Conventional end-to-end (E2E) driving models are effective at generating physically plausible trajectories, but often fail to generalize to long-tail scenarios due to the lack of essential world knowledge to understand and reason about surrounding environments. In contrast, Vision-Language-Action (VLA) models leverage world knowledge to handle challenging cases, but their limited 3D reasoning capability can lead to physically infeasible actions. In this work we introduce DiffVLA++, an enhanced autonomous driving framework that explicitly bridges cognitive reasoning and E2E planning through metric-guided alignment. First, we build a VLA module directly generating semantically grounded driving trajectories. Second, we design an E2E module with a dense trajectory vocabulary that ensures physical feasibility. Third, and most critically, we introduce a metric-guided trajectory scorer that guides and aligns the outputs of the VLA and E2E modules, thereby integrating their complementary strengths. The experiment on the ICCV 2025 Autonomous Grand Challenge leaderboard shows that our model achieves EPDMS of 49.12.

Nanopore sequencing enables real-time long-read DNA sequencing with reads exceeding 10 kilobases, but inherent error rates of 12-15 percent present significant computational challenges for read alignment. The critical seed chaining step must connect exact k-mer matches between reads and reference genomes while filtering spurious matches, yet state-of-the-art methods rely on fixed gap penalty functions unable to adapt to varying genomic contexts including tandem repeats and structural variants. This paper presents RawHash3, a hybrid framework combining graph neural networks with classical dynamic programming for adaptive seed chaining that maintains real-time performance while providing statistical guarantees. We formalize seed chaining as graph learning where seeds constitute nodes with 12-dimensional feature vectors and edges encode 8-dimensional spatial relationships including gap consistency. Our architecture employs three-layer EdgeConv GNN with confidence-based method selection that dynamically switches between learned guidance and algorithmic fallback. Comprehensive evaluation on 1,000 synthetic nanopore reads with 5,200 test seeds demonstrates RawHash3 achieves 99.94 percent precision and 40.07 percent recall, representing statistically significant 25.0 percent relative improvement over baseline with p less than 0.001. The system maintains median inference latency of 1.59ms meeting real-time constraints, while demonstrating superior robustness with 100 percent success rate under 20 percent label corruption versus baseline degradation to 30.3 percent. Cross-validation confirms stability establishing graph neural networks as viable approach for production genomics pipelines.

Parkinson's disease assessment has garnered growing interest in recent years, particularly with the advent of sensor data and machine learning techniques. Among these, multimodal approaches have demonstrated strong performance by effectively integrating complementary information from various data sources. However, two major limitations hinder their practical application: (1) the need to synchronize all modalities during training, and (2) the dependence on all modalities during inference. To address these issues, we propose the first Parkinson's assessment system that formulates multimodal learning as a multi-objective optimization (MOO) problem. This not only allows for more flexible modality requirements during both training and inference, but also handles modality collapse issue during multimodal information fusion. In addition, to mitigate the imbalance within individual modalities, we introduce a margin-based class rebalancing strategy to enhance category learning. We conduct extensive experiments on three public datasets under both synchronous and asynchronous settings. The results show that our framework-Towards Relaxed InPuts (TRIP)-achieves state-of-the-art performance, outperforming the best baselines by 16.48, 6.89, and 11.55 percentage points in the asynchronous setting, and by 4.86 and 2.30 percentage points in the synchronous setting, highlighting its effectiveness and adaptability.

Cascade ranking is a widely adopted paradigm in large-scale information retrieval systems for Top-K item selection. However, the Top-K operator is non-differentiable, hindering end-to-end training. Existing methods include Learning-to-Rank approaches (e.g., LambdaLoss), which optimize ranking metrics like NDCG and suffer from objective misalignment, and differentiable sorting-based methods (e.g., ARF, LCRON), which relax permutation matrices for direct Top-K optimization but introduce gradient conflicts through matrix aggregation. A promising alternative is to directly construct a differentiable approximation of the Top-K selection operator, bypassing the use of soft permutation matrices. However, even state-of-the-art differentiable Top-K operator (e.g., LapSum) require $O(n \log n)$ complexity due to their dependence on sorting for solving the threshold. Thus, we propose DFTopK, a novel differentiable Top-K operator achieving optimal $O(n)$ time complexity. By relaxing normalization constraints, DFTopK admits a closed-form solution and avoids sorting. DFTopK also avoids the gradient conflicts inherent in differentiable sorting-based methods. We evaluate DFTopK on both the public benchmark RecFLow and an industrial system. Experimental results show that DFTopK significantly improves training efficiency while achieving superior performance, which enables us to scale up training samples more efficiently. In the online A/B test, DFTopK yielded a +1.77% revenue lift with the same computational budget compared to the baseline. To the best of our knowledge, this work is the first to introduce differentiable Top-K operators into recommendation systems and the first to achieve theoretically optimal linear-time complexity for Top-K selection. We have open-sourced our implementation to facilitate future research in both academia and industry.

Language models are increasingly applied to biological sequences like proteins and mRNA, yet their default Euclidean geometry may mismatch the hierarchical structures inherent to biological data. While hyperbolic geometry provides a better alternative for accommodating hierarchical data, it has yet to find a way into language modeling for mRNA sequences. In this work, we introduce HyperHELM, a framework that implements masked language model pre-training in hyperbolic space for mRNA sequences. Using a hybrid design with hyperbolic layers atop Euclidean backbone, HyperHELM aligns learned representations with the biological hierarchy defined by the relationship between mRNA and amino acids. Across multiple multi-species datasets, it outperforms Euclidean baselines on 9 out of 10 tasks involving property prediction, with 10% improvement on average, and excels in out-of-distribution generalization to long and low-GC content sequences; for antibody region annotation, it surpasses hierarchy-aware Euclidean models by 3% in annotation accuracy. Our results highlight hyperbolic geometry as an effective inductive bias for hierarchical language modeling of mRNA sequences. Language models have been increasingly applied to biological sequence data, fueled by the growth of large-scale omics datasets (Lin et al., 2023; Celaj et al., 2023; Brixi et al., 2025). The biological sequences, however, are structured differently from natural language, particularly in their hierarchical organization, where nucleotides or amino acids form motifs that can be nested within larger functional groups (Buhr et al., 2016). In this work, we take the rapidly expanding therapeutic domain of RNA, where the codon-amino acid hierarchy plays a key role in determining the biophysical properties of mRNA sequences and their expressed proteins (Clancy & Brown, 2008), and we focus on encoding this hierarchy directly into the representation space of a bio-language model by leveraging hyperbolic geometry.

Deep learning has achieved remarkable success across domains such as vision, language, and science. A widely believed explanation for this success is representation learning -- also called feature learning -- the empirically observed ability of deep models to automatically extract task-relevant features from raw data, without manual engineering, to support downstream prediction [1]. This ability is generally attributed to two fundamental ingredients of deep models: (i) their compositional architecture and (ii) the use of optimization. The compositionality of the architecture endows the model with the ability to form intermediate representations of the data via composition of simple transformations. These representations are not manually defined but are learned from data by optimizing a loss function designed to minimize prediction error. However, despite the empirical success of this paradigm, our theoretical understanding of how and why such representations emerge remains fundamentally limited. In particular, it remains unclear how the interplay between compositional structure and optimization gives rise to task-aligned features -- and under what conditions this mechanism succeeds or fails. To address this gap, we study a stylized compositional model that preserves these two core ingredients of feature learning -- while remaining simple enough to enable analysis of how features are learnt during training.

Major depressive disorder (MDD) is a prevalent mental health condition that negatively impacts both individual well-being and global public health. Automated detection of MDD using structural magnetic resonance imaging (sMRI) and deep learning (DL) methods holds increasing promise for improving diagnostic accuracy and enabling early intervention. Most existing methods employ either voxel-level features or handcrafted regional representations built from predefined brain atlases, limiting their ability to capture complex brain patterns. This paper develops a unified pipeline that utilizes Vision Transformers (ViTs) for extracting 3D region embeddings from sMRI data and Graph Neural Network (GNN) for classification. We explore two strategies for defining regions: (1) an atlas-based approach using predefined structural and functional brain atlases, and (2) an cube-based method by which ViTs are trained directly to identify regions from uniformly extracted 3D patches. Further, cosine similarity graphs are generated to model interregional relationships, and guide GNN-based classification. Extensive experiments were conducted using the REST-meta-MDD dataset to demonstrate the effectiveness of our model. With stratified 10-fold cross-validation, the best model obtained 81.51\% accuracy, 85.94\% sensitivity, 76.36\% specificity, 80.88\% precision, and 83.33\% F1-score. Further, atlas-based models consistently outperformed the cube-based approach, highlighting the importance of using domain-specific anatomical priors for MDD detection.

Structure-based drug design (SBDD), aiming to generate 3D molecules with high binding affinity toward target proteins, is a vital approach in novel drug discovery. Although recent generative models have shown great potential, they suffer from unstable probability dynamics and mismatch between generated molecule size and the protein pockets geometry, resulting in inconsistent quality and off-target effects. We propose PAFlow, a novel target-aware molecular generation model featuring prior interaction guidance and a learnable atom number predictor. PAFlow adopts the efficient flow matching framework to model the generation process and constructs a new form of conditional flow matching for discrete atom types. A protein-ligand interaction predictor is incorporated to guide the vector field toward higher-affinity regions during generation, while an atom number predictor based on protein pocket information is designed to better align generated molecule size with target geometry. Extensive experiments on the CrossDocked2020 benchmark show that PAFlow achieves a new state-of-the-art in binding affinity (up to -8.31 Avg. Vina Score), simultaneously maintains favorable molecular properties.

This paper introduces an algorithm to select demonstration examples for in-context learning of a query set. Given a set of $n$ examples, how can we quickly select $k$ out of $n$ to best serve as the conditioning for downstream inference? This problem has broad applications in prompt tuning and chain-of-thought reasoning. Since model weights remain fixed during in-context learning, previous work has sought to design methods based on the similarity of token embeddings. This work proposes a new approach based on gradients of the output taken in the input embedding space. Our approach estimates model outputs through a first-order approximation using the gradients. Then, we apply this estimation to multiple randomly sampled subsets. Finally, we aggregate the sampled subset outcomes to form an influence score for each demonstration, and select $k$ most relevant examples. This procedure only requires pre-computing model outputs and gradients once, resulting in a linear-time algorithm relative to model and training set sizes. Extensive experiments across various models and datasets validate the efficiency of our approach. We show that the gradient estimation procedure yields approximations of full inference with less than ${1}\%$ error across six datasets. This allows us to scale up subset selection that would otherwise run full inference by up to ${37.7}\times$ on models with up to $34$ billion parameters, and outperform existing selection methods based on input embeddings by ${11}\%$ on average.

Safe deployment of machine learning (ML) models in safety-critical domains such as medical imaging requires detecting inputs with characteristics not seen during training, known as out-of-distribution (OOD) detection, to prevent unreliable predictions. Effective OOD detection after deployment could benefit from access to the training data, enabling direct comparison between test samples and the training data distribution to identify differences. State-of-the-art OOD detection methods, however, either discard the training data after deployment or assume that test samples and training data are centrally stored together, an assumption that rarely holds in real-world settings. This is because shipping the training data with the deployed model is usually impossible due to the size of training databases, as well as proprietary or privacy constraints. We introduce the Isolation Network, an OOD detection framework that quantifies the difficulty of separating a target test sample from the training data by solving a binary classification task. We then propose Decentralized Isolation Networks (DIsoN), which enables the comparison of training and test data when data-sharing is impossible, by exchanging only model parameters between the remote computational nodes of training and deployment. We further extend DIsoN with class-conditioning, comparing a target sample solely with training data of its predicted class. We evaluate DIsoN on four medical imaging datasets (dermatology, chest X-ray, breast ultrasound, histopathology) across 12 OOD detection tasks. DIsoN performs favorably against existing methods while respecting data-privacy. This decentralized OOD detection framework opens the way for a new type of service that ML developers could provide along with their models: providing remote, secure utilization of their training data for OOD detection services. Code: https://github.com/FelixWag/DIsoN