: a Python library for evaluating biological sequence design

Recent advances in computational methods for designing biological sequences have sparked the development of metrics to evaluate these methods performance in terms of the fidelity of the designed sequences to a target distribution and their attainment of desired properties. However, a single software library implementing these metrics was lacking. In this work we introduce seqme, a modular and highly extendable open-source Python library, containing model-agnostic metrics for evaluating computational methods for biological sequence design. seqme considers three groups of metrics: sequence-based, embedding-based, and property-based, and is applicable to a wide range of biological sequences: small molecules, DNA, ncRNA, mRNA, peptides and proteins. The library offers a number of embedding and property models for biological sequences, as well as diagnostics and visualization functions to inspect the results. seqme can be used to evaluate both one-shot and iterative computational design methods.

Unified Molecule Generation and Property Prediction

Modeling the joint distribution of the data samples and their properties allows to construct a single model for both data generation and property prediction, with synergistic capabilities reaching beyond purely generative or predictive models. However, training joint models presents daunting architectural and optimization challenges. Here, we propose Hyformer, a transformer-based joint model that successfully blends the generative and predictive functionalities, using an alternating attention mask together with a unified pre-training scheme. We show that Hyformer rivals other joint models, as well as state-of-the-art molecule generation and property prediction models. Additionally, we show the benefits of joint modeling in downstream tasks of molecular representation learning, hit identification and antimicrobial peptide design.