Graph-based Retrieval-Augmented Generation (Graph-RAG) enhances large language models (LLMs) by structuring retrieval over an external corpus. However, existing approaches typically assume a static corpus, requiring expensive full-graph reconstruction whenever new documents arrive, limiting their scalability in dynamic, evolving environments. To address these limitations, we introduce EraRAG, a novel multi-layered Graph-RAG framework that supports efficient and scalable dynamic updates. Our method leverages hyperplane-based Locality-Sensitive Hashing (LSH) to partition and organize the original corpus into hierarchical graph structures, enabling efficient and localized insertions of new data without disrupting the existing topology. The design eliminates the need for retraining or costly recomputation while preserving high retrieval accuracy and low latency. Experiments on large-scale benchmarks demonstrate that EraRag achieves up to an order of magnitude reduction in update time and token consumption compared to existing Graph-RAG systems, while providing superior accuracy performance. This work offers a practical path forward for RAG systems that must operate over continually growing corpora, bridging the gap between retrieval efficiency and adaptability. Our code and data are available at https://github.com/EverM0re/EraRAG-Official.
This paper introduces an active learning framework for manifold Gaussian Process (GP) regression, combining manifold learning with strategic data selection to improve accuracy in high-dimensional spaces. Our method jointly optimizes a neural network for dimensionality reduction and a Gaussian process regressor in the latent space, supervised by an active learning criterion that minimizes global prediction error. Experiments on synthetic data demonstrate superior performance over randomly sequential learning. The framework efficiently handles complex, discontinuous functions while preserving computational tractability, offering practical value for scientific and engineering applications. Future work will focus on scalability and uncertainty-aware manifold learning.
We develop a cost-efficient neurosymbolic agent to address challenging multi-turn image editing tasks such as "Detect the bench in the image while recoloring it to pink. Also, remove the cat for a clearer view and recolor the wall to yellow.'' It combines the fast, high-level subtask planning by large language models (LLMs) with the slow, accurate, tool-use, and local A$^*$ search per subtask to find a cost-efficient toolpath -- a sequence of calls to AI tools. To save the cost of A$^*$ on similar subtasks, we perform inductive reasoning on previously successful toolpaths via LLMs to continuously extract/refine frequently used subroutines and reuse them as new tools for future tasks in an adaptive fast-slow planning, where the higher-level subroutines are explored first, and only when they fail, the low-level A$^*$ search is activated. The reusable symbolic subroutines considerably save exploration cost on the same types of subtasks applied to similar images, yielding a human-like fast-slow toolpath agent "FaSTA$^*$'': fast subtask planning followed by rule-based subroutine selection per subtask is attempted by LLMs at first, which is expected to cover most tasks, while slow A$^*$ search is only triggered for novel and challenging subtasks. By comparing with recent image editing approaches, we demonstrate FaSTA$^*$ is significantly more computationally efficient while remaining competitive with the state-of-the-art baseline in terms of success rate.
Contrastive learning (CL) has become a cornerstone of self-supervised pretraining (SSP) in foundation models, however, extending CL to pixel-wise representation, crucial for medical vision, remains an open problem. Standard CL formulates SSP as a binary optimization problem (binary CL) where the excessive pursuit of feature dispersion leads to an over-dispersion problem, breaking pixel-wise feature correlation thus disrupting the intra-class distribution. Our vector CL reformulates CL as a vector regression problem, enabling dispersion quantification in pixel-wise pretraining via modeling feature distances in regressing displacement vectors. To implement this novel paradigm, we propose the COntrast in VEctor Regression (COVER) framework. COVER establishes an extendable vector-based self-learning, enforces a consistent optimization flow from vector regression to distance modeling, and leverages a vector pyramid architecture for granularity adaptation, thus preserving pixel-wise feature correlations in SSP. Extensive experiments across 8 tasks, spanning 2 dimensions and 4 modalities, show that COVER significantly improves pixel-wise SSP, advancing generalizable medical visual foundation models.
Survival prediction using whole slide images (WSIs) can be formulated as a multiple instance learning (MIL) problem. However, existing MIL methods often fail to explicitly capture pathological heterogeneity within WSIs, both globally -- through long-tailed morphological distributions, and locally through -- tile-level prediction uncertainty. Optimal transport (OT) provides a principled way of modeling such heterogeneity by incorporating marginal distribution constraints. Building on this insight, we propose OTSurv, a novel MIL framework from an optimal transport perspective. Specifically, OTSurv formulates survival predictions as a heterogeneity-aware OT problem with two constraints: (1) global long-tail constraint that models prior morphological distributions to avert both mode collapse and excessive uniformity by regulating transport mass allocation, and (2) local uncertainty-aware constraint that prioritizes high-confidence patches while suppressing noise by progressively raising the total transport mass. We then recast the initial OT problem, augmented by these constraints, into an unbalanced OT formulation that can be solved with an efficient, hardware-friendly matrix scaling algorithm. Empirically, OTSurv sets new state-of-the-art results across six popular benchmarks, achieving an absolute 3.6% improvement in average C-index. In addition, OTSurv achieves statistical significance in log-rank tests and offers high interpretability, making it a powerful tool for survival prediction in digital pathology. Our codes are available at https://github.com/Y-Research-SBU/OTSurv.
Information retrieval is a cornerstone of modern knowledge acquisition, enabling billions of queries each day across diverse domains. However, traditional keyword-based search engines are increasingly inadequate for handling complex, multi-step information needs. Our position is that Large Language Models (LLMs), endowed with reasoning and agentic capabilities, are ushering in a new paradigm termed Agentic Deep Research. These systems transcend conventional information search techniques by tightly integrating autonomous reasoning, iterative retrieval, and information synthesis into a dynamic feedback loop. We trace the evolution from static web search to interactive, agent-based systems that plan, explore, and learn. We also introduce a test-time scaling law to formalize the impact of computational depth on reasoning and search. Supported by benchmark results and the rise of open-source implementations, we demonstrate that Agentic Deep Research not only significantly outperforms existing approaches, but is also poised to become the dominant paradigm for future information seeking. All the related resources, including industry products, research papers, benchmark datasets, and open-source implementations, are collected for the community in https://github.com/DavidZWZ/Awesome-Deep-Research.
We introduce GRASP, a simple Bayesian framework for regression with grouped predictors, built on the normal beta prime (NBP) prior. The NBP prior is an adaptive generalization of the horseshoe prior with tunable hyperparameters that control tail behavior, enabling a flexible range of sparsity, from strong shrinkage to ridge-like regularization. Unlike prior work that introduced the group inverse-gamma gamma (GIGG) prior by decomposing the NBP prior into structured hierarchies, we show that directly controlling the tails is sufficient without requiring complex hierarchical constructions. Extending the non-tail adaptive grouped half-Cauchy hierarchy of Xu et al., GRASP assigns the NBP prior to both local and group shrinkage parameters allowing adaptive sparsity within and across groups. A key contribution of this work is a novel framework to explicitly quantify correlations among shrinkage parameters within a group, providing deeper insights into grouped shrinkage behavior. We also introduce an efficient Metropolis-Hastings sampler for hyperparameter estimation. Empirical results on simulated and real-world data demonstrate the robustness and versatility of GRASP across grouped regression problems with varying sparsity and signal-to-noise ratios.
Assessing the quality of LLM-generated text remains a fundamental challenge in natural language processing. Current evaluation approaches often rely on isolated metrics or simplistic aggregations that fail to capture the nuanced trade-offs between coherence, diversity, fluency, and other relevant indicators of text quality. In this work, we adapt a recently proposed framework for statistical inference based on Generalized Stochastic Dominance (GSD) that addresses three critical limitations in existing benchmarking methodologies: the inadequacy of single-metric evaluation, the incompatibility between cardinal automatic metrics and ordinal human judgments, and the lack of inferential statistical guarantees. The GSD-front approach enables simultaneous evaluation across multiple quality dimensions while respecting their different measurement scales, building upon partial orders of decoding strategies, thus avoiding arbitrary weighting of the involved metrics. By applying this framework to evaluate common decoding strategies against human-generated text, we demonstrate its ability to identify statistically significant performance differences while accounting for potential deviations from the i.i.d. assumption of the sampling design.
Vision-Language Models (VLMs) have rapidly advanced alongside Large Language Models (LLMs). This study evaluates the capabilities of prominent generative VLMs, such as GPT-4.1 and Gemini 2.5 Pro, accessed via APIs, for histopathology image classification tasks, including cell typing. Using diverse datasets from public and private sources, we apply zero-shot and one-shot prompting methods to assess VLM performance, comparing them against custom-trained Convolutional Neural Networks (CNNs). Our findings demonstrate that while one-shot prompting significantly improves VLM performance over zero-shot ($p \approx 1.005 \times 10^{-5}$ based on Kappa scores), these general-purpose VLMs currently underperform supervised CNNs on most tasks. This work underscores both the promise and limitations of applying current VLMs to specialized domains like pathology via in-context learning. All code and instructions for reproducing the study can be accessed from the repository https://www.github.com/a12dongithub/VLMCCE.
We propose a profitable trading strategy for the cryptocurrency market based on grid trading. Starting with an analysis of the expected value of the traditional grid strategy, we show that under simple assumptions, its expected return is essentially zero. We then introduce a novel Dynamic Grid-based Trading (DGT) strategy that adapts to market conditions by dynamically resetting grid positions. Our backtesting results using minute-level data from Bitcoin and Ethereum between January 2021 and July 2024 demonstrate that the DGT strategy significantly outperforms both the traditional grid and buy-and-hold strategies in terms of internal rate of return and risk control.
Causal inference in longitudinal biomedical data remains a central challenge, especially in psychiatry, where symptom heterogeneity and latent confounding frequently undermine classical estimators. Most existing methods for treatment effect estimation presuppose a fixed outcome variable and address confounding through observed covariate adjustment. However, the assumption of unconfoundedness may not hold for a fixed outcome in practice. To address this foundational limitation, we directly optimize the outcome definition to maximize causal identifiability. Our DEBIAS (Durable Effects with Backdoor-Invariant Aggregated Symptoms) algorithm learns non-negative, clinically interpretable weights for outcome aggregation, maximizing durable treatment effects and empirically minimizing both observed and latent confounding by leveraging the time-limited direct effects of prior treatments in psychiatric longitudinal data. The algorithm also furnishes an empirically verifiable test for outcome unconfoundedness. DEBIAS consistently outperforms state-of-the-art methods in recovering causal effects for clinically interpretable composite outcomes across comprehensive experiments in depression and schizophrenia.
Virtual brain twins are personalized digital models of individual human subject or patient's brains, allowing for mechanistic interpretation of neuroimaging data features. Training and inference with these models however presents a pair of challenges: large shared infrastructure do not allow for use of personal data and inference in clinical applications should not require significant resources. We introduce "anonymized personalization" to address both by expanding model priors to include personalization which under amortized inference allows training to be performed anonymously, while inference is both personalized and lightweight. We illustrate the basic approach, demonstrate reliability in an example, and discuss the impact on both experimental and computational neuroscience. Code is available at https://github.com/ins-amu/apvbt.
The accurate development, assessment, interpretation, and benchmarking of bioinformatics frameworks for analyzing transcriptional regulatory grammars rely on controlled simulations to validate the underlying methods. However, existing simulators often lack end-to-end flexibility or ease of integration, which limits their practical use. We present inMOTIFin, a lightweight, modular, and user-friendly Python-based software that addresses these gaps by providing versatile and efficient simulation and modification of DNA regulatory sequences. inMOTIFin enables users to simulate or modify regulatory sequences efficiently for the customizable generation of motifs and insertion of motif instances with precise control over their positions, co-occurrences, and spacing, as well as direct modification of real sequences, facilitating a comprehensive evaluation of motif-based methods and interpretation tools. We demonstrate inMOTIFin applications for the assessment of de novo motif discovery prediction, the analysis of transcription factor cooperativity, and the support of explainability analyses for deep learning models. inMOTIFin ensures robust and reproducible analyses for studying transcriptional regulatory grammars. inMOTIFin is available at PyPI https://pypi.org/project/inMOTIFin/ and Docker Hub https://hub.docker.com/r/cbgr/inmotifin. Detailed documentation is available at https://inmotifin.readthedocs.io/en/latest/. The code for use case analyses is available at https://bitbucket.org/CBGR/inmotifin_evaluation/src/main/.
Human languages differ widely in their forms, each having distinct sounds, scripts, and syntax. Yet, they can all convey similar meaning. Do different languages converge on a shared neural substrate for conceptual meaning? We used language models (LMs) and naturalistic fMRI to identify neural representations of the shared conceptual meaning of the same story as heard by native speakers of three languages: English, Chinese, and French. We found that LMs trained on entirely different languages converge onto a similar embedding space, especially in the middle layers. We then aimed to find if a similar shared space exists in the brains of different native speakers of the three languages. We trained voxelwise encoding models that align the LM embeddings with neural responses from one group of subjects speaking a single language. We then used the encoding models trained on one language to predict the neural activity in listeners of other languages. We found that models trained to predict neural activity for one language generalize to different subjects listening to the same content in a different language, across high-level language and default-mode regions. Our results suggest that the neural representations of meaning underlying different languages are shared across speakers of various languages, and that LMs trained on different languages converge on this shared meaning. These findings suggest that, despite the diversity of languages, shared meaning emerges from our interactions with one another and our shared world.
To understand how genetic variants in human genomes manifest in phenotypes -- traits like height or diseases like asthma -- geneticists have sequenced and measured hundreds of thousands of individuals. Geneticists use this data to build models that predict how a genetic variant impacts phenotype given genomic features of the variant, like DNA accessibility or the presence of nearby DNA-bound proteins. As more data and features become available, one might expect predictive models to improve. Unfortunately, training these models is bottlenecked by the need to solve expensive linear algebra problems because variants in the genome are correlated with nearby variants, requiring inversion of large matrices. Previous methods have therefore been restricted to fitting small models, and fitting simplified summary statistics, rather than the full likelihood of the statistical model. In this paper, we leverage modern fast linear algebra techniques to develop DeepWAS (Deep genome Wide Association Studies), a method to train large and flexible neural network predictive models to optimize likelihood. Notably, we find that larger models only improve performance when using our full likelihood approach; when trained by fitting traditional summary statistics, larger models perform no better than small ones. We find larger models trained on more features make better predictions, potentially improving disease predictions and therapeutic target identification.
Riemannian representation learning typically relies on approximating densities on chosen manifolds. This involves optimizing difficult objectives, potentially harming models. To completely circumvent this issue, we introduce the Riemannian generative decoder which finds manifold-valued maximum likelihood latents with a Riemannian optimizer while training a decoder network. By discarding the encoder, we vastly simplify the manifold constraint compared to current approaches which often only handle few specific manifolds. We validate our approach on three case studies -- a synthetic branching diffusion process, human migrations inferred from mitochondrial DNA, and cells undergoing a cell division cycle -- each showing that learned representations respect the prescribed geometry and capture intrinsic non-Euclidean structure. Our method requires only a decoder, is compatible with existing architectures, and yields interpretable latent spaces aligned with data geometry.
Extrachromosomal circular DNA (eccDNA) plays key regulatory roles and contributes to oncogene overexpression in cancer through high-copy amplification and long-range interactions. Despite advances in modeling, no pre-trained models currently support full-length circular eccDNA for downstream analysis. Existing genomic models are either limited to single-nucleotide resolution or hindered by the inefficiency of the quadratic attention mechanism. Here, we introduce eccDNAMamba, the first bidirectional state-space encoder tailored for circular DNA sequences. It combines forward and reverse passes for full-context representation learning with linear-time complexity, and preserves circular structure through a novel augmentation strategy. Tested on two real-world datasets, eccDNAMamba achieves strong classification performance and scales to sequences up to 200 Kbp, offering a robust and efficient framework for modeling circular genomes. Our codes are available at https://github.com/zzq1zh/GenAI-Lab.
Traditional artificial neural networks consist of nodes with non-oscillatory dynamics. Biological neural networks, on the other hand, consist of oscillatory components embedded in an oscillatory environment. Motivated by this feature of biological neurons, we describe a reservoir computing framework with explicit damped, oscillatory node dynamics. We express the oscillatory dynamics using two history dependent terms to connect these dynamics with existing artificial neural network approaches and apply physical and stationary constraints to reduce the number of free parameters. We then optimize and illustrate reservoir performance by classifying different brain rhythms associated with epilepsy and show that reservoir elements support classification by resonating with features of the input signals. Applying the same reservoir network to visual and auditory signal types, we show the reservoir generalizes for accurate classification with few trainable parameters. Compared to existing artificial neural network approaches, the proposed resonant reservoir network (RRN) utilizes oscillatory dynamics expressed as a straightforward extension of traditional artificial neural networks, produces interpretable features for classification, avoids computationally expensive training (e.g., backpropagation), and performs well with few parameters in different classification scenarios. We propose that RRNs may serve as efficient, biologically implemented building blocks to achieve complex goals in biological and artificial neural networks.
Reconstructing the attractors of complex nonlinear dynamical systems from available measurements is key to analyse and predict their time evolution. Existing attractor reconstruction methods typically rely on topological embedding and may produce poor reconstructions, which differ significantly from the actual attractor, because measurements are corrupted by noise and often available only for some of the state variables and/or their combinations, and the time series are often relatively short. Here, we propose the use of Homogeneous Differentiators (HD) to effectively de-noise measurements and more faithfully reconstruct attractors of nonlinear systems. Homogeneous Differentiators are supported by rigorous theoretical guarantees about their de-noising capabilities, and their results can be fruitfully combined with time-delay embedding, differential embedding and functional observability. We apply our proposed HD-based methodology to simulated dynamical models of increasing complexity, from the Lorenz system to the Hindmarsh-Rose model and the Epileptor model for neural dynamics, as well as to empirical data of EEG recordings. In the presence of corrupting noise of various types, we obtain drastically improved quality and resolution of the reconstructed attractors, as well as significantly reduced computational time, which can be orders of magnitude lower than that of alternative methods. Our tests show the flexibility and effectiveness of Homogeneous Differentiators and suggest that they can become the tool of choice for preprocessing noisy signals and reconstructing attractors of highly nonlinear dynamical systems from both theoretical models and real data.
Optimal transport provides a robust framework for comparing probability distributions. Its effectiveness is significantly influenced by the choice of the underlying ground metric. Traditionally, the ground metric has either been (i) predefined, e.g., as the Euclidean distance, or (ii) learned in a supervised way, by utilizing labeled data to learn a suitable ground metric for enhanced task-specific performance. Yet, predefined metrics typically cannot account for the inherent structure and varying importance of different features in the data, and existing supervised approaches to ground metric learning often do not generalize across multiple classes or are restricted to distributions with shared supports. To address these limitations, we propose a novel approach for learning metrics for arbitrary distributions over a shared metric space. Our method provides a distance between individual points like a global metric, but requires only class labels on a distribution-level for training. The learned global ground metric enables more accurate optimal transport distances, leading to improved performance in embedding, clustering and classification tasks. We demonstrate the effectiveness and interpretability of our approach using patient-level scRNA-seq data spanning multiple diseases.