Post-Translational Modifications (PTMs) are changes that occur in proteins after synthesis, influencing their structure, function, and cellular behavior. PTMs are essential in cell biology; they regulate protein function and stability, are involved in various cellular processes, and are linked to numerous diseases. A particularly interesting class of PTMs are chemical modifications such as phosphorylation introduced on amino acid side chains because they can drastically alter the physicochemical properties of the peptides once they are present. One or more PTMs can be attached to each amino acid of the peptide sequence. The most commonly applied technique to detect PTMs on proteins is bottom-up Mass Spectrometry-based proteomics (MS), where proteins are digested into peptides and subsequently analyzed using Tandem Mass Spectrometry (MS/MS).

Before deploying outputs from foundation models in high-stakes tasks, it is imperative to ensure that they align with human values.For instance, in radiology report generation, reports generated by a vision-language model must align with human evaluations before their use in medical decision-making. This paper presents Conformal Alignment, a general framework for identifying units whose outputs meet a user-specified alignment criterion. It is guaranteed that on average, a prescribed fraction of selected units indeed meet the alignment criterion, regardless of the foundation model or the data distribution. Given any pre-trained model and new units with model-generated outputs, Conformal Alignment leverages a set of reference data with ground-truth alignment status to train an alignment predictor. It then selects new units whose predicted alignment scores surpass a data-dependent threshold, certifying their corresponding outputs as trustworthy. Through applications to question answering and radiology report generation, we demonstrate that our method is able to accurately identify units with trustworthy outputs via lightweight training over a moderate amount of reference data. En route, we investigate the informativeness of various features in alignment prediction and combine them with standard models to construct the alignment predictor.

We introduce an extension of the partitioned local depth (PaLD) algorithm that is adapted to online applications such as semi-supervised prediction. The new algorithm we present, online PaLD, is well-suited to situations where it is a possible to pre-compute a cohesion network from a reference dataset. After $O(n^3)$ steps to construct a queryable data structure, online PaLD can extend the cohesion network to a new data point in $O(n^2)$ time. Our approach complements previous speed up approaches based on approximation and parallelism. For illustrations, we present applications to online anomaly detection and semi-supervised classification for health-care datasets.

Environmental modeling faces critical challenges in predicting ecosystem dynamics across unmonitored regions due to limited and geographically imbalanced observation data. This challenge is compounded by spatial heterogeneity, causing models to learn spurious patterns that fit only local data. Unlike conventional domain generalization, environmental modeling must preserve invariant physical relationships and temporal coherence during augmentation. In this paper, we introduce Generalizable Representation Enhancement via Auxiliary Transformations (GREAT), a framework that effectively augments available datasets to improve predictions in completely unseen regions. GREAT guides the augmentation process to ensure that the original governing processes can be recovered from the augmented data, and the inclusion of the augmented data leads to improved model generalization. Specifically, GREAT learns transformation functions at multiple layers of neural networks to augment both raw environmental features and temporal influence. They are refined through a novel bi-level training process that constrains augmented data to preserve key patterns of the original source data. We demonstrate GREAT's effectiveness on stream temperature prediction across six ecologically diverse watersheds in the eastern U.S., each containing multiple stream segments. Experimental results show that GREAT significantly outperforms existing methods in zero-shot scenarios. This work provides a practical solution for environmental applications where comprehensive monitoring is infeasible.

The next lemma characterizes the spectral properties of the disagreement matrix, used in Lemma 4. 18 Lemma 7. W is also a stochastic matrix. W are that of I W, each with multiplicity K . Lemma 8. F or every n > 0 we have null null The next Lemma is a well known bound for functions with Lipschitz gradients. The importance is merely technical, and is meant to compress our set of assumption. The MNIST results in Figure 1 used the same settings as above.

Generative models are increasingly central to scientific workflows, yet their systematic use and interpretation require a proper understanding of their limitations through rigorous validation. Classic approaches struggle with scalability, statistical power, or interpretability when applied to high-dimensional data, making it difficult to certify the reliability of these models in realistic, high-dimensional scientific settings. Here, we propose the use of the New Physics Learning Machine (NPLM), a learning based approach to goodness-of-fit testing inspired by the Neyman-Pearson construction, to test generative networks trained on high-dimensional scientific data. We demonstrate the performance of NPLM for validation in two benchmark cases: generative models trained on mixtures of Gaussian models with increasing dimensionality, and a public end-to-end generator for the Large Hadron Collider called FlashSim, trained on jet data, typical in the field of high-energy physics. We demonstrate that the NPLM can serve as a powerful validation method while also providing a means to diagnose sub-optimally modeled regions of the data.

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.

Evaluating uncertainty is critical for reliable use of Mobile Laser Scanning (MLS) point clouds in many high-precision applications such as Scan-to-BIM, deformation analysis, and 3D modeling. However, obtaining the ground truth (GT) for evaluation is often costly and infeasible in many real-world applications. To reduce this long-standing reliance on GT in uncertainty evaluation research, this study presents a learning-based framework for MLS point clouds that integrates optimal neighborhood estimation with geometric feature extraction. Experiments on a real-world dataset show that the proposed framework is feasible and the XGBoost model delivers fully comparable accuracy to Random Forest while achieving substantially higher efficiency (about 3 times faster), providing initial evidence that geometric features can be used to predict point-level uncertainty quantified by the C2C distance. In summary, this study shows that MLS point clouds' uncertainty is learnable, offering a novel learning-based viewpoint towards uncertainty evaluation research.

Y et, despite this progress, the point clouds acquired by MLS systems operating in real-world environments inevitably contain uncertainty arising from various error sources during acquisition and processing. Although MLS systems have advanced rapidly in both data collection and post-processing, research on uncertainty evaluation has received comparatively less attention and remains underdeveloped (Xu et al., 2025b). From a user's perspective, the quality of point clouds from MLS systems is a critical concern. As the foundational input for many downstream tasks, inadequate assessment of MLS point clouds' quality can easily impact high-precision applications such as navigation and change analysis. This will not only undermine reliability but also result in substantial waste of time and resources, which is unacceptable in real-world applications. There is a clear need for automated and reliable solutions for uncertainty evaluation. In MLS systems, four main categories of error sources contribute to uncertainty: instrumental errors, atmospheric errors, object-and geometry-related errors, and trajectory estimation errors (Habib et al., 2009, Schenk, 2001). Considering the characteristics of these error sources, existing uncertainty evaluation methods can be broadly divided into two categories: forward modeling and backward modeling (Shi et al., 2021). The core idea of forward modeling is grounded in variance-covariance propagation, which involves detailed theoretical analysis of MLS system errors.

Evaluating large language model (LLM) outputs in the legal domain presents unique challenges due to the complex and nuanced nature of legal analysis. Current evaluation approaches either depend on reference data, which is costly to produce, or use standardized assessment methods, both of which have significant limitations for legal applications. Although LLM-as-a-Judge has emerged as a promising evaluation technique, its reliability and effectiveness in legal contexts depend heavily on evaluation processes unique to the legal industry and how trustworthy the evaluation appears to the human legal expert. This is where existing evaluation methods currently fail and exhibit considerable variability. This paper aims to close the gap: a) we break down lengthy responses into 'Legal Data Points' (LDPs), self-contained units of information, and introduce a novel, reference-free evaluation methodology that reflects how lawyers evaluate legal answers; b) we demonstrate that our method outperforms a variety of baselines on both our proprietary dataset and an open-source dataset (LegalBench); c) we show how our method correlates more closely with human expert evaluations and helps improve inter-annotator agreement; and finally d) we open source our Legal Data Points for a subset of LegalBench used in our experiments, allowing the research community to replicate our results and advance research in this vital area of LLM evaluation on legal question-answering.