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Apr 17

Revisiting the Shape Convention of Transformer Language Models

Dense Transformer language models have largely adhered to one consistent architectural shape: each layer consists of an attention module followed by a feed-forward network (FFN) with a narrow-wide-narrow MLP, allocating most parameters to the MLP at expansion ratios between 2 and 4. Motivated by recent results that residual wide-narrow-wide (hourglass) MLPs offer superior function approximation capabilities, we revisit the long-standing MLP shape convention in Transformer, challenging the necessity of the narrow-wide-narrow design. To study this, we develop a Transformer variant that replaces the conventional FFN with a deeper hourglass-shaped FFN, comprising a stack of hourglass sub-MLPs connected by residual pathways. We posit that a deeper but lighter hourglass FFN can serve as a competitive alternative to the conventional FFN, and that parameters saved by using a lighter hourglass FFN can be more effectively utilized, such as by enlarging model hidden dimensions under fixed budgets. We confirm these through empirical validations across model scales: hourglass FFNs outperform conventional FFNs up to 400M and achieve comparable performance at larger scales to 1B parameters; hourglass FFN variants with reduced FFN and increased attention parameters show consistent improvements over conventional configurations at matched budgets. Together, these findings shed new light on recent work and prompt a rethinking of the narrow-wide-narrow MLP convention and the balance between attention and FFN towards efficient and expressive modern language models.

MediaTek-Research MediaTek Research
ยท
Feb 6 2

Residual Stream Duality in Modern Transformer Architectures

Recent work has made clear that the residual pathway is not mere optimization plumbing; it is part of the model's representational machinery. We agree, but argue that the cleanest way to organize this design space is through a two-axis view of the Transformer. A decoder evolves information along two ordered dimensions: sequence position and layer depth. Self-attention already provides adaptive mixing along the sequence axis, whereas the residual stream usually performs fixed addition along the depth axis. If we fix a token position and treat layer index as the ordered variable, then a causal depth-wise residual attention read is exactly the same local operator as causal short sliding-window attention (ShortSWA), except written over depth rather than over sequence. This is the core residual stream duality behind Transformer^2. This perspective also clarifies the recent literature. ELC-BERT and DenseFormer already show that learned aggregation over depth can outperform uniform residual accumulation, while Vertical Attention, DeepCrossAttention (DCA), MUDDFormer, and Attention Residuals move further toward explicit attention-based routing over earlier layers. The key point, however, is that operator-level duality does not imply systems-level symmetry. For large-scale autoregressive models, sequence-axis ShortSWA is usually the more hardware-friendly placement because it reuses token-side sliding-window kernels, KV-cache layouts, and chunked execution. If the goal is instead to change the shortcut itself, Deep Delta Learning (DDL) is the cleaner intervention because it modifies the residual operator directly rather than adding a separate cross-layer retrieval path. Our recommendation is therefore simple: use DDL when the shortcut is the object of interest, and use sequence-axis ShortSWA when the goal is local adaptive mixing.

math-ai math-ai
ยท
Mar 16 2

Surprised by Attention: Predictable Query Dynamics for Time Series Anomaly Detection

Multivariate time series anomalies often manifest as shifts in cross-channel dependencies rather than simple amplitude excursions. In autonomous driving, for instance, a steering command might be internally consistent but decouple from the resulting lateral acceleration. Residual-based detectors can miss such anomalies when flexible sequence models still reconstruct signals plausibly despite altered coordination. We introduce AxonAD, an unsupervised detector that treats multi-head attention query evolution as a short horizon predictable process. A gradient-updated reconstruction pathway is coupled with a history-only predictor that forecasts future query vectors from past context. This is trained via a masked predictor-target objective against an exponential moving average (EMA) target encoder. At inference, reconstruction error is combined with a tail-aggregated query mismatch score, which measures cosine deviation between predicted and target queries on recent timesteps. This dual approach provides sensitivity to structural dependency shifts while retaining amplitude-level detection. On proprietary in-vehicle telemetry with interval annotations and on the TSB-AD multi-variate suite (17 datasets, 180 series) with threshold-free and range-aware metrics, AxonAD improves ranking quality and temporal localization over strong baselines. Ablations confirm that query prediction and combined scoring are the primary drivers of the observed gains. Code is available at the URL https://github.com/iis-esslingen/AxonAD.

Mercedes-Benz Mercedes-Benz AG
ยท
Mar 13 2

I-GLIDE: Input Groups for Latent Health Indicators in Degradation Estimation

Accurate remaining useful life (RUL) prediction hinges on the quality of health indicators (HIs), yet existing methods often fail to disentangle complex degradation mechanisms in multi-sensor systems or quantify uncertainty in HI reliability. This paper introduces a novel framework for HI construction, advancing three key contributions. First, we adapt Reconstruction along Projected Pathways (RaPP) as a health indicator (HI) for RUL prediction for the first time, showing that it outperforms traditional reconstruction error metrics. Second, we show that augmenting RaPP-derived HIs with aleatoric and epistemic uncertainty quantification (UQ) via Monte Carlo dropout and probabilistic latent spaces- significantly improves RUL-prediction robustness. Third, and most critically, we propose indicator groups, a paradigm that isolates sensor subsets to model system-specific degradations, giving rise to our novel method, I-GLIDE which enables interpretable, mechanism-specific diagnostics. Evaluated on data sourced from aerospace and manufacturing systems, our approach achieves marked improvements in accuracy and generalizability compared to state-of-the-art HI methods while providing actionable insights into system failure pathways. This work bridges the gap between anomaly detection and prognostics, offering a principled framework for uncertainty-aware degradation modeling in complex systems.

orailix Orailix
ยท
Nov 26, 2025 2

Revisiting Data Challenges of Computational Pathology: A Pack-based Multiple Instance Learning Framework

Computational pathology (CPath) digitizes pathology slides into whole slide images (WSIs), enabling analysis for critical healthcare tasks such as cancer diagnosis and prognosis. However, WSIs possess extremely long sequence lengths (up to 200K), significant length variations (from 200 to 200K), and limited supervision. These extreme variations in sequence length lead to high data heterogeneity and redundancy. Conventional methods often compromise on training efficiency and optimization to preserve such heterogeneity under limited supervision. To comprehensively address these challenges, we propose a pack-based MIL framework. It packs multiple sampled, variable-length feature sequences into fixed-length ones, enabling batched training while preserving data heterogeneity. Moreover, we introduce a residual branch that composes discarded features from multiple slides into a hyperslide which is trained with tailored labels. It offers multi-slide supervision while mitigating feature loss from sampling. Meanwhile, an attention-driven downsampler is introduced to compress features in both branches to reduce redundancy. By alleviating these challenges, our approach achieves an accuracy improvement of up to 8% while using only 12% of the training time in the PANDA(UNI). Extensive experiments demonstrate that focusing data challenges in CPath holds significant potential in the era of foundation models. The code is https://github.com/FangHeng/PackMIL

  • 5 authors
ยท
Sep 25, 2025

Residual Denoising Diffusion Models

Current diffusion-based image restoration methods feed degraded input images as conditions into the noise estimation network. However, interpreting this diffusion process is challenging since it essentially generates the target image from the noise. To establish a unified and more interpretable model for image generation and restoration, we propose residual denoising diffusion models (RDDM). In contrast to existing diffusion models (e.g., DDPM or DDIM) that focus solely on noise estimation, our RDDM predicts residuals to represent directional diffusion from the target domain to the input domain, while concurrently estimating noise to account for random perturbations in the diffusion process. The introduction of residuals allows us to redefine the forward diffusion process, wherein the target image progressively diffuses into a purely noisy image or a noise-carrying input image, thus unifying image generation and restoration. We demonstrate that our sampling process is consistent with that of DDPM and DDIM through coefficient transformation, and propose a partially path-independent generation process to better understand the reverse process. Notably, with native support for conditional inputs, our RDDM enables a generic UNet, trained with only an ell _1 loss and a batch size of 1, to compete with state-of-the-art image restoration methods. We provide code and pre-trained models to encourage further exploration, application, and development of our innovative framework (https://github.com/nachifur/RDDM).

  • 6 authors
ยท
Aug 25, 2023

PathReasoner-R1: Instilling Structured Reasoning into Pathology Vision-Language Model via Knowledge-Guided Policy Optimization

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

  • 5 authors
ยท
Jan 29

Rethinking Molecule Synthesizability with Chain-of-Reaction

A well-known pitfall of molecular generative models is that they are not guaranteed to generate synthesizable molecules. There have been considerable attempts to address this problem, but given the exponentially large combinatorial space of synthesizable molecules, existing methods have shown limited coverage of the space and poor molecular optimization performance. To tackle these problems, we introduce ReaSyn, a generative framework for synthesizable projection where the model explores the neighborhood of given molecules in the synthesizable space by generating pathways that result in synthesizable analogs. To fully utilize the chemical knowledge contained in the synthetic pathways, we propose a novel perspective that views synthetic pathways akin to reasoning paths in large language models (LLMs). Specifically, inspired by chain-of-thought (CoT) reasoning in LLMs, we introduce the chain-of-reaction (CoR) notation that explicitly states reactants, reaction types, and intermediate products for each step in a pathway. With the CoR notation, ReaSyn can get dense supervision in every reaction step to explicitly learn chemical reaction rules during supervised training and perform step-by-step reasoning. In addition, to further enhance the reasoning capability of ReaSyn, we propose reinforcement learning (RL)-based finetuning and goal-directed test-time compute scaling tailored for synthesizable projection. ReaSyn achieves the highest reconstruction rate and pathway diversity in synthesizable molecule reconstruction and the highest optimization performance in synthesizable goal-directed molecular optimization, and significantly outperforms previous synthesizable projection methods in synthesizable hit expansion. These results highlight ReaSyn's superior ability to navigate combinatorially-large synthesizable chemical space.

  • 8 authors
ยท
Sep 19, 2025

From Imitation to Refinement -- Residual RL for Precise Visual Assembly

Behavior cloning (BC) currently stands as a dominant paradigm for learning real-world visual manipulation. However, in tasks that require locally corrective behaviors like multi-part assembly, learning robust policies purely from human demonstrations remains challenging. Reinforcement learning (RL) can mitigate these limitations by allowing policies to acquire locally corrective behaviors through task reward supervision and exploration. This paper explores the use of RL fine-tuning to improve upon BC-trained policies in precise manipulation tasks. We analyze and overcome technical challenges associated with using RL to directly train policy networks that incorporate modern architectural components like diffusion models and action chunking. We propose training residual policies on top of frozen BC-trained diffusion models using standard policy gradient methods and sparse rewards, an approach we call ResiP (Residual for Precise manipulation). Our experimental results demonstrate that this residual learning framework can significantly improve success rates beyond the base BC-trained models in high-precision assembly tasks by learning corrective actions. We also show that by combining ResiP with teacher-student distillation and visual domain randomization, our method can enable learning real-world policies for robotic assembly directly from RGB images. Find videos and code at https://residual-assembly.github.io.

  • 5 authors
ยท
Jul 23, 2024

Recurrent Residual Convolutional Neural Network based on U-Net (R2U-Net) for Medical Image Segmentation

Deep learning (DL) based semantic segmentation methods have been providing state-of-the-art performance in the last few years. More specifically, these techniques have been successfully applied to medical image classification, segmentation, and detection tasks. One deep learning technique, U-Net, has become one of the most popular for these applications. In this paper, we propose a Recurrent Convolutional Neural Network (RCNN) based on U-Net as well as a Recurrent Residual Convolutional Neural Network (RRCNN) based on U-Net models, which are named RU-Net and R2U-Net respectively. The proposed models utilize the power of U-Net, Residual Network, as well as RCNN. There are several advantages of these proposed architectures for segmentation tasks. First, a residual unit helps when training deep architecture. Second, feature accumulation with recurrent residual convolutional layers ensures better feature representation for segmentation tasks. Third, it allows us to design better U-Net architecture with same number of network parameters with better performance for medical image segmentation. The proposed models are tested on three benchmark datasets such as blood vessel segmentation in retina images, skin cancer segmentation, and lung lesion segmentation. The experimental results show superior performance on segmentation tasks compared to equivalent models including U-Net and residual U-Net (ResU-Net).

  • 5 authors
ยท
Feb 19, 2018

Retrosynthetic Planning with Dual Value Networks

Retrosynthesis, which aims to find a route to synthesize a target molecule from commercially available starting materials, is a critical task in drug discovery and materials design. Recently, the combination of ML-based single-step reaction predictors with multi-step planners has led to promising results. However, the single-step predictors are mostly trained offline to optimize the single-step accuracy, without considering complete routes. Here, we leverage reinforcement learning (RL) to improve the single-step predictor, by using a tree-shaped MDP to optimize complete routes. Specifically, we propose a novel online training algorithm, called Planning with Dual Value Networks (PDVN), which alternates between the planning phase and updating phase. In PDVN, we construct two separate value networks to predict the synthesizability and cost of molecules, respectively. To maintain the single-step accuracy, we design a two-branch network structure for the single-step predictor. On the widely-used USPTO dataset, our PDVN algorithm improves the search success rate of existing multi-step planners (e.g., increasing the success rate from 85.79% to 98.95% for Retro*, and reducing the number of model calls by half while solving 99.47% molecules for RetroGraph). Additionally, PDVN helps find shorter synthesis routes (e.g., reducing the average route length from 5.76 to 4.83 for Retro*, and from 5.63 to 4.78 for RetroGraph).

  • 10 authors
ยท
Jan 31, 2023

On residual network depth

Deep residual architectures, such as ResNet and the Transformer, have enabled models of unprecedented depth, yet a formal understanding of why depth is so effective remains an open question. A popular intuition, following Veit et al. (2016), is that these residual networks behave like ensembles of many shallower models. Our key finding is an explicit analytical formula that verifies this ensemble perspective, proving that increasing network depth is mathematically equivalent to expanding the size of this implicit ensemble. Furthermore, our expansion reveals a hierarchical ensemble structure in which the combinatorial growth of computation paths leads to an explosion in the output signal, explaining the historical necessity of normalization layers in training deep models. This insight offers a first principles explanation for the historical dependence on normalization layers and sheds new light on a family of successful normalization-free techniques like SkipInit and Fixup. However, while these previous approaches infer scaling factors through optimizer analysis or a heuristic analogy to Batch Normalization, our work offers the first explanation derived directly from the network's inherent functional structure. Specifically, our Residual Expansion Theorem reveals that scaling each residual module provides a principled solution to taming the combinatorial explosion inherent to these architectures. We further show that this scaling acts as a capacity controls that also implicitly regularizes the model's complexity.

  • 2 authors
ยท
Oct 3, 2025

Leveraging Large Language Models as Knowledge-Driven Agents for Reliable Retrosynthesis Planning

Identifying reliable synthesis pathways in materials chemistry is a complex task, particularly in polymer science, due to the intricate and often non-unique nomenclature of macromolecules. To address this challenge, we propose an agent system that integrates large language models (LLMs) and knowledge graphs (KGs). By leveraging LLMs' powerful capabilities for extracting and recognizing chemical substance names, and storing the extracted data in a structured knowledge graph, our system fully automates the retrieval of relevant literatures, extraction of reaction data, database querying, construction of retrosynthetic pathway trees, further expansion through the retrieval of additional literature and recommendation of optimal reaction pathways. A novel Multi-branched Reaction Pathway Search (MBRPS) algorithm enables the exploration of all pathways, with a particular focus on multi-branched ones, helping LLMs overcome weak reasoning in multi-branched paths. This work represents the first attempt to develop a fully automated retrosynthesis planning agent tailored specially for macromolecules powered by LLMs. Applied to polyimide synthesis, our new approach constructs a retrosynthetic pathway tree with hundreds of pathways and recommends optimized routes, including both known and novel pathways, demonstrating its effectiveness and potential for broader applications.

  • 3 authors
ยท
Jan 15, 2025

Residual Off-Policy RL for Finetuning Behavior Cloning Policies

Recent advances in behavior cloning (BC) have enabled impressive visuomotor control policies. However, these approaches are limited by the quality of human demonstrations, the manual effort required for data collection, and the diminishing returns from increasing offline data. In comparison, reinforcement learning (RL) trains an agent through autonomous interaction with the environment and has shown remarkable success in various domains. Still, training RL policies directly on real-world robots remains challenging due to sample inefficiency, safety concerns, and the difficulty of learning from sparse rewards for long-horizon tasks, especially for high-degree-of-freedom (DoF) systems. We present a recipe that combines the benefits of BC and RL through a residual learning framework. Our approach leverages BC policies as black-box bases and learns lightweight per-step residual corrections via sample-efficient off-policy RL. We demonstrate that our method requires only sparse binary reward signals and can effectively improve manipulation policies on high-degree-of-freedom (DoF) systems in both simulation and the real world. In particular, we demonstrate, to the best of our knowledge, the first successful real-world RL training on a humanoid robot with dexterous hands. Our results demonstrate state-of-the-art performance in various vision-based tasks, pointing towards a practical pathway for deploying RL in the real world. Project website: https://residual-offpolicy-rl.github.io

  • 6 authors
ยท
Sep 23, 2025 2

Attention Residuals

Residual connections with PreNorm are standard in modern LLMs, yet they accumulate all layer outputs with fixed unit weights. This uniform aggregation causes uncontrolled hidden-state growth with depth, progressively diluting each layer's contribution. We propose Attention Residuals (AttnRes), which replaces this fixed accumulation with softmax attention over preceding layer outputs, allowing each layer to selectively aggregate earlier representations with learned, input-dependent weights. To address the memory and communication overhead of attending over all preceding layer outputs for large-scale model training, we introduce Block AttnRes, which partitions layers into blocks and attends over block-level representations, reducing the memory footprint while preserving most of the gains of full AttnRes. Combined with cache-based pipeline communication and a two-phase computation strategy, Block AttnRes becomes a practical drop-in replacement for standard residual connections with minimal overhead. Scaling law experiments confirm that the improvement is consistent across model sizes, and ablations validate the benefit of content-dependent depth-wise selection. We further integrate AttnRes into the Kimi Linear architecture (48B total / 3B activated parameters) and pre-train on 1.4T tokens, where AttnRes mitigates PreNorm dilution, yielding more uniform output magnitudes and gradient distribution across depth, and improves downstream performance across all evaluated tasks.

moonshotai Moonshot AI
ยท
Mar 16 6

RRWNet: Recursive Refinement Network for effective retinal artery/vein segmentation and classification

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

  • 3 authors
ยท
Feb 5, 2024

ReLi3D: Relightable Multi-view 3D Reconstruction with Disentangled Illumination

Reconstructing 3D assets from images has long required separate pipelines for geometry reconstruction, material estimation, and illumination recovery, each with distinct limitations and computational overhead. We present ReLi3D, the first unified end-to-end pipeline that simultaneously reconstructs complete 3D geometry, spatially-varying physically-based materials, and environment illumination from sparse multi-view images in under one second. Our key insight is that multi-view constraints can dramatically improve material and illumination disentanglement, a problem that remains fundamentally ill-posed for single-image methods. Key to our approach is the fusion of the multi-view input via a transformer cross-conditioning architecture, followed by a novel unified two-path prediction strategy. The first path predicts the object's structure and appearance, while the second path predicts the environment illumination from image background or object reflections. This, combined with a differentiable Monte Carlo multiple importance sampling renderer, creates an optimal illumination disentanglement training pipeline. In addition, with our mixed domain training protocol, which combines synthetic PBR datasets with real-world RGB captures, we establish generalizable results in geometry, material accuracy, and illumination quality. By unifying previously separate reconstruction tasks into a single feed-forward pass, we enable near-instantaneous generation of complete, relightable 3D assets. Project Page: https://reli3d.jdihlmann.com/

StabilityLabs Stability Labs
ยท
Mar 20 2

Generating Drug Repurposing Hypotheses through the Combination of Disease-Specific Hypergraphs

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

  • 5 authors
ยท
Nov 16, 2023

ExposureDiffusion: Learning to Expose for Low-light Image Enhancement

Previous raw image-based low-light image enhancement methods predominantly relied on feed-forward neural networks to learn deterministic mappings from low-light to normally-exposed images. However, they failed to capture critical distribution information, leading to visually undesirable results. This work addresses the issue by seamlessly integrating a diffusion model with a physics-based exposure model. Different from a vanilla diffusion model that has to perform Gaussian denoising, with the injected physics-based exposure model, our restoration process can directly start from a noisy image instead of pure noise. As such, our method obtains significantly improved performance and reduced inference time compared with vanilla diffusion models. To make full use of the advantages of different intermediate steps, we further propose an adaptive residual layer that effectively screens out the side-effect in the iterative refinement when the intermediate results have been already well-exposed. The proposed framework can work with both real-paired datasets, SOTA noise models, and different backbone networks. Note that, the proposed framework is compatible with real-paired datasets, real/synthetic noise models, and different backbone networks. We evaluate the proposed method on various public benchmarks, achieving promising results with consistent improvements using different exposure models and backbones. Besides, the proposed method achieves better generalization capacity for unseen amplifying ratios and better performance than a larger feedforward neural model when few parameters are adopted.

  • 7 authors
ยท
Jul 15, 2023

Graph-Based Self-Healing Tool Routing for Cost-Efficient LLM Agents

Tool-using LLM agents face a reliability-cost tradeoff: routing every decision through the LLM improves correctness but incurs high latency and inference cost, while pre-coded workflow graphs reduce cost but become brittle under unanticipated compound tool failures. We present Self-Healing Router, a fault-tolerant orchestration architecture that treats most agent control-flow decisions as routing rather than reasoning. The system combines (i) parallel health monitors that assign priority scores to runtime conditions such as tool outages and risk signals, and (ii) a cost-weighted tool graph where Dijkstra's algorithm performs deterministic shortest-path routing. When a tool fails mid-execution, its edges are reweighted to infinity and the path is recomputed -- yielding automatic recovery without invoking the LLM. The LLM is reserved exclusively for cases where no feasible path exists, enabling goal demotion or escalation. Prior graph-based tool-use systems (ControlLLM, ToolNet, NaviAgent) focus on tool selection and planning; our contribution is runtime fault tolerance with deterministic recovery and binary observability -- every failure is either a logged reroute or an explicit escalation, never a silent skip. Across 19 scenarios spanning three graph topologies (linear pipeline, dependency DAG, parallel fan-out), Self-Healing Router matches ReAct's correctness while reducing control-plane LLM calls by 93% (9 vs 123 aggregate) and eliminating the silent-failure cases observed in a well-engineered static workflow baseline under compound failures.

  • 1 authors
ยท
Mar 2

Unleashing Scientific Reasoning for Bio-experimental Protocol Generation via Structured Component-based Reward Mechanism

The foundation of reproducible science lies in protocols that are precise, logically ordered, and executable. The autonomous generation of these protocols through natural language queries could greatly improve the efficiency of the reproduction process. However, current leading large language models (LLMs) often generate incomplete or inconsistent protocols, limiting their utility. To address this limitation, we first introduce SciRecipe, a large-scale dataset of over 12K structured protocols spanning 27 biological subfields and encompassing both comprehension and problem-solving tasks. To further improve protocol generation, we propose the "Sketch-and-Fill" paradigm, which separates analysis, structuring, and expression to ensure each step is explicit and verifiable. Complementing this, the structured component-based reward mechanism evaluates step granularity, action order, and semantic fidelity, aligning model optimization with experimental reliability. Building on these components, we develop Thoth, trained through a staged Knowledge-to-Action process that progresses from knowledge acquisition to operational reasoning and ultimately to robust, executable protocol generation. Across multiple benchmarks, Thoth consistently surpasses both proprietary and open-source LLMs, achieving significant improvements in step alignment, logical sequencing, and semantic accuracy. Our approach paves the way for reliable scientific assistants that bridge knowledge with experimental execution. All data, code, and models will be released publicly.

  • 11 authors
ยท
Oct 17, 2025 2

SCORE: Replacing Layer Stacking with Contractive Recurrent Depth

Residual connections are central to modern deep neural networks, enabling stable optimization and efficient information flow across depth. In this work, we propose SCORE (Skip-Connection ODE Recurrent Embedding), a discrete recurrent alternative to classical layer stacking. Instead of composing multiple independent layers, SCORE iteratively applies a single shared neural block using an ODE (Ordinary Differential Equation)-inspired contractive update: ht+1 = (1 - dt) * ht + dt * F(ht) This formulation can be interpreted as a depth-by-iteration refinement process, where the step size dt explicitly controls stability and update magnitude. Unlike continuous Neural ODE approaches, SCORE uses a fixed number of discrete iterations and standard backpropagation without requiring ODE solvers or adjoint methods. We evaluate SCORE across graph neural networks (ESOL molecular solubility), multilayer perceptrons, and Transformer-based language models (nanoGPT). Across architectures, SCORE generally improves convergence speed and often accelerates training. SCORE is reducing parameter count through shared weights. In practice, simple Euler integration provides the best trade-off between computational cost and performance, while higher-order integrators yield marginal gains at increased compute. These results suggest that controlled recurrent depth with contractive residual updates offers a lightweight and effective alternative to classical stacking in deep neural networks.

  • 1 authors
ยท
Mar 11

Make Deep Networks Shallow Again

Deep neural networks have a good success record and are thus viewed as the best architecture choice for complex applications. Their main shortcoming has been, for a long time, the vanishing gradient which prevented the numerical optimization algorithms from acceptable convergence. A breakthrough has been achieved by the concept of residual connections -- an identity mapping parallel to a conventional layer. This concept is applicable to stacks of layers of the same dimension and substantially alleviates the vanishing gradient problem. A stack of residual connection layers can be expressed as an expansion of terms similar to the Taylor expansion. This expansion suggests the possibility of truncating the higher-order terms and receiving an architecture consisting of a single broad layer composed of all initially stacked layers in parallel. In other words, a sequential deep architecture is substituted by a parallel shallow one. Prompted by this theory, we investigated the performance capabilities of the parallel architecture in comparison to the sequential one. The computer vision datasets MNIST and CIFAR10 were used to train both architectures for a total of 6912 combinations of varying numbers of convolutional layers, numbers of filters, kernel sizes, and other meta parameters. Our findings demonstrate a surprising equivalence between the deep (sequential) and shallow (parallel) architectures. Both layouts produced similar results in terms of training and validation set loss. This discovery implies that a wide, shallow architecture can potentially replace a deep network without sacrificing performance. Such substitution has the potential to simplify network architectures, improve optimization efficiency, and accelerate the training process.

  • 3 authors
ยท
Sep 15, 2023

VISTA-PATH: An interactive foundation model for pathology image segmentation and quantitative analysis in computational pathology

Accurate semantic segmentation for histopathology image is crucial for quantitative tissue analysis and downstream clinical modeling. Recent segmentation foundation models have improved generalization through large-scale pretraining, yet remain poorly aligned with pathology because they treat segmentation as a static visual prediction task. Here we present VISTA-PATH, an interactive, class-aware pathology segmentation foundation model designed to resolve heterogeneous structures, incorporate expert feedback, and produce pixel-level segmentation that are directly meaningful for clinical interpretation. VISTA-PATH jointly conditions segmentation on visual context, semantic tissue descriptions, and optional expert-provided spatial prompts, enabling precise multi-class segmentation across heterogeneous pathology images. To support this paradigm, we curate VISTA-PATH Data, a large-scale pathology segmentation corpus comprising over 1.6 million image-mask-text triplets spanning 9 organs and 93 tissue classes. Across extensive held-out and external benchmarks, VISTA-PATH consistently outperforms existing segmentation foundation models. Importantly, VISTA-PATH supports dynamic human-in-the-loop refinement by propagating sparse, patch-level bounding-box annotation feedback into whole-slide segmentation. Finally, we show that the high-fidelity, class-aware segmentation produced by VISTA-PATH is a preferred model for computational pathology. It improve tissue microenvironment analysis through proposed Tumor Interaction Score (TIS), which exhibits strong and significant associations with patient survival. Together, these results establish VISTA-PATH as a foundation model that elevates pathology image segmentation from a static prediction to an interactive and clinically grounded representation for digital pathology. Source code and demo can be found at https://github.com/zhihuanglab/VISTA-PATH.

zhihuanglab Zhi Huang Lab
ยท
Jan 23 3

SFT or RL? An Early Investigation into Training R1-Like Reasoning Large Vision-Language Models

This work revisits the dominant supervised fine-tuning (SFT) then reinforcement learning (RL) paradigm for training Large Vision-Language Models (LVLMs), and reveals a key finding: SFT can significantly undermine subsequent RL by inducing ``pseudo reasoning paths'' imitated from expert models. While these paths may resemble the native reasoning paths of RL models, they often involve prolonged, hesitant, less informative steps, and incorrect reasoning. To systematically study this effect, we introduce VLAA-Thinking, a new multimodal dataset designed to support reasoning in LVLMs. Constructed via a six-step pipeline involving captioning, reasoning distillation, answer rewrite and verification, VLAA-Thinking comprises high-quality, step-by-step visual reasoning traces for SFT, along with a more challenging RL split from the same data source. Using this dataset, we conduct extensive experiments comparing SFT, RL and their combinations. Results show that while SFT helps models learn reasoning formats, it often locks aligned models into imitative, rigid reasoning modes that impede further learning. In contrast, building on the Group Relative Policy Optimization (GRPO) with a novel mixed reward module integrating both perception and cognition signals, our RL approach fosters more genuine, adaptive reasoning behavior. Notably, our model VLAA-Thinker, based on Qwen2.5VL 3B, achieves top-1 performance on Open LMM Reasoning Leaderboard (https://huggingface.co/spaces/opencompass/Open_LMM_Reasoning_Leaderboard) among 4B scale LVLMs, surpassing the previous state-of-the-art by 1.8%. We hope our findings provide valuable insights in developing reasoning-capable LVLMs and can inform future research in this area.

  • 8 authors
ยท
Apr 10, 2025 2

Temporal Residual Guided Diffusion Framework for Event-Driven Video Reconstruction

Event-based video reconstruction has garnered increasing attention due to its advantages, such as high dynamic range and rapid motion capture capabilities. However, current methods often prioritize the extraction of temporal information from continuous event flow, leading to an overemphasis on low-frequency texture features in the scene, resulting in over-smoothing and blurry artifacts. Addressing this challenge necessitates the integration of conditional information, encompassing temporal features, low-frequency texture, and high-frequency events, to guide the Denoising Diffusion Probabilistic Model (DDPM) in producing accurate and natural outputs. To tackle this issue, we introduce a novel approach, the Temporal Residual Guided Diffusion Framework, which effectively leverages both temporal and frequency-based event priors. Our framework incorporates three key conditioning modules: a pre-trained low-frequency intensity estimation module, a temporal recurrent encoder module, and an attention-based high-frequency prior enhancement module. In order to capture temporal scene variations from the events at the current moment, we employ a temporal-domain residual image as the target for the diffusion model. Through the combination of these three conditioning paths and the temporal residual framework, our framework excels in reconstructing high-quality videos from event flow, mitigating issues such as artifacts and over-smoothing commonly observed in previous approaches. Extensive experiments conducted on multiple benchmark datasets validate the superior performance of our framework compared to prior event-based reconstruction methods.

  • 6 authors
ยท
Jul 15, 2024

ERTACache: Error Rectification and Timesteps Adjustment for Efficient Diffusion

Diffusion models suffer from substantial computational overhead due to their inherently iterative inference process. While feature caching offers a promising acceleration strategy by reusing intermediate outputs across timesteps, naive reuse often incurs noticeable quality degradation. In this work, we formally analyze the cumulative error introduced by caching and decompose it into two principal components: feature shift error, caused by inaccuracies in cached outputs, and step amplification error, which arises from error propagation under fixed timestep schedules. To address these issues, we propose ERTACache, a principled caching framework that jointly rectifies both error types. Our method employs an offline residual profiling stage to identify reusable steps, dynamically adjusts integration intervals via a trajectory-aware correction coefficient, and analytically approximates cache-induced errors through a closed-form residual linearization model. Together, these components enable accurate and efficient sampling under aggressive cache reuse. Extensive experiments across standard image and video generation benchmarks show that ERTACache achieves up to 2x inference speedup while consistently preserving or even improving visual quality. Notably, on the state-of-the-art Wan2.1 video diffusion model, ERTACache delivers 2x acceleration with minimal VBench degradation, effectively maintaining baseline fidelity while significantly improving efficiency. The code is available at https://github.com/bytedance/ERTACache.

  • 9 authors
ยท
Aug 27, 2025

K-Paths: Reasoning over Graph Paths for Drug Repurposing and Drug Interaction Prediction

Drug discovery is a complex and time-intensive process that requires identifying and validating new therapeutic candidates. Computational approaches using large-scale biomedical knowledge graphs (KGs) offer a promising solution to accelerate this process. However, extracting meaningful insights from large-scale KGs remains challenging due to the complexity of graph traversal. Existing subgraph-based methods are tailored to graph neural networks (GNNs), making them incompatible with other models, such as large language models (LLMs). We introduce K-Paths, a retrieval framework that extracts structured, diverse, and biologically meaningful paths from KGs. Integrating these paths enables LLMs and GNNs to effectively predict unobserved drug-drug and drug-disease interactions. Unlike traditional path-ranking approaches, K-Paths retrieves and transforms paths into a structured format that LLMs can directly process, facilitating explainable reasoning. K-Paths employs a diversity-aware adaptation of Yen's algorithm to retrieve the K shortest loopless paths between entities in an interaction query, prioritizing biologically relevant and diverse relationships. Our experiments on benchmark datasets show that K-Paths improves the zero-shot performance of Llama 8.1B's F1-score by 12.45 points on drug repurposing and 13.42 points on interaction severity prediction. We also show that Llama 70B achieves F1-score gains of 6.18 and 8.46 points, respectively. K-Paths also improves the supervised training efficiency of EmerGNN, a state-of-the-art GNN, by reducing KG size by 90% while maintaining strong predictive performance. Beyond its scalability and efficiency, K-Paths uniquely bridges the gap between KGs and LLMs, providing explainable rationales for predicted interactions. These capabilities show that K-Paths is a valuable tool for efficient data-driven drug discovery.

  • 7 authors
ยท
Feb 18, 2025

LAMMI-Pathology: A Tool-Centric Bottom-Up LVLM-Agent Framework for Molecularly Informed Medical Intelligence in Pathology

The emergence of tool-calling-based agent systems introduces a more evidence-driven paradigm for pathology image analysis in contrast to the coarse-grained text-image diagnostic approaches. With the recent large-scale experimental adoption of spatial transcriptomics technologies, molecularly validated pathological diagnosis is becoming increasingly open and accessible. In this work, we propose LAMMI-Pathology (LVLM-Agent System for Molecularly Informed Medical Intelligence in Pathology), a scalable agent framework for domain-specific agent tool-calling. LAMMI-Pathology adopts a tool-centric, bottom-up architecture in which customized domain-adaptive tools serve as the foundation. These tools are clustered by domain style to form component agents, which are then coordinated through a top-level planner hierarchically, avoiding excessively long context lengths that could induce task drift. Based on that, we introduce a novel trajectory construction mechanism based on Atomic Execution Nodes (AENs), which serve as reliable and composable units for building semi-simulated reasoning trajectories that capture credible agent-tool interactions. Building on this foundation, we develop a trajectory-aware fine-tuning strategy that aligns the planner's decision-making process with these multi-step reasoning trajectories, thereby enhancing inference robustness in pathology understanding and its adaptive use of the customized toolset.

  • 3 authors
ยท
Feb 21

TRIP: Temporal Residual Learning with Image Noise Prior for Image-to-Video Diffusion Models

Recent advances in text-to-video generation have demonstrated the utility of powerful diffusion models. Nevertheless, the problem is not trivial when shaping diffusion models to animate static image (i.e., image-to-video generation). The difficulty originates from the aspect that the diffusion process of subsequent animated frames should not only preserve the faithful alignment with the given image but also pursue temporal coherence among adjacent frames. To alleviate this, we present TRIP, a new recipe of image-to-video diffusion paradigm that pivots on image noise prior derived from static image to jointly trigger inter-frame relational reasoning and ease the coherent temporal modeling via temporal residual learning. Technically, the image noise prior is first attained through one-step backward diffusion process based on both static image and noised video latent codes. Next, TRIP executes a residual-like dual-path scheme for noise prediction: 1) a shortcut path that directly takes image noise prior as the reference noise of each frame to amplify the alignment between the first frame and subsequent frames; 2) a residual path that employs 3D-UNet over noised video and static image latent codes to enable inter-frame relational reasoning, thereby easing the learning of the residual noise for each frame. Furthermore, both reference and residual noise of each frame are dynamically merged via attention mechanism for final video generation. Extensive experiments on WebVid-10M, DTDB and MSR-VTT datasets demonstrate the effectiveness of our TRIP for image-to-video generation. Please see our project page at https://trip-i2v.github.io/TRIP/.

  • 7 authors
ยท
Mar 25, 2024 1

A Model RRNet for Spectral Information Exploitation and LAMOST Medium-resolution Spectrum Parameter Estimation

This work proposes a Residual Recurrent Neural Network (RRNet) for synthetically extracting spectral information, and estimating stellar atmospheric parameters together with 15 chemical element abundances for medium-resolution spectra from Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST). The RRNet consists of two fundamental modules: a residual module and a recurrent module. The residual module extracts spectral features based on the longitudinally driving power from parameters, while the recurrent module recovers spectral information and restrains the negative influences from noises based on Cross-band Belief Enhancement. RRNet is trained by the spectra from common stars between LAMOST DR7 and APOGEE-Payne catalog. The 17 stellar parameters and their uncertainties for 2.37 million medium-resolution spectra from LAMOST DR7 are predicted. For spectra with S/N >= 10, the precision of estimations Teff and log g are 88 K and 0.13 dex respectively, elements C, Mg, Al, Si, Ca, Fe, Ni are 0.05 dex to 0.08 dex, and N, O, S, K, Ti, Cr, Mn are 0.09 dex to 0.14 dex, while that of Cu is 0.19 dex. Compared with StarNet and SPCANet, RRNet shows higher accuracy and robustness. In comparison to Apache Point Observatory Galactic Evolution Experiment and Galactic Archaeology with HERMES surveys, RRNet manifests good consistency within a reasonable range of bias. Finally, this work releases a catalog for 2.37 million medium-resolution spectra from the LAMOST DR7, the source code, the trained model and the experimental data respectively for astronomical science exploration and data processing algorithm research reference.

  • 3 authors
ยท
May 30, 2022

PathGen-1.6M: 1.6 Million Pathology Image-text Pairs Generation through Multi-agent Collaboration

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

  • 10 authors
ยท
Jun 28, 2024

ReinFlow: Fine-tuning Flow Matching Policy with Online Reinforcement Learning

We propose ReinFlow, a simple yet effective online reinforcement learning (RL) framework that fine-tunes a family of flow matching policies for continuous robotic control. Derived from rigorous RL theory, ReinFlow injects learnable noise into a flow policy's deterministic path, converting the flow into a discrete-time Markov Process for exact and straightforward likelihood computation. This conversion facilitates exploration and ensures training stability, enabling ReinFlow to fine-tune diverse flow model variants, including Rectified Flow [35] and Shortcut Models [19], particularly at very few or even one denoising step. We benchmark ReinFlow in representative locomotion and manipulation tasks, including long-horizon planning with visual input and sparse reward. The episode reward of Rectified Flow policies obtained an average net growth of 135.36% after fine-tuning in challenging legged locomotion tasks while saving denoising steps and 82.63% of wall time compared to state-of-the-art diffusion RL fine-tuning method DPPO [43]. The success rate of the Shortcut Model policies in state and visual manipulation tasks achieved an average net increase of 40.34% after fine-tuning with ReinFlow at four or even one denoising step, whose performance is comparable to fine-tuned DDIM policies while saving computation time for an average of 23.20%. Project webpage: https://reinflow.github.io/

  • 4 authors
ยท
May 28, 2025

Resfusion: Denoising Diffusion Probabilistic Models for Image Restoration Based on Prior Residual Noise

Recently, research on denoising diffusion models has expanded its application to the field of image restoration. Traditional diffusion-based image restoration methods utilize degraded images as conditional input to effectively guide the reverse generation process, without modifying the original denoising diffusion process. However, since the degraded images already include low-frequency information, starting from Gaussian white noise will result in increased sampling steps. We propose Resfusion, a general framework that incorporates the residual term into the diffusion forward process, starting the reverse process directly from the noisy degraded images. The form of our inference process is consistent with the DDPM. We introduced a weighted residual noise, named resnoise, as the prediction target and explicitly provide the quantitative relationship between the residual term and the noise term in resnoise. By leveraging a smooth equivalence transformation, Resfusion determine the optimal acceleration step and maintains the integrity of existing noise schedules, unifying the training and inference processes. The experimental results demonstrate that Resfusion exhibits competitive performance on ISTD dataset, LOL dataset and Raindrop dataset with only five sampling steps. Furthermore, Resfusion can be easily applied to image generation and emerges with strong versatility. Our code and model are available at https://github.com/nkicsl/Resfusion.

  • 9 authors
ยท
Nov 24, 2023

KromHC: Manifold-Constrained Hyper-Connections with Kronecker-Product Residual Matrices

The success of Hyper-Connections (HC) in neural networks (NN) has also highlighted issues related to its training instability and restricted scalability. The Manifold-Constrained Hyper-Connections (mHC) mitigate these challenges by projecting the residual connection space onto a Birkhoff polytope, however, it faces two issues: 1) its iterative Sinkhorn-Knopp (SK) algorithm does not always yield exact doubly stochastic residual matrices; 2) mHC incurs a prohibitive O(n^3C) parameter complexity with n as the width of the residual stream and C as the feature dimension. The recently proposed mHC-lite reparametrizes the residual matrix via the Birkhoff-von-Neumann theorem to guarantee double stochasticity, but also faces a factorial explosion in its parameter complexity, O left( nC cdot n! right). To address both challenges, we propose KromHC, which uses the Kronecker products of smaller doubly stochastic matrices to parametrize the residual matrix in mHC. By enforcing manifold constraints across the factor residual matrices along each mode of the tensorized residual stream, KromHC guarantees exact double stochasticity of the residual matrices while reducing parameter complexity to O(n^2C). Comprehensive experiments demonstrate that KromHC matches or even outperforms state-of-the-art (SOTA) mHC variants, while requiring significantly fewer trainable parameters. The code is available at https://github.com/wz1119/KromHC.

  • 4 authors
ยท
Jan 29 5

WorldForge: Unlocking Emergent 3D/4D Generation in Video Diffusion Model via Training-Free Guidance

Recent video diffusion models demonstrate strong potential in spatial intelligence tasks due to their rich latent world priors. However, this potential is hindered by their limited controllability and geometric inconsistency, creating a gap between their strong priors and their practical use in 3D/4D tasks. As a result, current approaches often rely on retraining or fine-tuning, which risks degrading pretrained knowledge and incurs high computational costs. To address this, we propose WorldForge, a training-free, inference-time framework composed of three tightly coupled modules. Intra-Step Recursive Refinement introduces a recursive refinement mechanism during inference, which repeatedly optimizes network predictions within each denoising step to enable precise trajectory injection. Flow-Gated Latent Fusion leverages optical flow similarity to decouple motion from appearance in the latent space and selectively inject trajectory guidance into motion-related channels. Dual-Path Self-Corrective Guidance compares guided and unguided denoising paths to adaptively correct trajectory drift caused by noisy or misaligned structural signals. Together, these components inject fine-grained, trajectory-aligned guidance without training, achieving both accurate motion control and photorealistic content generation. Extensive experiments across diverse benchmarks validate our method's superiority in realism, trajectory consistency, and visual fidelity. This work introduces a novel plug-and-play paradigm for controllable video synthesis, offering a new perspective on leveraging generative priors for spatial intelligence.

  • 5 authors
ยท
Sep 18, 2025 7

Agent-R: Training Language Model Agents to Reflect via Iterative Self-Training

Large Language Models (LLMs) agents are increasingly pivotal for addressing complex tasks in interactive environments. Existing work mainly focuses on enhancing performance through behavior cloning from stronger experts, yet such approaches often falter in real-world applications, mainly due to the inability to recover from errors. However, step-level critique data is difficult and expensive to collect. Automating and dynamically constructing self-critique datasets is thus crucial to empowering models with intelligent agent capabilities. In this work, we propose an iterative self-training framework, Agent-R, that enables language Agent to Reflect on the fly. Unlike traditional methods that reward or penalize actions based on correctness, Agent-R leverages MCTS to construct training data that recover correct trajectories from erroneous ones. A key challenge of agent reflection lies in the necessity for timely revision rather than waiting until the end of a rollout. To address this, we introduce a model-guided critique construction mechanism: the actor model identifies the first error step (within its current capability) in a failed trajectory. Starting from it, we splice it with the adjacent correct path, which shares the same parent node in the tree. This strategy enables the model to learn reflection based on its current policy, therefore yielding better learning efficiency. To further explore the scalability of this self-improvement paradigm, we investigate iterative refinement of both error correction capabilities and dataset construction. Our findings demonstrate that Agent-R continuously improves the model's ability to recover from errors and enables timely error correction. Experiments on three interactive environments show that Agent-R effectively equips agents to correct erroneous actions while avoiding loops, achieving superior performance compared to baseline methods (+5.59%).

  • 6 authors
ยท
Jan 20, 2025 2

RAP-SR: RestorAtion Prior Enhancement in Diffusion Models for Realistic Image Super-Resolution

Benefiting from their powerful generative capabilities, pretrained diffusion models have garnered significant attention for real-world image super-resolution (Real-SR). Existing diffusion-based SR approaches typically utilize semantic information from degraded images and restoration prompts to activate prior for producing realistic high-resolution images. However, general-purpose pretrained diffusion models, not designed for restoration tasks, often have suboptimal prior, and manually defined prompts may fail to fully exploit the generated potential. To address these limitations, we introduce RAP-SR, a novel restoration prior enhancement approach in pretrained diffusion models for Real-SR. First, we develop the High-Fidelity Aesthetic Image Dataset (HFAID), curated through a Quality-Driven Aesthetic Image Selection Pipeline (QDAISP). Our dataset not only surpasses existing ones in fidelity but also excels in aesthetic quality. Second, we propose the Restoration Priors Enhancement Framework, which includes Restoration Priors Refinement (RPR) and Restoration-Oriented Prompt Optimization (ROPO) modules. RPR refines the restoration prior using the HFAID, while ROPO optimizes the unique restoration identifier, improving the quality of the resulting images. RAP-SR effectively bridges the gap between general-purpose models and the demands of Real-SR by enhancing restoration prior. Leveraging the plug-and-play nature of RAP-SR, our approach can be seamlessly integrated into existing diffusion-based SR methods, boosting their performance. Extensive experiments demonstrate its broad applicability and state-of-the-art results. Codes and datasets will be available upon acceptance.

  • 6 authors
ยท
Dec 9, 2024

ST-ResGAT: Explainable Spatio-Temporal Graph Neural Network for Road Condition Prediction and Priority-Driven Maintenance

Climate-vulnerable road networks require a paradigm shift from reactive, fix-on-failure repairs to predictive, decision-ready maintenance. This paper introduces ST-ResGAT, a novel Spatio-Temporal Residual Graph Attention Network that fuses residual graph-attention encoding with GRU temporal aggregation to forecast pavement deterioration. Engineered for resource-constrained deployment, the framework translates continuous Pavement Condition Index (PCI) forecasts directly into the American Society for Testing and Materials (ASTM)-compliant maintenance priorities. Using a real-world inspection dataset of 750 segments in Sylhet, Bangladesh (2021-2024), ST-ResGAT significantly outperforms traditional non-spatial machine learning baselines, achieving exceptional predictive fidelity (R2 = 0.93, RMSE = 2.72). Crucially, ablation testing confirmed the mathematical necessity of modeling topological neighbor effects, proving that structural decay acts as a spatial contagion. Uniquely, we integrate GNNExplainer to unbox the model, demonstrating that its learned priorities align perfectly with established physical engineering theory. Furthermore, we quantify classification safety: achieving 85.5% exact ASTM class agreement and 100% adjacent-class containment, ensuring bounded, engineer-safe predictions. To connect model outputs to policy, we generate localized longitudinal maintenance profiles, perform climate stress-testing, and derive Pareto sustainability frontiers. ST-ResGAT therefore offers a practical, explainable, and sustainable blueprint for intelligent infrastructure management in high-risk, low-resource geological settings.

  • 4 authors
ยท
Mar 14

A protocol for evaluating robustness to H&E staining variation in computational pathology models

Sensitivity to staining variation remains a major barrier to deploying computational pathology (CPath) models as hematoxylin and eosin (H&E) staining varies across laboratories, requiring systematic assessment of how this variability affects model prediction. In this work, we developed a three-step protocol for evaluating robustness to H&E staining variation in CPath models. Step 1: Select reference staining conditions, Step 2: Characterize test set staining properties, Step 3: Apply CPath model(s) under simulated reference staining conditions. Here, we first created a new reference staining library based on the PLISM dataset. As an exemplary use case, we applied the protocol to assess the robustness properties of 306 microsatellite instability (MSI) classification models on the unseen SurGen colorectal cancer dataset (n=738), including 300 attention-based multiple instance learning models trained on the TCGA-COAD/READ datasets across three feature extractors (UNI2-h, H-Optimus-1, Virchow2), alongside six public MSI classification models. Classification performance was measured as AUC, and robustness as the min-max AUC range across four simulated staining conditions (low/high H&E intensity, low/high H&E color similarity). Across models and staining conditions, classification performance ranged from AUC 0.769-0.911 (ฮ” = 0.142). Robustness ranged from 0.007-0.079 (ฮ” = 0.072), and showed a weak inverse correlation with classification performance (Pearson r=-0.22, 95% CI [-0.34, -0.11]). Thus, we show that the proposed evaluation protocol enables robustness-informed CPath model selection and provides insight into performance shifts across H&E staining conditions, supporting the identification of operational ranges for reliable model deployment. Code is available at https://github.com/CTPLab/staining-robustness-evaluation .

  • 8 authors
ยท
Mar 13

IRepair: An Intent-Aware Approach to Repair Data-Driven Errors in Large Language Models

Not a day goes by without hearing about the impressive feats of large language models (LLMs), and equally, not a day passes without hearing about their challenges. LLMs are notoriously vulnerable to biases in their dataset, leading to issues such as toxicity. While domain-adaptive training has been employed to mitigate these issues, these techniques often address all model parameters indiscriminately during the repair process, resulting in poor repair quality and reduced model versatility. In this paper, we introduce a novel dynamic slicing-based intent-aware LLM repair strategy, IRepair. This approach selectively targets the most error-prone sections of the model for repair. Specifically, we propose dynamically slicing the model's most sensitive layers that require immediate attention, concentrating repair efforts on those areas. This method enables more effective repairs with potentially less impact on the model's overall performance by altering a smaller portion of the model. We evaluated our technique on three models from the GPT2 and GPT-Neo families, with parameters ranging from 800M to 1.6B, in a toxicity mitigation setup. Our results show that IRepair repairs errors 43.6% more effectively while causing 46% less disruption to general performance compared to the closest baseline, direct preference optimization. Our empirical analysis also reveals that errors are more concentrated in a smaller section of the model, with the top 20% of layers exhibiting 773% more error density than the remaining 80\%. This highlights the need for selective repair. Additionally, we demonstrate that a dynamic selection approach is essential for addressing errors dispersed throughout the model, ensuring a robust and efficient repair.

  • 4 authors
ยท
Feb 10, 2025

Diffusion-based Extreme Image Compression with Compressed Feature Initialization

Diffusion-based extreme image compression methods have achieved impressive performance at extremely low bitrates. However, constrained by the iterative denoising process that starts from pure noise, these methods are limited in both fidelity and efficiency. To address these two issues, we present Relay Residual Diffusion Extreme Image Compression (RDEIC), which leverages compressed feature initialization and residual diffusion. Specifically, we first use the compressed latent features of the image with added noise, instead of pure noise, as the starting point to eliminate the unnecessary initial stages of the denoising process. Second, we design a novel relay residual diffusion that reconstructs the raw image by iteratively removing the added noise and the residual between the compressed and target latent features. Notably, our relay residual diffusion network seamlessly integrates pre-trained stable diffusion to leverage its robust generative capability for high-quality reconstruction. Third, we propose a fixed-step fine-tuning strategy to eliminate the discrepancy between the training and inference phases, further improving the reconstruction quality. Extensive experiments demonstrate that the proposed RDEIC achieves state-of-the-art visual quality and outperforms existing diffusion-based extreme image compression methods in both fidelity and efficiency. The source code will be provided in https://github.com/huai-chang/RDEIC.

  • 5 authors
ยท
Oct 3, 2024

Poincarรฉ ResNet

This paper introduces an end-to-end residual network that operates entirely on the Poincar\'e ball model of hyperbolic space. Hyperbolic learning has recently shown great potential for visual understanding, but is currently only performed in the penultimate layer(s) of deep networks. All visual representations are still learned through standard Euclidean networks. In this paper we investigate how to learn hyperbolic representations of visual data directly from the pixel-level. We propose Poincar\'e ResNet, a hyperbolic counterpart of the celebrated residual network, starting from Poincar\'e 2D convolutions up to Poincar\'e residual connections. We identify three roadblocks for training convolutional networks entirely in hyperbolic space and propose a solution for each: (i) Current hyperbolic network initializations collapse to the origin, limiting their applicability in deeper networks. We provide an identity-based initialization that preserves norms over many layers. (ii) Residual networks rely heavily on batch normalization, which comes with expensive Fr\'echet mean calculations in hyperbolic space. We introduce Poincar\'e midpoint batch normalization as a faster and equally effective alternative. (iii) Due to the many intermediate operations in Poincar\'e layers, we lastly find that the computation graphs of deep learning libraries blow up, limiting our ability to train on deep hyperbolic networks. We provide manual backward derivations of core hyperbolic operations to maintain manageable computation graphs.

  • 3 authors
ยท
Mar 24, 2023

Do Language Models Use Their Depth Efficiently?

Modern LLMs are increasingly deep, and depth correlates with performance, albeit with diminishing returns. However, do these models use their depth efficiently? Do they compose more features to create higher-order computations that are impossible in shallow models, or do they merely spread the same kinds of computation out over more layers? To address these questions, we analyze the residual stream of the Llama 3.1 and Qwen 3 family of models. We find: First, comparing the output of the sublayers to the residual stream reveals that layers in the second half contribute much less than those in the first half, with a clear phase transition between the two halves. Second, skipping layers in the second half has a much smaller effect on future computations and output predictions. Third, for multihop tasks, we are unable to find evidence that models are using increased depth to compose subresults in examples involving many hops. Fourth, we seek to directly address whether deeper models are using their additional layers to perform new kinds of computation. To do this, we train linear maps from the residual stream of a shallow model to a deeper one. We find that layers with the same relative depth map best to each other, suggesting that the larger model simply spreads the same computations out over its many layers. All this evidence suggests that deeper models are not using their depth to learn new kinds of computation, but only using the greater depth to perform more fine-grained adjustments to the residual. This may help explain why increasing scale leads to diminishing returns for stacked Transformer architectures.

  • 3 authors
ยท
May 20, 2025

Transform-Invariant Generative Ray Path Sampling for Efficient Radio Propagation Modeling

Ray tracing has become a standard for accurate radio propagation modeling, but suffers from exponential computational complexity, as the number of candidate paths scales with the number of objects raised to the power of the interaction order. This bottleneck limits its use in large-scale or real-time applications, forcing traditional tools to rely on heuristics to reduce the number of path candidates at the cost of potentially reduced accuracy. To overcome this limitation, we propose a comprehensive machine-learning-assisted framework that replaces exhaustive path searching with intelligent sampling via Generative Flow Networks. Applying such generative models to this domain presents significant challenges, particularly sparse rewards due to the rarity of valid paths, which can lead to convergence failures and trivial solutions when evaluating high-order interactions in complex environments. To ensure robust learning and efficient exploration, our framework incorporates three key architectural components. First, we implement an experience replay buffer to capture and retain rare valid paths. Second, we adopt a uniform exploratory policy to improve generalization and prevent the model from overfitting to simple geometries. Third, we apply a physics-based action masking strategy that filters out physically impossible paths before the model even considers them. As demonstrated in our experimental validation, the proposed model achieves substantial speedups over exhaustive search -- up to 10times faster on GPU and 1000times faster on CPU -- while maintaining high coverage accuracy and successfully uncovering complex propagation paths. The complete source code, tests, and tutorial are available at https://github.com/jeertmans/sampling-paths.

EXAONE Path 2.5: Pathology Foundation Model with Multi-Omics Alignment

Cancer progression arises from interactions across multiple biological layers, especially beyond morphological and across molecular layers that remain invisible to image-only models. To capture this broader biological landscape, we present EXAONE Path 2.5, a pathology foundation model that jointly models histologic, genomic, epigenetic and transcriptomic modalities, producing an integrated patient representation that reflects tumor biology more comprehensively. Our approach incorporates three key components: (1) multimodal SigLIP loss enabling all-pairwise contrastive learning across heterogeneous modalities, (2) a fragment-aware rotary positional encoding (F-RoPE) module that preserves spatial structure and tissue-fragment topology in WSI, and (3) domain-specialized internal foundation models for both WSI and RNA-seq to provide biologically grounded embeddings for robust multimodal alignment. We evaluate EXAONE Path 2.5 against six leading pathology foundation models across two complementary benchmarks: an internal real-world clinical dataset and the Patho-Bench benchmark covering 80 tasks. Our framework demonstrates high data and parameter efficiency, achieving on-par performance with state-of-the-art foundation models on Patho-Bench while exhibiting the highest adaptability in the internal clinical setting. These results highlight the value of biologically informed multimodal design and underscore the potential of integrated genotype-to-phenotype modeling for next-generation precision oncology.

  • 7 authors
ยท
Dec 15, 2025

InT: Self-Proposed Interventions Enable Credit Assignment in LLM Reasoning

Outcome-reward reinforcement learning (RL) has proven effective at improving the reasoning capabilities of large language models (LLMs). However, standard RL assigns credit only at the level of the final answer, penalizing entire reasoning traces when the outcome is incorrect and uniformly reinforcing all steps when it is correct. As a result, correct intermediate steps may be discouraged in failed traces, while spurious steps may be reinforced in successful ones. We refer to this failure mode as the problem of credit assignment. While a natural remedy is to train a process reward model, accurately optimizing such models to identify corrective reasoning steps remains challenging. We introduce Intervention Training (InT), a training paradigm in which the model performs fine-grained credit assignment on its own reasoning traces by proposing short, targeted corrections that steer trajectories toward higher reward. Using reference solutions commonly available in mathematical reasoning datasets and exploiting the fact that verifying a model-generated solution is easier than generating a correct one from scratch, the model identifies the first error in its reasoning and proposes a single-step intervention to redirect the trajectory toward the correct solution. We then apply supervised fine-tuning (SFT) to the on-policy rollout up to the point of error concatenated with the intervention, localizing error to the specific step that caused failure. We show that the resulting model serves as a far better initialization for RL training. After running InT and subsequent fine-tuning with RL, we improve accuracy by nearly 14% over a 4B-parameter base model on IMO-AnswerBench, outperforming larger open-source models such as gpt-oss-20b.

Feature Re-Embedding: Towards Foundation Model-Level Performance in Computational Pathology

Multiple instance learning (MIL) is the most widely used framework in computational pathology, encompassing sub-typing, diagnosis, prognosis, and more. However, the existing MIL paradigm typically requires an offline instance feature extractor, such as a pre-trained ResNet or a foundation model. This approach lacks the capability for feature fine-tuning within the specific downstream tasks, limiting its adaptability and performance. To address this issue, we propose a Re-embedded Regional Transformer (R^2T) for re-embedding the instance features online, which captures fine-grained local features and establishes connections across different regions. Unlike existing works that focus on pre-training powerful feature extractor or designing sophisticated instance aggregator, R^2T is tailored to re-embed instance features online. It serves as a portable module that can seamlessly integrate into mainstream MIL models. Extensive experimental results on common computational pathology tasks validate that: 1) feature re-embedding improves the performance of MIL models based on ResNet-50 features to the level of foundation model features, and further enhances the performance of foundation model features; 2) the R^2T can introduce more significant performance improvements to various MIL models; 3) R^2T-MIL, as an R^2T-enhanced AB-MIL, outperforms other latest methods by a large margin.The code is available at: https://github.com/DearCaat/RRT-MIL.

  • 6 authors
ยท
Feb 27, 2024

EoRA: Training-free Compensation for Compressed LLM with Eigenspace Low-Rank Approximation

In this work, we re-formulate the model compression problem into the customized compensation problem: Given a compressed model, we aim to introduce residual low-rank paths to compensate for compression errors under customized requirements from users (e.g., tasks, compression ratios), resulting in greater flexibility in adjusting overall capacity without being constrained by specific compression formats. However, naively applying SVD to derive residual paths causes suboptimal utilization of the low-rank representation capacity. Instead, we propose Training-free Eigenspace Low-Rank Approximation (EoRA), a method that directly minimizes compression-induced errors without requiring gradient-based training, achieving fast optimization in minutes using a small amount of calibration data. EoRA projects compression errors into the eigenspace of input activations, leveraging eigenvalues to effectively prioritize the reconstruction of high-importance error components. Moreover, EoRA can be seamlessly integrated with fine-tuning and quantization to further improve effectiveness and efficiency. EoRA consistently outperforms previous methods in compensating errors for compressed LLaMA2/3 models on various tasks, such as language generation, commonsense reasoning, and math reasoning tasks (e.g., 31.31%/12.88% and 9.69% improvements on ARC-Easy/ARC-Challenge and MathQA when compensating LLaMA3-8B that is quantized to 4-bit and pruned to 2:4 sparsity). EoRA offers a scalable, training-free solution to compensate for compression errors, making it a powerful tool to deploy LLMs in various capacity and efficiency requirements.

nvidia NVIDIA
ยท
Oct 28, 2024 2

RedOne: Revealing Domain-specific LLM Post-Training in Social Networking Services

As a primary medium for modern information dissemination, social networking services (SNS) have experienced rapid growth, which has proposed significant challenges for platform content management and interaction quality improvement. Recently, the development of large language models (LLMs) has offered potential solutions but existing studies focus on isolated tasks, which not only encounter diminishing benefit from the data scaling within individual scenarios but also fail to flexibly adapt to diverse real-world context. To address these challenges, we introduce RedOne, a domain-specific LLM designed to break the performance bottleneck of single-task baselines and establish a comprehensive foundation for the SNS. RedOne was developed through a three-stage training strategy consisting of continue pretraining, supervised fine-tuning, and preference optimization, using a large-scale real-world dataset. Through extensive experiments, RedOne maintains strong general capabilities, and achieves an average improvement up to 14.02% across 8 major SNS tasks and 7.56% in SNS bilingual evaluation benchmark, compared with base models. Furthermore, through online testing, RedOne reduced the exposure rate in harmful content detection by 11.23% and improved the click page rate in post-view search by 14.95% compared with single-tasks finetuned baseline models. These results establish RedOne as a robust domain-specific LLM for SNS, demonstrating excellent generalization across various tasks and promising applicability in real-world scenarios.

  • 25 authors
ยท
Jul 12, 2025 2

Ladder-residual: parallelism-aware architecture for accelerating large model inference with communication overlapping

Large language model inference is both memory-intensive and time-consuming, often requiring distributed algorithms to efficiently scale. Various model parallelism strategies are used in multi-gpu training and inference to partition computation across multiple devices, reducing memory load and computation time. However, using model parallelism necessitates communication of information between GPUs, which has been a major bottleneck and limits the gains obtained by scaling up the number of devices. We introduce Ladder Residual, a simple architectural modification applicable to all residual-based models that enables straightforward overlapping that effectively hides the latency of communication. Our insight is that in addition to systems optimization, one can also redesign the model architecture to decouple communication from computation. While Ladder Residual can allow communication-computation decoupling in conventional parallelism patterns, we focus on Tensor Parallelism in this paper, which is particularly bottlenecked by its heavy communication. For a Transformer model with 70B parameters, applying Ladder Residual to all its layers can achieve 30% end-to-end wall clock speed up at inference time with TP sharding over 8 devices. We refer the resulting Transformer model as the Ladder Transformer. We train a 1B and 3B Ladder Transformer from scratch and observe comparable performance to a standard dense transformer baseline. We also show that it is possible to convert parts of the Llama-3.1 8B model to our Ladder Residual architecture with minimal accuracy degradation by only retraining for 3B tokens.

  • 10 authors
ยท
Jan 11, 2025

RedOne 2.0: Rethinking Domain-specific LLM Post-Training in Social Networking Services

As a key medium for human interaction and information exchange, social networking services (SNS) pose unique challenges for large language models (LLMs): heterogeneous workloads, fast-shifting norms and slang, and multilingual, culturally diverse corpora that induce sharp distribution shift. Supervised fine-tuning (SFT) can specialize models but often triggers a ``seesaw'' between in-distribution gains and out-of-distribution robustness, especially for smaller models. To address these challenges, we introduce RedOne 2.0, an SNS-oriented LLM trained with a progressive, RL-prioritized post-training paradigm designed for rapid and stable adaptation. The pipeline consist in three stages: (1) Exploratory Learning on curated SNS corpora to establish initial alignment and identify systematic weaknesses; (2) Targeted Fine-Tuning that selectively applies SFT to the diagnosed gaps while mixing a small fraction of general data to mitigate forgetting; and (3) Refinement Learning that re-applies RL with SNS-centric signals to consolidate improvements and harmonize trade-offs across tasks. Across various tasks spanning three categories, our 4B scale model delivers an average improvements about 2.41 over the 7B sub-optimal baseline. Additionally, RedOne 2.0 achieves average performance lift about 8.74 from the base model with less than half the data required by SFT-centric method RedOne, evidencing superior data efficiency and stability at compact scales. Overall, RedOne 2.0 establishes a competitive, cost-effective baseline for domain-specific LLMs in SNS scenario, advancing capability without sacrificing robustness.

  • 12 authors
ยท
Nov 10, 2025 2

M2R2: Mixture of Multi-Rate Residuals for Efficient Transformer Inference

Residual transformations enhance the representational depth and expressive power of large language models (LLMs). However, applying static residual transformations across all tokens in auto-regressive generation leads to a suboptimal trade-off between inference efficiency and generation fidelity. Existing methods, including Early Exiting, Skip Decoding, and Mixture-of-Depth address this by modulating the residual transformation based on token-level complexity. Nevertheless, these approaches predominantly consider the distance traversed by tokens through the model layers, neglecting the underlying velocity of residual evolution. We introduce Mixture of Multi-rate Residuals (M2R2), a framework that dynamically modulates residual velocity to improve early alignment, enhancing inference efficiency. Evaluations on reasoning oriented tasks such as Koala, Self-Instruct, WizardLM, and MT-Bench show M2R2 surpasses state-of-the-art distance-based strategies, balancing generation quality and speedup. In self-speculative decoding setup, M2R2 achieves up to 2.8x speedups on MT-Bench, outperforming methods like 2-model speculative decoding, Medusa, LookAhead Decoding, and DEED. In Mixture-of-Experts (MoE) architectures, integrating early residual alignment with ahead-of-time expert loading into high-bandwidth memory (HBM) accelerates decoding, reduces expert-switching bottlenecks, and achieves a 2.9x speedup, making it highly effective in resource-constrained environments.

  • 4 authors
ยท
Feb 4, 2025

REG4Rec: Reasoning-Enhanced Generative Model for Large-Scale Recommendation Systems

Sequential recommendation aims to predict a user's next action in large-scale recommender systems. While traditional methods often suffer from insufficient information interaction, recent generative recommendation models partially address this issue by directly generating item predictions. To better capture user intents, recent studies have introduced a reasoning process into generative recommendation, significantly improving recommendation performance. However, these approaches are constrained by the singularity of item semantic representations, facing challenges such as limited diversity in reasoning pathways and insufficient reliability in the reasoning process. To tackle these issues, we introduce REG4Rec, a reasoning-enhanced generative model that constructs multiple dynamic semantic reasoning paths alongside a self-reflection process, ensuring high-confidence recommendations. Specifically, REG4Rec utilizes an MoE-based parallel quantization codebook (MPQ) to generate multiple unordered semantic tokens for each item, thereby constructing a larger-scale diverse reasoning space. Furthermore, to enhance the reliability of reasoning, we propose a training reasoning enhancement stage, which includes Preference Alignment for Reasoning (PARS) and a Multi-Step Reward Augmentation (MSRA) strategy. PARS uses reward functions tailored for recommendation to enhance reasoning and reflection, while MSRA introduces future multi-step actions to improve overall generalization. During inference, Consistency-Oriented Self-Reflection for Pruning (CORP) is proposed to discard inconsistent reasoning paths, preventing the propagation of erroneous reasoning. Lastly, we develop an efficient offline training strategy for large-scale recommendation. Experiments on real-world datasets and online evaluations show that REG4Rec delivers outstanding performance and substantial practical value.

  • 11 authors
ยท
Aug 21, 2025

Gene-Metabolite Association Prediction with Interactive Knowledge Transfer Enhanced Graph for Metabolite Production

In the rapidly evolving field of metabolic engineering, the quest for efficient and precise gene target identification for metabolite production enhancement presents significant challenges. Traditional approaches, whether knowledge-based or model-based, are notably time-consuming and labor-intensive, due to the vast scale of research literature and the approximation nature of genome-scale metabolic model (GEM) simulations. Therefore, we propose a new task, Gene-Metabolite Association Prediction based on metabolic graphs, to automate the process of candidate gene discovery for a given pair of metabolite and candidate-associated genes, as well as presenting the first benchmark containing 2474 metabolites and 1947 genes of two commonly used microorganisms Saccharomyces cerevisiae (SC) and Issatchenkia orientalis (IO). This task is challenging due to the incompleteness of the metabolic graphs and the heterogeneity among distinct metabolisms. To overcome these limitations, we propose an Interactive Knowledge Transfer mechanism based on Metabolism Graph (IKT4Meta), which improves the association prediction accuracy by integrating the knowledge from different metabolism graphs. First, to build a bridge between two graphs for knowledge transfer, we utilize Pretrained Language Models (PLMs) with external knowledge of genes and metabolites to help generate inter-graph links, significantly alleviating the impact of heterogeneity. Second, we propagate intra-graph links from different metabolic graphs using inter-graph links as anchors. Finally, we conduct the gene-metabolite association prediction based on the enriched metabolism graphs, which integrate the knowledge from multiple microorganisms. Experiments on both types of organisms demonstrate that our proposed methodology outperforms baselines by up to 12.3% across various link prediction frameworks.

  • 6 authors
ยท
Oct 24, 2024