相关论文: Decomposing the Generalization Gap in PROTAC Activ…

PROTACs are a promising therapeutic modality that harnesses the cell's built-in degradation machinery to degrade specific proteins. Despite their potential, developing new PROTACs is challenging and requires significant domain expertise,…

Proteolysis-targeting chimeras (PROTACs) represent a promising therapeutic modality that induces targeted protein degradation by hijacking the ubiquitin-proteasome system. However, rational PROTAC design remains challenging due to the…

PROteolysis TArgeting Chimeras (PROTACs) are an emerging therapeutic modality for degrading a protein of interest (POI) by marking it for degradation by the proteasome. Recent developments in artificial intelligence (AI) suggest that deep…

Proteolysis targeting chimeras (PROTACs) are small molecules that trigger the breakdown of traditionally ``undruggable'' proteins by binding simultaneously to their targets and degradation-associated proteins. A key challenge in their…

Targeted protein degradation (TPD) is a rapidly growing field in modern drug discovery that aims to regulate the intracellular levels of proteins by harnessing the cell's innate degradation pathways to selectively target and degrade…

Activation functions play an important role in training artificial neural networks. The majority of currently used activation functions are deterministic in nature, with their fixed input-output relationship. In this work, we propose a…

Language generation maps a rich, high-dimensional internal state to a single token sequence. We study this many-to-one mapping through the lens of intention collapse: the projection from an internal intention space I to an external language…

Adversarially trained models exhibit a large generalization gap: they can interpolate the training set even for large perturbation radii, but at the cost of large test error on clean samples. To investigate this gap, we decompose the test…

In the era of AI-driven science and engineering, we often want to design discrete objects in silico according to user-specified properties. For example, we may wish to design a protein to bind its target, arrange components within a circuit…

Most uncertainty-aware robotic systems collapse prediction uncertainty into a single scalar score and use it to trigger uniform corrective responses. This aggregation obscures whether uncertainty arises from corrupted observations or from…

As machine learning becomes increasingly central to molecular design, it is vital to ensure the reliability of learnable protein-ligand scoring functions on novel protein targets. While many scoring functions perform well on standard…

Despite the efficacy of Direct Preference Optimization (DPO) in aligning Large Language Models (LLMs), reward hacking remains a pivotal challenge. This issue emerges when LLMs excessively reduce the probability of rejected completions to…

Linear probes can detect when language models produce outputs they "know" are wrong, a capability relevant to both deception and reward hacking. However, single-layer probes are fragile: the best layer varies across models and tasks, and…

In mammalian and vertebrate genomes, the promoter regions of the gene and their distal enhancers may be located millions of base-pairs from each other, while a promoter may not interact with the closest enhancer. Since base-pair proximity…

The ability to detect out-of-distribution (OOD) inputs is fundamental to safe deployment of machine learning systems. Yet, current methods often rely on feature representations that are optimised solely for classification accuracy,…

When evaluating the performance of clinical machine learning models, one must consider the deployment population. When the population of patients with observed labels is only a subset of the deployment population (label selection), standard…

Predictive models in biomedicine depend on structured assay data locked in the text, tables, and supplements of primary publications. This bottleneck is especially acute in targeted protein degradation (TPD), where each assay record must…

LoRA-based continual learning represents a promising avenue for leveraging pre-trained models in downstream continual learning tasks. Recent studies have shown that orthogonal LoRA tuning effectively mitigates forgetting. However, this work…

Linear probes trained on LLM activations are increasingly proposed as deception-detection metrics, yet report AUROC exceeding 0.96 on clean benchmarks while collapsing under distributional shift. This paper systematically pressure-tests…

Out-of-distribution (OOD) detection is critical in safety-sensitive applications. While this challenge has been addressed from various perspectives, the influence of training objectives on OOD behavior remains comparatively underexplored.…