arXiv subjects

Aristofanis Rontogiannis

Publications and source records attributed to Aristofanis Rontogiannis.

3 recordsLinked to original sources

arXiv2026

PairSAE: Mechanistic Interpretability from Pair Representations in Protein Co-Folding

Foundation models for structural biology have achieved remarkable performance in predicting biomolecular structure and show promise for the design of proteins and small molecules. Yet understanding which internal features drive their outputs remains challenging. Standard sparse autoencoders (SAEs), effective on transformer-style sequence embeddings, do not transfer cleanly to pairformer-like architectures: naively operating on pairwise representations yields a quadratic blow-up of features and obscures concepts distributed jointly across sequence and pair representations. We introduce PairSAE, which summarizes pairwise tensors via an N-mode SVD into token-wise interaction roles, then uses a sparse autoencoder to learn a shared set of token-level features that decode into both sequence and pair representations. Evaluated on Boltz-2 activations for PLINDER protein-ligand complexes, PairSAE yields interpretable features that align with UniProt annotations and predict Boltz-2 affinity values. These results indicate that PairSAE links the latent space of foundation models for structural biology to interpretable structural concepts, clarifying what the model "knows" while avoiding pairformer-induced pitfalls that limit conventional SAEs.

cs.LG↗

arXiv2025

Robustness intervals for competing risks analysis with causes of failure missing not at random

Analysis of competing risks data is often complicated by the incomplete or selectively missing information on the cause of failure. Standard approaches typically assume that the cause of failure is missing at random (MAR), an assumption that is generally untestable and frequently implausible in observational studies. We propose a novel sensitivity analysis framework for the proportional cause-specific hazards model that accommodates missing-not-at-random (MNAR) scenarios. A sensitivity parameter is used to quantify the association between missingness and the unobserved cause of failure. Regression coefficients are estimated as functions of this parameter, and a simultaneous confidence band is constructed via a wild bootstrap procedure. This allows identification of a range of MNAR scenarios for which effects remain statistically significant; we refer to this range as a robustness interval. The validity of the proposed approach is justified both theoretically, via empirical process theory, and empirically, through simulation studies. We apply the method to the analysis of data from an HIV cohort study in sub-Saharan Africa, where a substantial proportion of causes of failure are missing and the MAR assumption is implausible. The analysis shows that key findings regarding risk factors for care interruption and mortality are robust across a broad spectrum of MNAR scenarios, underscoring the method's utility in situations with MNAR causes of failure.

stat.ME↗

arXiv2025

Relaxed Sequence Sampling for Diverse Protein Design

Protein design using structure prediction models such as AlphaFold2 has shown remarkable success, but existing approaches like relaxed sequence optimization (RSO) rely on single-path gradient descent and ignore sequence-space constraints, limiting diversity and designability. We introduce Relaxed Sequence Sampling (RSS), a Markov chain Monte Carlo (MCMC) framework that integrates structural and evolutionary information for protein design. RSS operates in continuous logit space, combining gradient-guided exploration with protein language model-informed jumps. Its energy function couples AlphaFold2-derived structural objectives with ESM2-derived sequence priors, balancing accuracy and biological plausibility. In an in silico protein binder design task, RSS produces 5$\times$ more designable structures and 2-3$\times$ greater structural diversity than RSO baselines, at equal computational cost. These results highlight RSS as a principled approach for efficiently exploring the protein design landscape.

cs.LG↗