Daily Papers

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Cell painting is a popular technique for creating human-interpretable, high-contrast images of cell morphology. There are two major issues with cell paint: (1) it is labor-intensive and (2) it requires chemical fixation, making the study of cell dynamics impossible. We train a diffusion model (Morphological Observation Neural Enhancement Tool, or MONET) on a large dataset to predict cell paint channels from brightfield images. We show that model quality improves with scale. The model uses a consistency architecture to generate time-lapse videos, despite the impossibility of obtaining cell paint video training data. In addition, we show that this architecture enables a form of in-context learning, allowing the model to partially transfer to out-of-distribution cell lines and imaging protocols. Virtual cell painting is not intended to replace physical cell painting completely, but to act as a complementary tool enabling novel workflows in biological research.

High-throughput screening techniques are commonly used to obtain large quantities of data in many fields of biology. It is well known that artifacts arising from variability in the technical execution of different experimental batches within such screens confound these observations and can lead to invalid biological conclusions. It is therefore necessary to account for these batch effects when analyzing outcomes. In this paper we describe RxRx1, a biological dataset designed specifically for the systematic study of batch effect correction methods. The dataset consists of 125,510 high-resolution fluorescence microscopy images of human cells under 1,138 genetic perturbations in 51 experimental batches across 4 cell types. Visual inspection of the images alone clearly demonstrates significant batch effects. We propose a classification task designed to evaluate the effectiveness of experimental batch correction methods on these images and examine the performance of a number of correction methods on this task. Our goal in releasing RxRx1 is to encourage the development of effective experimental batch correction methods that generalize well to unseen experimental batches. The dataset can be downloaded at https://rxrx.ai.

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding cell identity from the transcriptomic data, such as annotating cell types, has become an important task in bioinformatics. As these semantic aspects are determined by human experts, it is impossible for AI models to effectively carry out cell identity understanding tasks without the supervision signals provided by single-cell and label pairs. The single-cell pre-trained language models (PLMs) currently used for this task are trained only on a single modality, transcriptomics data, lack an understanding of cell identity knowledge. As a result, they have to be fine-tuned for downstream tasks and struggle when lacking labeled data with the desired semantic labels. To address this issue, we propose an innovative solution by constructing a unified representation of single-cell data and natural language during the pre-training phase, allowing the model to directly incorporate insights related to cell identity. More specifically, we introduce LangCell, the first Language-Cell pre-training framework. LangCell utilizes texts enriched with cell identity information to gain a profound comprehension of cross-modal knowledge. Results from experiments conducted on different benchmarks show that LangCell is the only single-cell PLM that can work effectively in zero-shot cell identity understanding scenarios, and also significantly outperforms existing models in few-shot and fine-tuning cell identity understanding scenarios.

Many LLM tasks are performed in large batches or even offline, and the performance indictor for which is throughput. These tasks usually show the characteristic of prefix sharing, where different prompt input can partially show the common prefix. However, the existing LLM inference engines tend to optimize the streaming requests and show limitations of supporting the large batched tasks with the prefix sharing characteristic. The existing solutions use the LRU-based cache to reuse the KV context of common prefix. The KV context that is about to be reused may prematurely be evicted with the implicit cache management. Even if not evicted, the lifetime of the shared KV context is extended since requests sharing the same context are not scheduled together, resulting in larger memory usage. These streaming oriented systems schedule the requests in the first-come-first-serve or similar order. As a result, the requests with larger ratio of decoding steps may be scheduled too late to be able to mix with the prefill chunks to increase the hardware utilization. Besides, the token and request number based batching can limit the size of token-batch, which keeps the GPU from saturating for the iterations dominated by decoding tokens. We propose BatchLLM to address the above problems. BatchLLM explicitly identifies the common prefixes globally. The requests sharing the same prefix will be scheduled together to reuse the KV context the best, which also shrinks the lifetime of common KV memory. BatchLLM reorders the requests and schedules the requests with larger ratio of decoding first to better mix the decoding tokens with the latter prefill chunks and applies memory-centric token batching to enlarge the token-batch sizes, which helps to increase the GPU utilization. Extensive evaluation shows that BatchLLM outperforms vLLM by 1.1x to 2x on a set of microbenchmarks and two typical industry workloads.

As large language models (LLMs) evolve to handle increasingly longer contexts, serving inference requests for context lengths in the range of millions of tokens presents unique challenges. While existing techniques are effective for training, they fail to address the unique challenges of inference, such as varying prefill and decode phases and their associated latency constraints - like Time to First Token (TTFT) and Time Between Tokens (TBT). Furthermore, there are no long context inference solutions that allow batching requests to increase the hardware utilization today. In this paper, we propose three key innovations for efficient interactive long context LLM inference, without resorting to any approximation: adaptive chunking to reduce prefill overheads in mixed batching, Sequence Pipeline Parallelism (SPP) to lower TTFT, and KV Cache Parallelism (KVP) to minimize TBT. These contributions are combined into a 3D parallelism strategy, enabling Mnemosyne to scale interactive inference to context lengths at least up to 10 million tokens with high throughput enabled with batching. To our knowledge, Mnemosyne is the first to be able to achieve support for 10 million long context inference efficiently, while satisfying production-grade SLOs on TBT (30ms) on contexts up to and including 10 million.

Predicting how cells respond to genetic perturbations is fundamental to understanding gene function, disease mechanisms, and therapeutic development. While recent deep learning approaches have shown promise in modeling single-cell perturbation responses, they struggle to generalize across cell types and perturbation contexts due to limited contextual information during generation. We introduce PT-RAG (Perturbation-aware Two-stage Retrieval-Augmented Generation), a novel framework that extends Retrieval-Augmented Generation beyond traditional language-model applications to cellular biology. Unlike standard RAG systems designed for text retrieval with pre-trained LLMs, perturbation retrieval lacks established similarity metrics and requires learning what constitutes relevant context, making differentiable retrieval essential. PT-RAG addresses this through a two-stage pipeline: first, retrieving candidate perturbations K using GenePT embeddings, then adaptively refining the selection through Gumbel-Softmax discrete sampling conditioned on both the cell state and the input perturbation. This cell-type-aware differentiable retrieval enables end-to-end optimization of the retrieval objective jointly with generation. On the Replogle-Nadig single-gene perturbation dataset, we demonstrate that PT-RAG outperforms both STATE and vanilla RAG under identical experimental conditions, with the strongest gains in distributional similarity metrics (W_1, W_2). Notably, vanilla RAG's dramatic failure is itself a key finding: it demonstrates that differentiable, cell-type-aware retrieval is essential in this domain, and that naive retrieval can actively harm performance. Our results establish retrieval-augmented generation as a promising paradigm for modelling cellular responses to gene perturbation. The code to reproduce our experiments is available at https://github.com/difra100/PT-RAG_ICLR.

Large language models excel at interpreting complex natural language instructions, enabling them to perform a wide range of tasks. In the life sciences, single-cell RNA sequencing (scRNA-seq) data serves as the "language of cellular biology", capturing intricate gene expression patterns at the single-cell level. However, interacting with this "language" through conventional tools is often inefficient and unintuitive, posing challenges for researchers. To address these limitations, we present InstructCell, a multi-modal AI copilot that leverages natural language as a medium for more direct and flexible single-cell analysis. We construct a comprehensive multi-modal instruction dataset that pairs text-based instructions with scRNA-seq profiles from diverse tissues and species. Building on this, we develop a multi-modal cell language architecture capable of simultaneously interpreting and processing both modalities. InstructCell empowers researchers to accomplish critical tasks-such as cell type annotation, conditional pseudo-cell generation, and drug sensitivity prediction-using straightforward natural language commands. Extensive evaluations demonstrate that InstructCell consistently meets or exceeds the performance of existing single-cell foundation models, while adapting to diverse experimental conditions. More importantly, InstructCell provides an accessible and intuitive tool for exploring complex single-cell data, lowering technical barriers and enabling deeper biological insights.

Single-cell RNA sequencing (scRNA-seq) data are often confounded by technical or biological batch effects. Existing deep learning models mitigate these effects but often discard batch-specific information, potentially losing valuable biological insights. We propose a Mixed Effects Deep Learning (MEDL) autoencoder framework that separately models batch-invariant (fixed effects) and batch-specific (random effects) components. By decoupling batch-invariant biological states from batch variations, our framework integrates both into predictive models. Our approach also generates 2D visualizations of how the same cell appears across batches, enhancing interpretability. Retaining both fixed and random effect latent spaces improves classification accuracy. We applied our framework to three datasets spanning the cardiovascular system (Healthy Heart), Autism Spectrum Disorder (ASD), and Acute Myeloid Leukemia (AML). With 147 batches in the Healthy Heart dataset, far exceeding typical numbers, we tested our framework's ability to handle many batches. In the ASD dataset, our approach captured donor heterogeneity between autistic and healthy individuals. In the AML dataset, it distinguished donor heterogeneity despite missing cell types and diseased donors exhibiting both healthy and malignant cells. These results highlight our framework's ability to characterize fixed and random effects, enhance batch effect visualization, and improve prediction accuracy across diverse datasets.

This paper presents MoE-Gen, a high-throughput MoE inference system optimized for single-GPU execution. Existing inference systems rely on model-based or continuous batching strategies, originally designed for interactive inference, which result in excessively small batches for MoE's key modules-attention and expert modules-leading to poor throughput. To address this, we introduce module-based batching, which accumulates tokens in host memory and dynamically launches large batches on GPUs to maximize utilization. Additionally, we optimize the choice of batch sizes for each module in an MoE to fully overlap GPU computation and communication, maximizing throughput. Evaluation demonstrates that MoE-Gen achieves 8-31x higher throughput compared to state-of-the-art systems employing model-based batching (FlexGen, MoE-Lightning, DeepSpeed), and offers even greater throughput improvements over continuous batching systems (e.g., vLLM and Ollama) on popular MoE models (DeepSeek and Mixtral) across offline inference tasks. MoE-Gen's source code is publicly available at https://github.com/EfficientMoE/MoE-Gen

Large language models (LLMs) and emerging agentic frameworks are beginning to transform single-cell biology by enabling natural-language reasoning, generative annotation, and multimodal data integration. However, progress remains fragmented across data modalities, architectures, and evaluation standards. LLM4Cell presents the first unified survey of 58 foundation and agentic models developed for single-cell research, spanning RNA, ATAC, multi-omic, and spatial modalities. We categorize these methods into five families-foundation, text-bridge, spatial, multimodal, epigenomic, and agentic-and map them to eight key analytical tasks including annotation, trajectory and perturbation modeling, and drug-response prediction. Drawing on over 40 public datasets, we analyze benchmark suitability, data diversity, and ethical or scalability constraints, and evaluate models across 10 domain dimensions covering biological grounding, multi-omics alignment, fairness, privacy, and explainability. By linking datasets, models, and evaluation domains, LLM4Cell provides the first integrated view of language-driven single-cell intelligence and outlines open challenges in interpretability, standardization, and trustworthy model development.

Many methods have been proposed for removing batch effects and aligning single-cell RNA (scRNA) datasets. However, performance is typically evaluated based on multiple parameters and few datasets, creating challenges in assessing which method is best for aligning data at scale. Here, we introduce the K-Neighbors Intersection (KNI) score, a single score that both penalizes batch effects and measures accuracy at cross-dataset cell-type label prediction alongside carefully curated small (scMARK) and large (scREF) benchmarks comprising 11 and 46 human scRNA studies respectively, where we have standardized author labels. Using the KNI score, we evaluate and optimize approaches for cross-dataset single-cell RNA integration. We introduce Batch Adversarial single-cell Variational Inference (BA-scVI), as a new variant of scVI that uses adversarial training to penalize batch-effects in the encoder and decoder, and show this approach outperforms other methods. In the resulting aligned space, we find that the granularity of cell-type groupings is conserved, supporting the notion that whole-organism cell-type maps can be created by a single model without loss of information.

Prompting and in-context learning (ICL) have become efficient learning paradigms for large language models (LLMs). However, LLMs suffer from prompt brittleness and various bias factors in the prompt, including but not limited to the formatting, the choice verbalizers, and the ICL examples. To address this problem that results in unexpected performance degradation, calibration methods have been developed to mitigate the effects of these biases while recovering LLM performance. In this work, we first conduct a systematic analysis of the existing calibration methods, where we both provide a unified view and reveal the failure cases. Inspired by these analyses, we propose Batch Calibration (BC), a simple yet intuitive method that controls the contextual bias from the batched input, unifies various prior approaches, and effectively addresses the aforementioned issues. BC is zero-shot, inference-only, and incurs negligible additional costs. In the few-shot setup, we further extend BC to allow it to learn the contextual bias from labeled data. We validate the effectiveness of BC with PaLM 2-(S, M, L) and CLIP models and demonstrate state-of-the-art performance over previous calibration baselines across more than 10 natural language understanding and image classification tasks.

Context-augmented generation (CAG) techniques, including RAG and ICL, require the efficient combination of multiple contexts to generate responses to user queries. Directly inputting these contexts as a sequence introduces a considerable computational burden by re-encoding the combined selection of contexts for every request. To address this, we explore the promising potential of parallel encoding to independently pre-compute and cache each context's KV states. This approach enables the direct loading of cached states during inference while accommodating more contexts through position reuse across contexts. However, due to misalignments in attention distribution, directly applying parallel encoding results in a significant performance drop. To enable effective and efficient CAG, we propose Adaptive Parallel Encoding (APE), which brings shared prefix, attention temperature, and scaling factor to align the distribution of parallel encoding with sequential encoding. Results on RAG and ICL tasks demonstrate that APE can preserve 98% and 93% sequential encoding performance using the same inputs while outperforming parallel encoding by 3.6% and 7.9%, respectively. It also scales to many-shot CAG, effectively encoding hundreds of contexts in parallel. Efficiency evaluation shows that APE can achieve an end-to-end 4.5times speedup by reducing 28times prefilling time for a 128K-length context.

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects -- a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15.github.io/CellFlux/.

Large language models (LLMs) with extended context windows have become increasingly prevalent for tackling complex tasks. However, the substantial Key-Value (KV) cache required for long-context LLMs poses significant deployment challenges. Existing approaches either discard potentially critical information needed for future generations or offer limited efficiency gains due to high computational overhead. In this paper, we introduce Chelsea, a simple yet effective framework for online KV cache clustering. Our approach is based on the observation that key states exhibit high similarity along the sequence dimension. To enable efficient clustering, we divide the sequence into chunks and propose Chunked Soft Matching, which employs an alternating partition strategy within each chunk and identifies clusters based on similarity. Chelsea then merges the KV cache within each cluster into a single centroid. Additionally, we provide a theoretical analysis of the computational complexity and the optimality of the intra-chunk partitioning strategy. Extensive experiments across various models and long-context benchmarks demonstrate that Chelsea achieves up to 80% reduction in KV cache memory usage while maintaining comparable model performance. Moreover, with minimal computational overhead, Chelsea accelerates the decoding stage of inference by up to 3.19times and reduces end-to-end latency by up to 2.72times.

Modeling cellular states and predicting their responses to perturbations are central challenges in computational biology and the development of virtual cells. Existing foundation models for single-cell transcriptomics provide powerful static representations, but they do not explicitly model the distribution of cellular states for generative simulation. Here, we introduce Lingshu-Cell, a masked discrete diffusion model that learns transcriptomic state distributions and supports conditional simulation under perturbation. By operating directly in a discrete token space that is compatible with the sparse, non-sequential nature of single-cell transcriptomic data, Lingshu-Cell captures complex transcriptome-wide expression dependencies across approximately 18,000 genes without relying on prior gene selection, such as filtering by high variability or ranking by expression level. Across diverse tissues and species, Lingshu-Cell accurately reproduces transcriptomic distributions, marker-gene expression patterns and cell-subtype proportions, demonstrating its ability to capture complex cellular heterogeneity. Moreover, by jointly embedding cell type or donor identity with perturbation, Lingshu-Cell can predict whole-transcriptome expression changes for novel combinations of identity and perturbation. It achieves leading performance on the Virtual Cell Challenge H1 genetic perturbation benchmark and in predicting cytokine-induced responses in human PBMCs. Together, these results establish Lingshu-Cell as a flexible cellular world model for in silico simulation of cell states and perturbation responses, laying the foundation for a new paradigm in biological discovery and perturbation screening.

Recent advances with large language models (LLM) illustrate their diverse capabilities. We propose a novel algorithm, staged speculative decoding, to accelerate LLM inference in small-batch, on-device scenarios. We address the low arithmetic intensity of small-batch inference by improving upon previous work in speculative decoding. First, we restructure the speculative batch as a tree, which reduces generation costs and increases the expected tokens per batch. Second, we add a second stage of speculative decoding. Taken together, we reduce single-batch decoding latency by 3.16x with a 762M parameter GPT-2-L model while perfectly preserving output quality.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

Offline batch inference, which leverages the flexibility of request batching to achieve higher throughput and lower costs, is becoming more popular for latency-insensitive applications. Meanwhile, recent progress in model capability and modality makes requests more diverse in compute and memory demands, creating unique opportunities for throughput improvement by resource overlapping. However, a request schedule that maximizes resource overlapping can conflict with the schedule that maximizes prefix sharing, a widely-used performance optimization, causing sub-optimal inference throughput. We present BlendServe, a system that maximizes resource utilization of offline batch inference by combining the benefits of resource overlapping and prefix sharing using a resource-aware prefix tree. BlendServe exploits the relaxed latency requirements in offline batch inference to reorder and overlap requests with varied resource demands while ensuring high prefix sharing. We evaluate BlendServe on a variety of synthetic multi-modal workloads and show that it provides up to 1.44times throughput boost compared to widely-used industry standards, vLLM and SGLang.

Instance segmentation is critical in biomedical imaging to accurately distinguish individual objects like cells, which often overlap and vary in size. Recent query-based methods, where object queries guide segmentation, have shown strong performance. While U-Net has been a go-to architecture in medical image segmentation, its potential in query-based approaches remains largely unexplored. In this work, we present IAUNet, a novel query-based U-Net architecture. The core design features a full U-Net architecture, enhanced by a novel lightweight convolutional Pixel decoder, making the model more efficient and reducing the number of parameters. Additionally, we propose a Transformer decoder that refines object-specific features across multiple scales. Finally, we introduce the 2025 Revvity Full Cell Segmentation Dataset, a unique resource with detailed annotations of overlapping cell cytoplasm in brightfield images, setting a new benchmark for biomedical instance segmentation. Experiments on multiple public datasets and our own show that IAUNet outperforms most state-of-the-art fully convolutional, transformer-based, and query-based models and cell segmentation-specific models, setting a strong baseline for cell instance segmentation tasks. Code is available at https://github.com/SlavkoPrytula/IAUNet

High-throughput screening techniques, such as microscopy imaging of cellular responses to genetic and chemical perturbations, play a crucial role in drug discovery and biomedical research. However, robust perturbation screening for de novo cell lines remains challenging due to the significant morphological and biological heterogeneity across cell lines. To address this, we propose a novel framework that integrates external biological knowledge into existing pretraining strategies to enhance microscopy image profiling models. Our approach explicitly disentangles perturbation-specific and cell line-specific representations using external biological information. Specifically, we construct a knowledge graph leveraging protein interaction data from STRING and Hetionet databases to guide models toward perturbation-specific features during pretraining. Additionally, we incorporate transcriptomic features from single-cell foundation models to capture cell line-specific representations. By learning these disentangled features, our method improves the generalization of imaging models to de novo cell lines. We evaluate our framework on the RxRx database through one-shot fine-tuning on an RxRx1 cell line and few-shot fine-tuning on cell lines from the RxRx19a dataset. Experimental results demonstrate that our method enhances microscopy image profiling for de novo cell lines, highlighting its effectiveness in real-world phenotype-based drug discovery applications.

As Large Language Models (LLMs) rapidly evolve, their influence in science is becoming increasingly prominent. The emerging capabilities of LLMs in task generalization and free-form dialogue can significantly advance fields like chemistry and biology. However, the field of single-cell biology, which forms the foundational building blocks of living organisms, still faces several challenges. High knowledge barriers and limited scalability in current methods restrict the full exploitation of LLMs in mastering single-cell data, impeding direct accessibility and rapid iteration. To this end, we introduce ChatCell, which signifies a paradigm shift by facilitating single-cell analysis with natural language. Leveraging vocabulary adaptation and unified sequence generation, ChatCell has acquired profound expertise in single-cell biology and the capability to accommodate a diverse range of analysis tasks. Extensive experiments further demonstrate ChatCell's robust performance and potential to deepen single-cell insights, paving the way for more accessible and intuitive exploration in this pivotal field. Our project homepage is available at https://zjunlp.github.io/project/ChatCell.

Recent large language model applications, such as Retrieval-Augmented Generation and chatbots, have led to an increased need to process longer input contexts. However, this requirement is hampered by inherent limitations. Architecturally, models are constrained by a context window defined during training. Additionally, processing extensive texts requires substantial GPU memory. We propose a novel approach, Finch, to compress the input context by leveraging the pre-trained model weights of the self-attention. Given a prompt and a long text, Finch iteratively identifies the most relevant Key (K) and Value (V) pairs over chunks of the text conditioned on the prompt. Only such pairs are stored in the KV cache, which, within the space constrained by the context window, ultimately contains a compressed version of the long text. Our proposal enables models to consume large inputs even with high compression (up to 93x) while preserving semantic integrity without the need for fine-tuning.

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

The Non-Local Network (NLNet) presents a pioneering approach for capturing long-range dependencies, via aggregating query-specific global context to each query position. However, through a rigorous empirical analysis, we have found that the global contexts modeled by non-local network are almost the same for different query positions within an image. In this paper, we take advantage of this finding to create a simplified network based on a query-independent formulation, which maintains the accuracy of NLNet but with significantly less computation. We further observe that this simplified design shares similar structure with Squeeze-Excitation Network (SENet). Hence we unify them into a three-step general framework for global context modeling. Within the general framework, we design a better instantiation, called the global context (GC) block, which is lightweight and can effectively model the global context. The lightweight property allows us to apply it for multiple layers in a backbone network to construct a global context network (GCNet), which generally outperforms both simplified NLNet and SENet on major benchmarks for various recognition tasks. The code and configurations are released at https://github.com/xvjiarui/GCNet.

Diffusion Language Models (DLMs) have recently achieved significant success due to their any-order generation capabilities. However, existing inference methods typically rely on local, immediate-step metrics such as confidence or entropy which inherently lack a more reliable perspective. This limitation frequently leads to inconsistent sampling trajectories and suboptimal generation quality. To address this, we propose Coherent Contextual Decoding (CCD), a novel inference framework built upon two core innovations. First, CCD employs a trajectory rectification mechanism that leverages historical context to enhance sequence coherence, enabling the early rejection of suboptimal paths. We demonstrate that this mechanism is theoretically equivalent to modeling the consistency of historical steps via the conditional mutual information between context and token predictions. Building on this theoretical insight, we further address the inefficiency of conventional uniform decoding budgets. Instead of rigid allocations based on diffusion steps, we introduce an adaptive sampling strategy that dynamically adjusts the unmasking budget for each step according to our consistency metric. Consequently, our method significantly improves the quality of generation trajectories while accelerating the sampling process. Empirically, our method achieves a simultaneous enhancement in both inference speed and performance across diverse benchmarks on Dream and LLaDA, delivering up to 3.48x speedup alongside 3.91% performance improvement.

Long-context LLMs demand accurate inference at low latency, yet decoding becomes primarily constrained by KV cache as context grows. Prior pruning methods are largely context-agnostic: their token selection ignores step-wise relevance and local semantics, which undermines quality. Moreover, their irregular accesses and selection overheads yield only limited wall-clock speedups. To address this, we propose CHESS, an algorithm-system co-design KV-cache management system. Algorithmically, CHESS introduces a context-aware, hierarchical selection policy that dynamically reconstructs a coherent context for the current decoding. System-wise, coarse granularity selection eliminates expensive data movement, fully realizing practical acceleration from theoretical sparsity. Extensive evaluations demonstrate that CHESS surpasses Full-KV quality using only 1\% of the KV cache, delivers low-latency stable inference with up to 4.56times higher throughput, and consistently outperforms other strong baselines. Code is available at https://anonymous.4open.science/r/CHESS-9958/{https://anonymous.4open.science/r/CHESS/}.

Understanding context is key to understanding human language, an ability which Large Language Models (LLMs) have been increasingly seen to demonstrate to an impressive extent. However, though the evaluation of LLMs encompasses various domains within the realm of Natural Language Processing, limited attention has been paid to probing their linguistic capability of understanding contextual features. This paper introduces a context understanding benchmark by adapting existing datasets to suit the evaluation of generative models. This benchmark comprises of four distinct tasks and nine datasets, all featuring prompts designed to assess the models' ability to understand context. First, we evaluate the performance of LLMs under the in-context learning pretraining scenario. Experimental results indicate that pre-trained dense models struggle with understanding more nuanced contextual features when compared to state-of-the-art fine-tuned models. Second, as LLM compression holds growing significance in both research and real-world applications, we assess the context understanding of quantized models under in-context-learning settings. We find that 3-bit post-training quantization leads to varying degrees of performance reduction on our benchmark. We conduct an extensive analysis of these scenarios to substantiate our experimental results.

Spatial transcriptomics enables simultaneous measurement of gene expression and tissue morphology, offering unprecedented insights into cellular organization and disease mechanisms. However, the field lacks comprehensive benchmarks for evaluating multimodal learning methods that leverage both histology images and gene expression data. Here, we present HESCAPE, a large-scale benchmark for cross-modal contrastive pretraining in spatial transcriptomics, built on a curated pan-organ dataset spanning 6 different gene panels and 54 donors. We systematically evaluated state-of-the-art image and gene expression encoders across multiple pretraining strategies and assessed their effectiveness on two downstream tasks: gene mutation classification and gene expression prediction. Our benchmark demonstrates that gene expression encoders are the primary determinant of strong representational alignment, and that gene models pretrained on spatial transcriptomics data outperform both those trained without spatial data and simple baseline approaches. However, downstream task evaluation reveals a striking contradiction: while contrastive pretraining consistently improves gene mutation classification performance, it degrades direct gene expression prediction compared to baseline encoders trained without cross-modal objectives. We identify batch effects as a key factor that interferes with effective cross-modal alignment. Our findings highlight the critical need for batch-robust multimodal learning approaches in spatial transcriptomics. To accelerate progress in this direction, we release HESCAPE, providing standardized datasets, evaluation protocols, and benchmarking tools for the community

As large language models increasingly gain popularity in real-world applications, processing extremely long contexts, often exceeding the model's pre-trained context limits, has emerged as a critical challenge. While existing approaches to efficient long-context processing show promise, recurrent compression-based methods struggle with information preservation, whereas random access approaches require substantial memory resources. We introduce REFORM, a novel inference framework that efficiently handles long contexts through a two-phase approach. First, it incrementally processes input chunks while maintaining a compressed KV cache, constructs cross-layer context embeddings, and utilizes early exit strategy for improved efficiency. Second, it identifies and gathers essential tokens via similarity matching and selectively recomputes the KV cache. Compared to baselines, REFORM achieves over 50% and 27% performance gains on RULER and BABILong respectively at 1M context length. It also outperforms baselines on Infinite-Bench and MM-NIAH, demonstrating flexibility across diverse tasks and domains. Additionally, REFORM reduces inference time by 30% and peak memory usage by 5%, achieving both efficiency and superior performance.

Performing inference on hundreds of thousands of samples with large language models (LLMs) can be computationally and financially costly. We propose batch prompting, a simple alternative prompting approach that enables the LLM to run inference in batches, instead of one sample at a time. Our method reduces both token and time costs while retaining downstream performance. We theoretically demonstrate that under a few-shot in-context learning setting, the inference costs decrease almost inverse linearly with the number of samples in each batch. We extensively validate the effectiveness of batch prompting on ten datasets across commonsense QA, arithmetic reasoning, and NLI/NLU: batch prompting significantly~(up to 5times with six samples in batch) reduces the LLM (Codex) inference token and time costs while achieving better or comparable performance. Our analysis shows that the number of samples in each batch and the complexity of tasks affect its performance. Further, batch prompting can be applied across different LLMs and reasoning methods.

Providing Large Language Models with relevant contextual knowledge at inference time has been shown to greatly improve the quality of their generations. This is often achieved by prepending informative passages of text, or 'contexts', retrieved from external knowledge bases to their input. However, processing additional contexts online incurs significant computation costs that scale with their length. State Space Models (SSMs) offer a promising solution by allowing a database of contexts to be mapped onto fixed-dimensional states from which to start the generation. A key challenge arises when attempting to leverage information present across multiple contexts, since there is no straightforward way to condition generation on multiple independent states in existing SSMs. To address this, we leverage a simple mathematical relation derived from SSM dynamics to compose multiple states into one that efficiently approximates the effect of concatenating raw context tokens. Since the temporal ordering of contexts can often be uninformative, we enforce permutation-invariance by efficiently averaging states obtained via our composition algorithm across all possible context orderings. We evaluate our resulting method on WikiText and MSMARCO in both zero-shot and fine-tuned settings, and show that we can match the strongest performing baseline while enjoying on average 5.4x speedup.

There is large consent that successful training of deep networks requires many thousand annotated training samples. In this paper, we present a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently. The architecture consists of a contracting path to capture context and a symmetric expanding path that enables precise localization. We show that such a network can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks. Using the same network trained on transmitted light microscopy images (phase contrast and DIC) we won the ISBI cell tracking challenge 2015 in these categories by a large margin. Moreover, the network is fast. Segmentation of a 512x512 image takes less than a second on a recent GPU. The full implementation (based on Caffe) and the trained networks are available at http://lmb.informatik.uni-freiburg.de/people/ronneber/u-net .

We introduce Latent Meaning Cells, a deep latent variable model which learns contextualized representations of words by combining local lexical context and metadata. Metadata can refer to granular context, such as section type, or to more global context, such as unique document ids. Reliance on metadata for contextualized representation learning is apropos in the clinical domain where text is semi-structured and expresses high variation in topics. We evaluate the LMC model on the task of zero-shot clinical acronym expansion across three datasets. The LMC significantly outperforms a diverse set of baselines at a fraction of the pre-training cost and learns clinically coherent representations. We demonstrate that not only is metadata itself very helpful for the task, but that the LMC inference algorithm provides an additional large benefit.

Quantifying cell morphology using images and machine learning has proven to be a powerful tool to study the response of cells to treatments. However, models used to quantify cellular morphology are typically trained with a single microscopy imaging type. This results in specialized models that cannot be reused across biological studies because the technical specifications do not match (e.g., different number of channels), or because the target experimental conditions are out of distribution. Here, we present CHAMMI-75, an open access dataset of heterogeneous, multi-channel microscopy images from 75 diverse biological studies. We curated this resource from publicly available sources to investigate cellular morphology models that are channel-adaptive and can process any microscopy image type. Our experiments show that training with CHAMMI-75 can improve performance in multi-channel bioimaging tasks primarily because of its high diversity in microscopy modalities. This work paves the way to create the next generation of cellular morphology models for biological studies.

Accelerating large language model (LLM) inference is critical for real-world deployments requiring high throughput and low latency. Contextual sparsity, where each token dynamically activates only a small subset of the model parameters, shows promise but does not scale to large batch sizes due to union of active neurons quickly approaching dense computation. We introduce Polar Sparsity, highlighting a key shift in sparsity importance from MLP to Attention layers as we scale batch size and sequence length. While MLP layers become more compute-efficient under batching, their sparsity vanishes. In contrast, attention becomes increasingly more expensive at scale, while their head sparsity remains stable and batch-invariant. We develop hardware-efficient, sparsity-aware GPU kernels for selective MLP and Attention computations, delivering up to \(2.2\times\) end-to-end speedups for models like OPT, LLaMA-2 \& 3, across various batch sizes and sequence lengths without compromising accuracy. To our knowledge, this is the first work to demonstrate that contextual sparsity can scale effectively to large batch sizes, delivering substantial inference acceleration with minimal changes, making Polar Sparsity practical for large-scale, high-throughput LLM deployment systems. Our code is available at: https://github.com/susavlsh10/Polar-Sparsity.

Extracting single-cell information from microscopy data requires accurate instance-wise segmentations. Obtaining pixel-wise segmentations from microscopy imagery remains a challenging task, especially with the added complexity of microstructured environments. This paper presents a novel dataset for segmenting yeast cells in microstructures. We offer pixel-wise instance segmentation labels for both cells and trap microstructures. In total, we release 493 densely annotated microscopy images. To facilitate a unified comparison between novel segmentation algorithms, we propose a standardized evaluation strategy for our dataset. The aim of the dataset and evaluation strategy is to facilitate the development of new cell segmentation approaches. The dataset is publicly available at https://christophreich1996.github.io/yeast_in_microstructures_dataset/ .

Scaling language models to long contexts is often bottlenecked by the size of the key-value (KV) cache. In deployed settings, long contexts are typically managed through compaction in token space via summarization. However, summarization can be highly lossy, substantially harming downstream performance. Recent work on Cartridges has shown that it is possible to train highly compact KV caches in latent space that closely match full-context performance, but at the cost of slow and expensive end-to-end optimization. This work describes an approach for fast context compaction in latent space through Attention Matching, which constructs compact keys and values to reproduce attention outputs and preserve attention mass at a per-KV-head level. We show that this formulation naturally decomposes into simple subproblems, some of which admit efficient closed-form solutions. Within this framework, we develop a family of methods that significantly push the Pareto frontier of compaction time versus quality, achieving up to 50x compaction in seconds on some datasets with little quality loss.

Attention mechanisms have revolutionized sequence learning but suffer from quadratic computational complexity. This paper introduces Lattice, a novel recurrent neural network (RNN) mechanism that leverages the inherent low-rank structure of K-V matrices to efficiently compress the cache into a fixed number of memory slots, achieving sub-quadratic complexity. We formulate this compression as an online optimization problem and derive a dynamic memory update rule based on a single gradient descent step. The resulting recurrence features a state- and input-dependent gating mechanism, offering an interpretable memory update process. The core innovation is the orthogonal update: each memory slot is updated exclusively with information orthogonal to its current state hence incorporation of only novel, non-redundant data, which minimizes the interference with previously stored information. The experimental results show that Lattice achieves the best perplexity compared to all baselines across diverse context lengths, with performance improvement becoming more pronounced as the context length increases.

Instance segmentation of neurons in volumetric light microscopy images of nervous systems enables groundbreaking research in neuroscience by facilitating joint functional and morphological analyses of neural circuits at cellular resolution. Yet said multi-neuron light microscopy data exhibits extremely challenging properties for the task of instance segmentation: Individual neurons have long-ranging, thin filamentous and widely branching morphologies, multiple neurons are tightly inter-weaved, and partial volume effects, uneven illumination and noise inherent to light microscopy severely impede local disentangling as well as long-range tracing of individual neurons. These properties reflect a current key challenge in machine learning research, namely to effectively capture long-range dependencies in the data. While respective methodological research is buzzing, to date methods are typically benchmarked on synthetic datasets. To address this gap, we release the FlyLight Instance Segmentation Benchmark (FISBe) dataset, the first publicly available multi-neuron light microscopy dataset with pixel-wise annotations. In addition, we define a set of instance segmentation metrics for benchmarking that we designed to be meaningful with regard to downstream analyses. Lastly, we provide three baselines to kick off a competition that we envision to both advance the field of machine learning regarding methodology for capturing long-range data dependencies, and facilitate scientific discovery in basic neuroscience.

Recurrent Neural Network (RNN) inference exhibits low hardware utilization due to the strict data dependencies across time-steps. Batching multiple requests can increase throughput. However, RNN batching requires a large amount of padding since the batched input sequences may largely differ in length. Schemes that dynamically update the batch every few time-steps avoid padding. However, they require executing different RNN layers in a short timespan, decreasing energy efficiency. Hence, we propose E-BATCH, a low-latency and energy-efficient batching scheme tailored to RNN accelerators. It consists of a runtime system and effective hardware support. The runtime concatenates multiple sequences to create large batches, resulting in substantial energy savings. Furthermore, the accelerator notifies it when the evaluation of a sequence is done, so that a new sequence can be immediately added to a batch, thus largely reducing the amount of padding. E-BATCH dynamically controls the number of time-steps evaluated per batch to achieve the best trade-off between latency and energy efficiency for the given hardware platform. We evaluate E-BATCH on top of E-PUR and TPU. In E-PUR, E-BATCH improves throughput by 1.8x and energy-efficiency by 3.6x, whereas in TPU, it improves throughput by 2.1x and energy-efficiency by 1.6x, over the state-of-the-art.

The exploration and application of Large Language Models (LLMs) is thriving. To reduce deployment costs, continuous batching has become an essential feature in current service frameworks. The effectiveness of continuous batching relies on an accurate estimate of the memory requirements of requests. However, due to the diversity in request output lengths, existing frameworks tend to adopt aggressive or conservative schedulers, which often result in significant overestimation or underestimation of memory consumption. Consequently, they suffer from harmful request evictions or prolonged queuing times, failing to achieve satisfactory throughput under strict Service Level Agreement (SLA) guarantees (a.k.a. goodput), across various LLM application scenarios with differing input-output length distributions. To address this issue, we propose a novel Past-Future scheduler that precisely estimates the peak memory resources required by the running batch via considering the historical distribution of request output lengths and calculating memory occupancy at each future time point. It adapts to applications with all types of input-output length distributions, balancing the trade-off between request queuing and harmful evictions, thereby consistently achieving better goodput. Furthermore, to validate the effectiveness of the proposed scheduler, we developed a high-performance LLM serving framework, LightLLM, that implements the Past-Future scheduler. Compared to existing aggressive or conservative schedulers, LightLLM demonstrates superior goodput, achieving up to 2-3times higher goodput than other schedulers under heavy loads. LightLLM is open source to boost the research in such direction (https://github.com/ModelTC/lightllm).

Large language models are often used to answer queries grounded in large text corpora (e.g. codebases, legal documents, or chat histories) by placing the entire corpus in the context window and leveraging in-context learning (ICL). Although current models support contexts of 100K-1M tokens, this setup is costly to serve because the memory consumption of the KV cache scales with input length. We explore an alternative: training a smaller KV cache offline on each corpus. At inference time, we load this trained KV cache, which we call a Cartridge, and decode a response. Critically, the cost of training a Cartridge can be amortized across all the queries referencing the same corpus. However, we find that the naive approach of training the Cartridge with next-token prediction on the corpus is not competitive with ICL. Instead, we propose self-study, a training recipe in which we generate synthetic conversations about the corpus and train the Cartridge with a context-distillation objective. We find that Cartridges trained with self-study replicate the functionality of ICL, while being significantly cheaper to serve. On challenging long-context benchmarks, Cartridges trained with self-study match ICL performance while using 38.6x less memory and enabling 26.4x higher throughput. Self-study also extends the model's effective context length (e.g. from 128k to 484k tokens on MTOB) and surprisingly, leads to Cartridges that can be composed at inference time without retraining.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyperparameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods, but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Scaling long-context ability is essential for Large Language Models (LLMs). To amortize the memory consumption across multiple devices in long-context training, inter-data partitioning (a.k.a. Data Parallelism) and intra-data partitioning (a.k.a. Context Parallelism) are commonly used. Current training frameworks predominantly treat the two techniques as orthogonal, and establish static communication groups to organize the devices as a static mesh (e.g., a 2D mesh). However, the sequences for LLM training typically vary in lengths, no matter for texts, multi-modalities or reinforcement learning. The mismatch between data heterogeneity and static mesh causes redundant communication and imbalanced computation, degrading the training efficiency. In this work, we introduce ByteScale, an efficient, flexible, and scalable LLM training framework for large-scale mixed training of long and short sequences. The core of ByteScale is a novel parallelism strategy, namely Hybrid Data Parallelism (HDP), which unifies the inter- and intra-data partitioning with a dynamic mesh design. In particular, we build a communication optimizer, which eliminates the redundant communication for short sequences by data-aware sharding and dynamic communication, and further compresses the communication cost for long sequences by selective offloading. Besides, we also develop a balance scheduler to mitigate the imbalanced computation by parallelism-aware data assignment. We evaluate ByteScale with the model sizes ranging from 7B to 141B, context lengths from 256K to 2048K, on a production cluster with more than 12,000 GPUs. Experiment results show that ByteScale outperforms the state-of-the-art training system by up to 7.89x.

Single-cell RNA sequencing (scRNA-seq) enables high-resolution analysis of cellular heterogeneity, but its complexity, which is marked by high dimensionality, sparsity, and batch effects, which poses major computational challenges. Transformer-based models have made significant advances in this domain but are often limited by their quadratic complexity and suboptimal handling of long-range dependencies. In this work, we introduce GeneMamba, a scalable and efficient foundation model for single-cell transcriptomics built on state space modeling. Leveraging the Bi-Mamba architecture, GeneMamba captures bidirectional gene context with linear-time complexity, offering substantial computational gains over transformer baselines. The model is pretrained on nearly 30 million cells and incorporates biologically informed objectives, including pathway-aware contrastive loss and rank-based gene encoding. We evaluate GeneMamba across diverse tasks, including multi-batch integration, cell type annotation, and gene-gene correlation, demonstrating strong performance, interpretability, and robustness. These results position GeneMamba as a practical and powerful alternative to transformer-based methods, advancing the development of biologically grounded, scalable tools for large-scale single-cell data analysis.

Soft context compression reduces the computational workload of processing long contexts in LLMs by encoding long context into a smaller number of latent tokens. However, existing frameworks apply uniform compression ratios, failing to account for the extreme variance in natural language information density. While adopting a density-aware dynamic compression ratio seems intuitive, empirical investigations reveal that models struggle intrinsically with operations parameterized by input dependent, continuous structural hyperparameters. To resolve this pitfall, we introduce Semi-Dynamic Context Compression framework. Our approach features a Discrete Ratio Selector, which predicts a compression target based on intrinsic information density and quantizes it to a predefined set of discrete compression ratios. It is efficiently jointly trained with the compressor on synthetic data, with the summary lengths as a proxy to create labels for compression ratio prediction. Extensive evaluations confirm that our density-aware framework, utilizing mean pooling as the backbone, consistently outperforms static baselines, establishing a robust Pareto frontier for context compression techniques. Our code, data and model weights are available at https://github.com/yuyijiong/semi-dynamic-context-compress

Large language models have shown remarkable performance across a wide range of language tasks, owing to their exceptional capabilities in context modeling. The most commonly used method of context modeling is full self-attention, as seen in standard decoder-only Transformers. Although powerful, this method can be inefficient for long sequences and may overlook inherent input structures. To address these problems, an alternative approach is parallel context encoding, which splits the context into sub-pieces and encodes them parallelly. Because parallel patterns are not encountered during training, naively applying parallel encoding leads to performance degradation. However, the underlying reasons and potential mitigations are unclear. In this work, we provide a detailed analysis of this issue and identify that unusually high attention entropy can be a key factor. Furthermore, we adopt two straightforward methods to reduce attention entropy by incorporating attention sinks and selective mechanisms. Experiments on various tasks reveal that these methods effectively lower irregular attention entropy and narrow performance gaps. We hope this study can illuminate ways to enhance context modeling mechanisms.

Cell instance segmentation in fluorescence microscopy images is becoming essential for cancer dynamics and prognosis. Data extracted from cancer dynamics allows to understand and accurately model different metabolic processes such as proliferation. This enables customized and more precise cancer treatments. However, accurate cell instance segmentation, necessary for further cell tracking and behavior analysis, is still challenging in scenarios with high cell concentration and overlapping edges. Within this framework, we propose a novel cell instance segmentation approach based on the well-known U-Net architecture. To enforce the learning of morphological information per pixel, a deep distance transformer (DDT) acts as a back-bone model. The DDT output is subsequently used to train a top-model. The following top-models are considered: a three-class (e.g., foreground, background and cell border) U-net, and a watershed transform. The obtained results suggest a performance boost over traditional U-Net architectures. This opens an interesting research line around the idea of injecting morphological information into a fully convolutional model.

Despite the advancements and impressive performance of Multimodal Large Language Models (MLLMs) on benchmarks, their effectiveness in real-world, long-context, and multi-image tasks is unclear due to the benchmarks' limited scope. Existing benchmarks often focus on single-image and short-text samples, and when assessing multi-image tasks, they either limit the image count or focus on specific task (e.g time-series captioning), potentially obscuring the performance challenges of MLLMs. To address these limitations, we introduce MileBench, a pioneering benchmark designed to test the MultImodal Long-contExt capabilities of MLLMs. This benchmark comprises not only multimodal long contexts, but also multiple tasks requiring both comprehension and generation. We establish two distinct evaluation sets, diagnostic and realistic, to systematically assess MLLMs' long-context adaptation capacity and their ability to complete tasks in long-context scenarios. Our experimental results, obtained from testing 20 models, revealed that while the closed-source GPT-4(Vision) and Gemini 1.5 outperform others, most open-source MLLMs struggle in long-context situations. Interestingly, the performance gap tends to widen with an increase in the number of images. We strongly encourage an intensification of research efforts towards enhancing MLLMs' long-context capabilities, especially in scenarios involving multiple images.

This paper revisits the implementation of Load-balancing Loss (LBL) when training Mixture-of-Experts (MoEs) models. Specifically, LBL for MoEs is defined as N_E sum_{i=1}^{N_E} f_i p_i, where N_E is the total number of experts, f_i represents the frequency of expert i being selected, and p_i denotes the average gating score of the expert i. Existing MoE training frameworks usually employ the parallel training strategy so that f_i and the LBL are calculated within a micro-batch and then averaged across parallel groups. In essence, a micro-batch for training billion-scale LLMs normally contains very few sequences. So, the micro-batch LBL is almost at the sequence level, and the router is pushed to distribute the token evenly within each sequence. Under this strict constraint, even tokens from a domain-specific sequence (e.g., code) are uniformly routed to all experts, thereby inhibiting expert specialization. In this work, we propose calculating LBL using a global-batch to loose this constraint. Because a global-batch contains much more diverse sequences than a micro-batch, which will encourage load balance at the corpus level. Specifically, we introduce an extra communication step to synchronize f_i across micro-batches and then use it to calculate the LBL. Through experiments on training MoEs-based LLMs (up to 42.8B total parameters and 400B tokens), we surprisingly find that the global-batch LBL strategy yields excellent performance gains in both pre-training perplexity and downstream tasks. Our analysis reveals that the global-batch LBL also greatly improves the domain specialization of MoE experts.

Large language models (LLMs) propel the prosperity of interactive AI applications showcased by ChatGPT that demand timely response of inference services. However, LLM inference is computation intensive and memory intensive, and improper parameter configuration at LLM platforms may exacerbate the inference time. In this paper, we analyze the impact of LLM output token distribution on the inference queueing delay, where the max-token clipping and the batched inference are considered. By formulating an M/G/1 model, we observe that enforcing a maximum output token limit on a very small fraction of inference requests can significantly reduce the queueing delay, and our model facilitates the selection of the optimal limit. For the batch inference, we model the service process as a bulk queue in which the batch processing time is affected by the batch size and the maximum token size inside this batch jointly. The queueing delays of the batching of all buffered requests (dynamic batching), the batching of constant number of requests (fixed batching), and the batching without intra-batch waiting (elastic batching) are derived. Experimental results show that our mathematical models coincide with the event-driven simulations well.

Test-Time Training (TTT) models context dependencies by adapting part of the model's weights (referred to as fast weights) during inference. This fast weight, akin to recurrent states in RNNs, stores temporary memories of past tokens in the current sequence. Existing TTT methods struggled to show effectiveness in handling long-context data, due to their inefficiency on modern GPUs. The TTT layers in many of these approaches operate with extremely low FLOPs utilization (often <5%) because they deliberately apply small online minibatch sizes (e.g., updating fast weights every 16 or 64 tokens). Moreover, a small minibatch implies fine-grained block-wise causal dependencies in the data, unsuitable for data beyond 1D ordered sequences, like sets or N-dimensional grids such as images or videos. In contrast, we pursue the opposite direction by using an extremely large chunk update, ranging from 2K to 1M tokens across tasks of varying modalities, which we refer to as Large Chunk Test-Time Training (LaCT). It improves hardware utilization by orders of magnitude, and more importantly, facilitates scaling of nonlinear state size (up to 40% of model parameters), hence substantially improving state capacity, all without requiring cumbersome and error-prone kernel implementations. It also allows easy integration of sophisticated optimizers, e.g. Muon for online updates. We validate our approach across diverse modalities and tasks, including novel view synthesis with image set, language models, and auto-regressive video diffusion. Our approach can scale up to 14B-parameter AR video diffusion model on sequences up to 56K tokens. In our longest sequence experiment, we perform novel view synthesis with 1 million context length. We hope this work will inspire and accelerate new research in the field of long-context modeling and test-time training. Website: https://tianyuanzhang.com/projects/ttt-done-right

Scaling laws have transformed our understanding of large language models by linking upstream metrics like cross-entropy loss to design factors such as model size, training data, and compute. However, these conventional laws fail to capture downstream task performance, where context plays a critical role. In this work, we propose a straightforward, interpretable framework that jointly models downstream performance as a function of the training compute and the provided context. We empirically validate our framework by fitting it on the observed downstream performance of extended-context variants of Llama-2-7B and Llama-2-13B across 65,500 unique instances spanning three tasks: arithmetic reasoning, common sense reasoning, and machine translation. Our results demonstrate that our framework accurately models in-distribution downstream performance, generalizes across three orders of magnitude in training compute, and reliably extrapolates performance as the amount of context increases. These findings offer valuable insights into the interplay between training compute and context utilization, providing guidance for designing more efficient long-context LLMs for diverse downstream tasks. Our code is available at https://github.com/wang-research-lab/context-scaling.

As the ever-increasing token limits of large language models (LLMs) have enabled long context as input, prompting with single data samples might no longer an efficient way. A straightforward strategy improving efficiency is to batch data within the token limit (e.g., 8k for gpt-3.5-turbo; 32k for GPT-4), which we call BatchPrompt. We have two initial observations for prompting with batched data. First, we find that prompting with batched data in longer contexts will inevitably lead to worse performance, compared to single-data prompting. Second, the performance of the language model is significantly correlated with the positions and order of the batched data, due to the corresponding change in decoder context. To retain efficiency and overcome performance loss, we propose Batch Permutation and Ensembling (BPE), and a novel Self-reflection-guided EArly Stopping (SEAS) technique. Our comprehensive experimental evaluation demonstrates that BPE can boost the performance of BatchPrompt with a striking margin on a range of popular NLP tasks, including question answering (Boolq), textual entailment (RTE), and duplicate questions identification (QQP). These performances are even competitive with/higher than single-data prompting(SinglePrompt), while BatchPrompt requires much fewer LLM calls and input tokens (For SinglePrompt v.s. BatchPrompt with batch size 32, using just 9%-16% the number of LLM calls, Boolq accuracy 90.6% to 90.9% with 27.4% tokens, QQP accuracy 87.2% to 88.4% with 18.6% tokens, RTE accuracy 91.5% to 91.1% with 30.8% tokens). To the best of our knowledge, this is the first work to technically improve prompting efficiency of large language models. We hope our simple yet effective approach will shed light on the future research of large language models. The code will be released.

Over the past decade, the revolution in single-cell sequencing has enabled the simultaneous molecular profiling of various modalities across thousands of individual cells, allowing scientists to investigate the diverse functions of complex tissues and uncover underlying disease mechanisms. Among all the analytical steps, assigning individual cells to specific types is fundamental for understanding cellular heterogeneity. However, this process is usually labor-intensive and requires extensive expert knowledge. Recent advances in large language models (LLMs) have demonstrated their ability to efficiently process and synthesize vast corpora of text to automatically extract essential biological knowledge, such as marker genes, potentially promoting more efficient and automated cell type annotations. To thoroughly evaluate the capability of modern instruction-tuned LLMs in automating the cell type identification process, we introduce SOAR, a comprehensive benchmarking study of LLMs for cell type annotation tasks in single-cell genomics. Specifically, we assess the performance of 8 instruction-tuned LLMs across 11 datasets, spanning multiple cell types and species. Our study explores the potential of LLMs to accurately classify and annotate cell types in single-cell RNA sequencing (scRNA-seq) data, while extending their application to multiomics data through cross-modality translation. Additionally, we evaluate the effectiveness of chain-of-thought (CoT) prompting techniques in generating detailed biological insights during the annotation process. The results demonstrate that LLMs can provide robust interpretations of single-cell data without requiring additional fine-tuning, advancing the automation of cell type annotation in genomics research.

We introduce methods to quantify how Large Language Models (LLMs) encode and store contextual information, revealing that tokens often seen as minor (e.g., determiners, punctuation) carry surprisingly high context. Notably, removing these tokens -- especially stopwords, articles, and commas -- consistently degrades performance on MMLU and BABILong-4k, even if removing only irrelevant tokens. Our analysis also shows a strong correlation between contextualization and linearity, where linearity measures how closely the transformation from one layer's embeddings to the next can be approximated by a single linear mapping. These findings underscore the hidden importance of filler tokens in maintaining context. For further exploration, we present LLM-Microscope, an open-source toolkit that assesses token-level nonlinearity, evaluates contextual memory, visualizes intermediate layer contributions (via an adapted Logit Lens), and measures the intrinsic dimensionality of representations. This toolkit illuminates how seemingly trivial tokens can be critical for long-range understanding.

The escalating demand for long-context applications has intensified the necessity of extending the LLM context windows. Despite recent fine-tuning approaches successfully expanding context lengths, their high memory footprints, especially for activations, present a critical practical limitation. Current parameter-efficient fine-tuning methods prioritize reducing parameter update overhead over addressing activation memory constraints. Similarly, existing sparsity mechanisms improve computational efficiency but overlook activation memory optimization due to the phenomenon of Shadowy Activation. In this paper, we propose LeMo, the first LLM fine-tuning system that explores and exploits a new token-level sparsity mechanism inherent in long-context scenarios, termed Contextual Token Sparsity. LeMo minimizes redundant token involvement by assessing the informativeness of token embeddings while preserving model accuracy. Specifically, LeMo introduces three key techniques: (1) Token Elimination, dynamically identifying and excluding redundant tokens across varying inputs and layers. (2) Pattern Prediction, utilizing well-trained predictors to approximate token sparsity patterns with minimal overhead. (3) Kernel Optimization, employing permutation-free and segment-based strategies to boost system performance. We implement LeMo as an end-to-end fine-tuning system compatible with various LLM architectures and other optimization techniques. Comprehensive evaluations demonstrate that LeMo reduces memory consumption by up to 1.93x and achieves up to 1.36x speedups, outperforming state-of-the-art fine-tuning systems.

Recurrent large language models that compete with Transformers in language modeling perplexity are emerging at a rapid rate (e.g., Mamba, RWKV). Excitingly, these architectures use a constant amount of memory during inference. However, due to the limited memory, recurrent LMs cannot recall and use all the information in long contexts leading to brittle in-context learning (ICL) quality. A key challenge for efficient LMs is selecting what information to store versus discard. In this work, we observe the order in which information is shown to the LM impacts the selection difficulty. To formalize this, we show that the hardness of information recall reduces to the hardness of a problem called set disjointness (SD), a quintessential problem in communication complexity that requires a streaming algorithm (e.g., recurrent model) to decide whether inputted sets are disjoint. We empirically and theoretically show that the recurrent memory required to solve SD changes with set order, i.e., whether the smaller set appears first in-context. Our analysis suggests, to mitigate the reliance on data order, we can put information in the right order in-context or process prompts non-causally. Towards that end, we propose: (1) JRT-Prompt, where context gets repeated multiple times in the prompt, effectively showing the model all data orders. This gives 11.0 pm 1.3 points of improvement, averaged across 16 recurrent LMs and the 6 ICL tasks, with 11.9times higher throughput than FlashAttention-2 for generation prefill (length 32k, batch size 16, NVidia H100). We then propose (2) JRT-RNN, which uses non-causal prefix-linear-attention to process prompts and provides 99% of Transformer quality at 360M params., 30B tokens and 96% at 1.3B params., 50B tokens on average across the tasks, with 19.2times higher throughput for prefill than FA2.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Biological protocols are fundamental to reproducible and safe life science research. While LLMs excel on general tasks, their systematic evaluation on these highly specialized, accuracy-critical, and inherently procedural texts remains limited. In this work, we present BioProBench, the first large-scale, integrated multi-task benchmark for biological protocol understanding and reasoning. While limited benchmarks have touched upon specific aspects like protocol QA, BioProBench provides a comprehensive suite of five core tasks: Protocol Question Answering, Step Ordering, Error Correction, Protocol Generation, and Protocol Reasoning, enabling a holistic evaluation of LLMs on procedural biological texts. Built upon 27K original protocols, it yields nearly 556K high-quality structured instances. We evaluate 12 mainstream open/closed-source LLMs on BioProBench. Experimental results reveal that while top models preform well on surface understanding tasks, struggle significantly with deep reasoning and structured generation tasks like ordering and generation. Furthermore, model comparisons reveal diverse performance: certain open-source models approach closed-source levels on some tasks, yet bio-specific small models lag behind general LLMs, indicating limitations on complex procedural content. Overall, our findings underscore that procedural reasoning within biological protocols represents a significant challenge for current LLMs. BioProBench serves as a standardized framework to diagnose these specific limitations and guide the development of AI systems better equipped for safely automating complex scientific procedures. The code and data are available at: https://github.com/YuyangSunshine/bioprotocolbench and https://huggingface.co/datasets/GreatCaptainNemo/BioProBench.

Large language models have been widely adopted across different tasks, but their auto-regressive generation nature often leads to inefficient resource utilization during inference. While batching is commonly used to increase throughput, performance gains plateau beyond a certain batch size, especially with smaller models, a phenomenon that existing literature typically explains as a shift to the compute-bound regime. In this paper, through an in-depth GPU-level analysis, we reveal that large-batch inference remains memory-bound, with most GPU compute capabilities underutilized due to DRAM bandwidth saturation as the primary bottleneck. To address this, we propose a Batching Configuration Advisor (BCA) that optimizes memory allocation, reducing GPU memory requirements with minimal impact on throughput. The freed memory and underutilized GPU compute capabilities can then be leveraged by concurrent workloads. Specifically, we use model replication to improve serving throughput and GPU utilization. Our findings challenge conventional assumptions about LLM inference, offering new insights and practical strategies for improving resource utilization, particularly for smaller language models.

Long context capability is a crucial competency for large language models (LLMs) as it mitigates the human struggle to digest long-form texts. This capability enables complex task-solving scenarios such as book summarization, code assistance, and many more tasks that are traditionally manpower-intensive. However, transformer-based LLMs face significant challenges with long context input due to the growing size of the KV cache and the intrinsic complexity of attending to extended inputs; where multiple schools of efficiency-driven approaches -- such as KV cache quantization, token dropping, prompt compression, linear-time sequence models, and hybrid architectures -- have been proposed to produce efficient yet long context-capable models. Despite these advancements, no existing work has comprehensively benchmarked these methods in a reasonably aligned environment. In this work, we fill this gap by providing a taxonomy of current methods and evaluating 10+ state-of-the-art approaches across seven categories of long context tasks. Our work reveals numerous previously unknown phenomena and offers insights -- as well as a friendly workbench -- for the future development of long context-capable LLMs. The source code will be available at https://github.com/henryzhongsc/longctx_bench

Automatic Speech Recognition (ASR) has been extensively investigated, yet prior evaluative efforts have largely been restricted to contextless paradigms. This constraint stems from the limited proficiency of conventional ASR models in context modeling and their deficiency in memory and reasoning based on world knowledge. Recent breakthroughs in the development of Large Language Models (LLMs) and corresponding Large Audio Language Models (LALMs) have markedly enhanced the visibility of general artificial intelligence capabilities. Consequently, there exists a compelling need for a benchmark that can evaluate both the generality and intelligence of ASR systems. To address this gap, we propose ContextASR-Bench: a comprehensive, large-scale benchmark designed to assess contextual speech recognition. This benchmark encompasses up to 40,000 data entries across over 10 domains, enabling a thorough evaluation of model performance in scenarios that omit or incorporate coarse-grained or fine-grained contextual information. Moreover, diverging from conventional ASR evaluations, our benchmark includes an analysis of model efficacy in recognizing named entities mentioned within the auditory input. Our extensive evaluation highlights that LALMs, with strong world knowledge and context learning capabilities, outperform conventional ASR models by a large margin. The dataset and evaluation code have been released at https://github.com/MrSupW/ContextASR-Bench.

Large language models (LLMs) have had a huge impact on society due to their impressive capabilities and vast knowledge of the world. Various applications and tools have been created that allow users to interact with these models in a black-box scenario. However, one limitation of this scenario is that users cannot modify the internal knowledge of the model, and the only way to add or modify internal knowledge is by explicitly mentioning it to the model during the current interaction. This learning process is called in-context training, and it refers to training that is confined to the user's current session or context. In-context learning has significant applications, but also has limitations that are seldom studied. In this paper, we present a study that shows how the model can suffer from interference between information that continually flows in the context, causing it to forget previously learned knowledge, which can reduce the model's performance. Along with showing the problem, we propose an evaluation benchmark based on the bAbI dataset.

Masked image modelling (MIM) is a powerful self-supervised representation learning paradigm, whose potential has not been widely demonstrated in medical image analysis. In this work, we show the capacity of MIM to capture rich semantic representations of Haemotoxylin & Eosin (H&E)-stained images at the nuclear level. Inspired by Bidirectional Encoder representation from Image Transformers (BEiT), we split the images into smaller patches and generate corresponding discrete visual tokens. In addition to the regular grid-based patches, typically used in visual Transformers, we introduce patches of individual cell nuclei. We propose positional encoding of the irregular distribution of these structures within an image. We pre-train the model in a self-supervised manner on H&E-stained whole-slide images of diffuse large B-cell lymphoma, where cell nuclei have been segmented. The pre-training objective is to recover the original discrete visual tokens of the masked image on the one hand, and to reconstruct the visual tokens of the masked object instances on the other. Coupling these two pre-training tasks allows us to build powerful, context-aware representations of nuclei. Our model generalizes well and can be fine-tuned on downstream classification tasks, achieving improved cell classification accuracy on PanNuke dataset by more than 5% compared to current instance segmentation methods.

Long-context LLMs have enabled numerous downstream applications but also introduced significant challenges related to computational and memory efficiency. To address these challenges, optimizations for long-context inference have been developed, centered around the KV cache. However, existing benchmarks often evaluate in single-request, neglecting the full lifecycle of the KV cache in real-world use. This oversight is particularly critical, as KV cache reuse has become widely adopted in LLMs inference frameworks, such as vLLM and SGLang, as well as by LLM providers, including OpenAI, Microsoft, Google, and Anthropic. To address this gap, we introduce SCBench(SharedContextBench), a comprehensive benchmark for evaluating long-context methods from a KV cachecentric perspective: 1) KV cache generation, 2) KV cache compression, 3) KV cache retrieval, 4) KV cache loading. Specifically, SCBench uses test examples with shared context, ranging 12 tasks with two shared context modes, covering four categories of long-context capabilities: string retrieval, semantic retrieval, global information, and multi-task. With it, we provide an extensive KV cache-centric analysis of eight categories long-context solutions, including Gated Linear RNNs, Mamba-Attention hybrids, and efficient methods such as sparse attention, KV cache dropping, quantization, retrieval, loading, and prompt compression. The evaluation is conducted on 8 long-context LLMs. Our findings show that sub-O(n) memory methods suffer in multi-turn scenarios, while sparse encoding with O(n) memory and sub-O(n^2) pre-filling computation perform robustly. Dynamic sparsity yields more expressive KV caches than static patterns, and layer-level sparsity in hybrid architectures reduces memory usage with strong performance. Additionally, we identify attention distribution shift issues in long-generation scenarios. https://aka.ms/SCBench.

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations. In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens. We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological data.

Large Language Models (LLMs) face significant challenges in long-context processing, including quadratic computational costs, information forgetting, and the context fragmentation inherent in retrieval-augmented generation (RAG). We propose a cognitively inspired framework for efficient long-context inference based on chunk-wise compression and selective memory recall, rather than processing all raw tokens. The framework segments long inputs into chunks and encodes each chunk into compressed memory representations using a learned compressor. A gating module dynamically selects relevant memory blocks, which are then iteratively processed by a reasoning module with an evolving working memory to solve downstream tasks. The compressor and reasoner are jointly optimized via end-to-end reinforcement learning, while the gating module is trained separately as a classifier. Experimental results show that the proposed method achieves competitive accuracy on multi-hop reasoning benchmarks such as RULER-HQA, extrapolates context length from 7K to 1.75M tokens, and offers a favorable accuracy-efficiency trade-off compared to strong long-context baselines. In particular, it achieves up to a 2 times reduction in peak GPU memory usage and a 6 times inference speedup over MemAgent.

Extending the context length (i.e., the maximum supported sequence length) of LLMs is of paramount significance. To facilitate long context training of LLMs, sequence parallelism has emerged as an essential technique, which scatters each input sequence across multiple devices and necessitates communication to process the sequence. In essence, existing sequence parallelism methods assume homogeneous sequence lengths (i.e., all input sequences are equal in length) and therefore leverages a single, static scattering strategy for all input sequences. However, in reality, the sequence lengths in LLM training corpora exhibit substantial variability, often following a long-tail distribution, which leads to workload heterogeneity. In this paper, we show that employing a single, static strategy results in inefficiency and resource under-utilization, highlighting the need for adaptive approaches to handle the heterogeneous workloads across sequences. To address this, we propose a heterogeneity-adaptive sequence parallelism method. For each training step, our approach captures the variability in sequence lengths and assigns the optimal combination of scattering strategies based on workload characteristics. We model this problem as a linear programming optimization and design an efficient and effective solver to find the optimal solution. Furthermore, we implement our method in a high-performance system that supports adaptive parallelization in distributed LLM training. Experimental results demonstrate that our system outperforms state-of-the-art training frameworks by up to 1.98x.

Pre-trained language models (PLMs) have revolutionized scientific research, yet their application to single-cell analysis remains limited. Text PLMs cannot process single-cell RNA sequencing data, while cell PLMs lack the ability to handle free text, restricting their use in multimodal tasks. Existing efforts to bridge these modalities often suffer from information loss or inadequate single-modal pre-training, leading to suboptimal performances. To address these challenges, we propose Single-Cell MultiModal Generative Pre-trained Transformer (scMMGPT), a unified PLM for joint cell and text modeling. scMMGPT effectively integrates the state-of-the-art cell and text PLMs, facilitating cross-modal knowledge sharing for improved performance. To bridge the text-cell modality gap, scMMGPT leverages dedicated cross-modal projectors, and undergoes extensive pre-training on 27 million cells -- the largest dataset for multimodal cell-text PLMs to date. This large-scale pre-training enables scMMGPT to excel in joint cell-text tasks, achieving an 84\% relative improvement of textual discrepancy for cell description generation, 20.5\% higher accuracy for cell type annotation, and 4\% improvement in k-NN accuracy for text-conditioned pseudo-cell generation, outperforming baselines.

Large Language Models (LLMs) are primarily designed for batch processing. Existing methods for adapting LLMs to streaming rely either on expensive re-encoding or specialized architectures with limited scalability. This work identifies three key mismatches in adapting batch-oriented LLMs to streaming: (1) input-attention, (2) output-attention, and (3) position-ID mismatches. While it is commonly assumed that the latter two mismatches require frequent re-encoding, our analysis reveals that only the input-attention mismatch significantly impacts performance, indicating re-encoding outputs is largely unnecessary. To better understand this discrepancy with the common assumption, we provide the first comprehensive analysis of the impact of position encoding on LLMs in streaming, showing that preserving relative positions within source and target contexts is more critical than maintaining absolute order. Motivated by the above analysis, we introduce a group position encoding paradigm built on batch architectures to enhance consistency between streaming and batch modes. Extensive experiments on cross-lingual and cross-modal tasks demonstrate that our method outperforms existing approaches. Our method requires no architectural modifications, exhibits strong generalization in both streaming and batch modes. The code is available at repository https://github.com/EIT-NLP/StreamingLLM.

We present context parallelism for long-context large language model inference, which achieves near-linear scaling for long-context prefill latency with up to 128 H100 GPUs across 16 nodes. Particularly, our method achieves 1M context prefill with Llama3 405B model in 77s (93% parallelization efficiency, 63% FLOPS utilization) and 128K context prefill in 3.8s. We develop two lossless exact ring attention variants: pass-KV and pass-Q to cover a wide range of use cases with the state-of-the-art performance: full prefill, persistent KV prefill and decode. Benchmarks on H100 GPU hosts inter-connected with RDMA and TCP both show similar scalability for long-context prefill, demonstrating that our method scales well using common commercial data center with medium-to-low inter-host bandwidth.

Transformer-based large language models (LLMs) have achieved remarkable success, yet their standard attention mechanism incurs quadratic computation and memory costs with respect to sequence length, posing a major bottleneck for long-context training. Prior work tackles this challenge along two directions: (1) kernel-level optimizations, which accelerate dense and sparse attention operators; and (2) module-level strategies, often referred to as distributed attention or context parallel training, which scale attention across multiple devices. However, systematic evaluation still remains limited: operator-level comparisons are often incomplete, while context parallel strategies are typically framework-specific, with unclear performance analysis across contexts. To address these gaps, we propose a unified benchmark that integrates representative attention kernels and context parallel mechanisms with a modular and extensible interface for evaluation. The benchmark evaluates methods along two critical dimensions: (1) attention mask patterns, which strongly affect efficiency, scalability, and usability, and (2) sequence length and distributed scale, which determine performance under extreme long-context training. Through comprehensive experiments on the cluster of up to 96 GPUs, our benchmark enables reproducible comparisons, highlights method-specific trade-offs, and provides practical guidance for designing and deploying attention mechanisms in long-context LLM training.

Large language models (LLMs) have emerged due to their capability to generate high-quality content across diverse contexts. To reduce their explosively increasing demands for computing resources, a mixture of experts (MoE) has emerged. The MoE layer enables exploiting a huge number of parameters with less computation. Applying state-of-the-art continuous batching increases throughput; however, it leads to frequent DRAM access in the MoE and attention layers. We observe that conventional computing devices have limitations when processing the MoE and attention layers, which dominate the total execution time and exhibit low arithmetic intensity (Op/B). Processing MoE layers only with devices targeting low-Op/B such as processing-in-memory (PIM) architectures is challenging due to the fluctuating Op/B in the MoE layer caused by continuous batching. To address these challenges, we propose Duplex, which comprises xPU tailored for high-Op/B and Logic-PIM to effectively perform low-Op/B operation within a single device. Duplex selects the most suitable processor based on the Op/B of each layer within LLMs. As the Op/B of the MoE layer is at least 1 and that of the attention layer has a value of 4-8 for grouped query attention, prior PIM architectures are not efficient, which place processing units inside DRAM dies and only target extremely low-Op/B (under one) operations. Based on recent trends, Logic-PIM adds more through-silicon vias (TSVs) to enable high-bandwidth communication between the DRAM die and the logic die and place powerful processing units on the logic die, which is best suited for handling low-Op/B operations ranging from few to a few dozens. To maximally utilize the xPU and Logic-PIM, we propose expert and attention co-processing.

We introduce CaLMFlow (Causal Language Models for Flow Matching), a novel framework that casts flow matching as a Volterra integral equation (VIE), leveraging the power of large language models (LLMs) for continuous data generation. CaLMFlow enables the direct application of LLMs to learn complex flows by formulating flow matching as a sequence modeling task, bridging discrete language modeling and continuous generative modeling. Our method implements tokenization across space and time, thereby solving a VIE over these domains. This approach enables efficient handling of high-dimensional data and outperforms ODE solver-dependent methods like conditional flow matching (CFM). We demonstrate CaLMFlow's effectiveness on synthetic and real-world data, including single-cell perturbation response prediction, showcasing its ability to incorporate textual context and generalize to unseen conditions. Our results highlight LLM-driven flow matching as a promising paradigm in generative modeling, offering improved scalability, flexibility, and context-awareness.

Cell segmentation is a major bottleneck in extracting quantitative single-cell information from microscopy data. The challenge is exasperated in the setting of microstructured environments. While deep learning approaches have proven useful for general cell segmentation tasks, existing segmentation tools for the yeast-microstructure setting rely on traditional machine learning approaches. Here we present convolutional neural networks trained for multiclass segmenting of individual yeast cells and discerning these from cell-similar microstructures. We give an overview of the datasets recorded for training, validating and testing the networks, as well as a typical use-case. We showcase the method's contribution to segmenting yeast in microstructured environments with a typical synthetic biology application in mind. The models achieve robust segmentation results, outperforming the previous state-of-the-art in both accuracy and speed. The combination of fast and accurate segmentation is not only beneficial for a posteriori data processing, it also makes online monitoring of thousands of trapped cells or closed-loop optimal experimental design feasible from an image processing perspective.

A recent trend in LLMs is developing recurrent sub-quadratic models that improve long-context processing efficiency. We investigate leading large long-context models, focusing on how their fixed-size recurrent memory affects their performance. Our experiments reveal that, even when these models are trained for extended contexts, their use of long contexts remains underutilized. Specifically, we demonstrate that a chunk-based inference procedure, which identifies and processes only the most relevant portion of the input can mitigate recurrent memory failures and be effective for many long-context tasks: On LongBench, our method improves the overall performance of Falcon3-Mamba-Inst-7B by 14%, Falcon-Mamba-Inst-7B by 28%, RecurrentGemma-IT-9B by 50%, and RWKV6-Finch-7B by 51%. Surprisingly, this simple approach also leads to state-of-the-art results in the challenging LongBench v2 benchmark, showing competitive performance with equivalent size Transformers. Furthermore, our findings raise questions about whether recurrent models genuinely exploit long-range dependencies, as our single-chunk strategy delivers stronger performance - even in tasks that presumably require cross-context relations.

While the use of bottom-up local operators in convolutional neural networks (CNNs) matches well some of the statistics of natural images, it may also prevent such models from capturing contextual long-range feature interactions. In this work, we propose a simple, lightweight approach for better context exploitation in CNNs. We do so by introducing a pair of operators: gather, which efficiently aggregates feature responses from a large spatial extent, and excite, which redistributes the pooled information to local features. The operators are cheap, both in terms of number of added parameters and computational complexity, and can be integrated directly in existing architectures to improve their performance. Experiments on several datasets show that gather-excite can bring benefits comparable to increasing the depth of a CNN at a fraction of the cost. For example, we find ResNet-50 with gather-excite operators is able to outperform its 101-layer counterpart on ImageNet with no additional learnable parameters. We also propose a parametric gather-excite operator pair which yields further performance gains, relate it to the recently-introduced Squeeze-and-Excitation Networks, and analyse the effects of these changes to the CNN feature activation statistics.

Computational microscopy, in which hardware and algorithms of an imaging system are jointly designed, shows promise for making imaging systems that cost less, perform more robustly, and collect new types of information. Often, the performance of computational imaging systems, especially those that incorporate machine learning, is sample-dependent. Thus, standardized datasets are an essential tool for comparing the performance of different approaches. Here, we introduce the Berkeley Single Cell Computational Microscopy (BSCCM) dataset, which contains over ~12,000,000 images of 400,000 of individual white blood cells. The dataset contains images captured with multiple illumination patterns on an LED array microscope and fluorescent measurements of the abundance of surface proteins that mark different cell types. We hope this dataset will provide a valuable resource for the development and testing of new algorithms in computational microscopy and computer vision with practical biomedical applications.

In this work, we propose FastCoT, a model-agnostic framework based on parallel decoding without any further training of an auxiliary model or modification to the LLM itself. FastCoT uses a size-varying context window whose size changes with position to conduct parallel decoding and auto-regressive decoding simultaneously, thus fully utilizing GPU computation resources. In FastCoT, the parallel decoding part provides the LLM with a quick glance of the future composed of approximate tokens, which could lead to faster answers compared to regular autoregressive decoding used by causal transformers. We also provide an implementation of parallel decoding within LLM, which supports KV-cache generation and batch processing. Through extensive experiments, we demonstrate that FastCoT saves inference time by nearly 20% with only a negligible performance drop compared to the regular approach. Additionally, we show that the context window size exhibits considerable robustness for different tasks.

Data curation is an essential component of large-scale pretraining. In this work, we demonstrate that jointly selecting batches of data is more effective for learning than selecting examples independently. Multimodal contrastive objectives expose the dependencies between data and thus naturally yield criteria for measuring the joint learnability of a batch. We derive a simple and tractable algorithm for selecting such batches, which significantly accelerate training beyond individually-prioritized data points. As performance improves by selecting from larger super-batches, we also leverage recent advances in model approximation to reduce the associated computational overhead. As a result, our approach--multimodal contrastive learning with joint example selection (JEST)--surpasses state-of-the-art models with up to 13times fewer iterations and 10times less computation. Essential to the performance of JEST is the ability to steer the data selection process towards the distribution of smaller, well-curated datasets via pretrained reference models, exposing the level of data curation as a new dimension for neural scaling laws.

LLM-based reasoning models have enabled the development of agentic systems that act as co-scientists, assisting in multi-step scientific analysis. However, evaluating these systems is challenging, as it requires realistic, end-to-end research scenarios that integrate data analysis, interpretation, and the generation of new insights from the experimental data. To address this limitation, we introduce HeurekaBench, a framework to create benchmarks with exploratory, open-ended research questions for experimental datasets. Each such question is grounded in a scientific study and its corresponding code repository, and is created using a semi-automated pipeline that leverages multiple LLMs to extract insights and generate candidate workflows, which are then verified against reported findings. We instantiate the framework in single-cell biology to obtain sc-HeurekaBench benchmark and use it to compare state-of-the-art single-cell agents. We further showcase the benefits of our benchmark for quantitatively analyzing current design choices in agentic systems. We find that the addition of a critic module can improve ill-formed responses for open-source LLM-based agents by up to 22% and close the gap with their closed-source counterparts. Overall, HeurekaBench sets a path toward rigorous, end-to-end evaluation of scientific agents, grounding benchmark construction in real scientific workflows.

As large language models (LLMs) take on more complex tasks, their inputs incorporate longer contexts to respond to questions that require domain knowledge or user-specific conversational histories. Yet, using long contexts poses a challenge for responsive LLM systems, as nothing can be generated until all the contexts are fetched to and processed by the LLM. Existing systems optimize only the computation delay in context processing (e.g., by caching intermediate key-value features of the text context) but often cause longer network delays in context fetching (e.g., key-value features consume orders of magnitude larger bandwidth than the text context). This paper presents CacheGen to minimize the delays in fetching and processing contexts for LLMs. CacheGen reduces the bandwidth needed for transmitting long contexts' key-value (KV) features through a novel encoder that compresses KV features into more compact bitstream representations. The encoder combines adaptive quantization with a tailored arithmetic coder, taking advantage of the KV features' distributional properties, such as locality across tokens. Furthermore, CacheGen minimizes the total delay in fetching and processing a context by using a controller that determines when to load the context as compressed KV features or raw text and picks the appropriate compression level if loaded as KV features. We test CacheGen on three models of various sizes and three datasets of different context lengths. Compared to recent methods that handle long contexts, CacheGen reduces bandwidth usage by 3.7-4.3x and the total delay in fetching and processing contexts by 2.7-3x while maintaining similar LLM performance on various tasks as loading the text contexts.

Efficiently processing long sequences with Transformer models usually requires splitting the computations across accelerators via context parallelism. The dominant approaches in this family of methods, such as Ring Attention or DeepSpeed Ulysses, enable scaling over the context dimension but do not focus on memory efficiency, which limits the sequence lengths they can support. More advanced techniques, such as Fully Pipelined Distributed Transformer or activation offloading, can further extend the possible context length at the cost of training throughput. In this paper, we present UPipe, a simple yet effective context parallelism technique that performs fine-grained chunking at the attention head level. This technique significantly reduces the activation memory usage of self-attention, breaking the activation memory barrier and unlocking much longer context lengths. Our approach reduces intermediate tensor memory usage in the attention layer by as much as 87.5% for 32B Transformers, while matching previous context parallelism techniques in terms of training speed. UPipe can support the context length of 5M tokens when training Llama3-8B on a single 8timesH100 node, improving upon prior methods by over 25%.

Large Language Models (LLMs) are increasingly deployed in scenarios demanding ultra-long context reasoning, such as agentic workflows and deep research understanding. However, long-context inference is constrained by the KV cache, a transient memory structure that grows linearly with sequence length and batch size, quickly dominating GPU memory usage. Existing memory reduction techniques, including eviction and quantization, often rely on static heuristics and suffer from degraded quality under tight budgets. In this paper, we propose ARKV, a lightweight and adaptive framework that dynamically allocates precision levels to cached tokens based on per-layer attention dynamics and token-level importance. During a short prefill phase, ARKV estimates the original quantization (OQ) ratio of each layer by computing statistical scores such as attention entropy, variance and kurtosis. During decoding, tokens are assigned to one of three states, Original (full precision), Quantization (low precision), or Eviction, according to a fast heavy-hitter scoring strategy. Our experiments on LLaMA3 and Qwen3 models across diverse long- and short-context tasks demonstrate that ARKV preserves ~97% of baseline accuracy on long-context benchmarks while reducing KV memory usage by 4x, with minimal throughput loss. On short-context tasks, ARKV matches full-precision baselines; on GSM8K math reasoning, it significantly outperforms uniform quantization. These results highlight the practical viability of ARKV for scalable LLM deployment, offering fine-grained, data-driven memory control without retraining or architectural modifications. The source code and artifacts can be found in: https://github.com/Large-scale-Sustainable-Computing-LSC/ARKV

Large Language Models (LLMs) face significant computational challenges when processing long contexts due to the quadratic complexity of self-attention. While soft context compression methods, which map input text to smaller latent representations, have shown promise, their real-world adoption is limited. Existing techniques typically compress the context as a single unit, which leads to quadratic compression complexity and an inability to reuse computations across queries with overlapping contexts. In this work, we introduce CompLLM, a soft compression technique designed for practical deployment. Instead of processing the context holistically, CompLLM divides it into segments and compresses each one independently. This simple design choice yields three critical properties: efficiency, as the compression step scales linearly with the context length; scalability, enabling models trained on short sequences (e.g., 1k tokens) to generalize to contexts of 100k tokens; and reusability, allowing compressed segments to be cached and reused across different queries. Our experiments show that with a 2x compression rate, at high context lengths CompLLM speeds up Time To First Token (TTFT) by up to 4x and reduces the KV cache size by 50%. Furthermore, CompLLM achieves performance comparable to that obtained with the uncompressed context, and even surpasses it on very long sequences, demonstrating its effectiveness and practical utility.

The performance of Large Language Models (LLMs) is fundamentally determined by the contextual information provided during inference. This survey introduces Context Engineering, a formal discipline that transcends simple prompt design to encompass the systematic optimization of information payloads for LLMs. We present a comprehensive taxonomy decomposing Context Engineering into its foundational components and the sophisticated implementations that integrate them into intelligent systems. We first examine the foundational components: context retrieval and generation, context processing and context management. We then explore how these components are architecturally integrated to create sophisticated system implementations: retrieval-augmented generation (RAG), memory systems and tool-integrated reasoning, and multi-agent systems. Through this systematic analysis of over 1300 research papers, our survey not only establishes a technical roadmap for the field but also reveals a critical research gap: a fundamental asymmetry exists between model capabilities. While current models, augmented by advanced context engineering, demonstrate remarkable proficiency in understanding complex contexts, they exhibit pronounced limitations in generating equally sophisticated, long-form outputs. Addressing this gap is a defining priority for future research. Ultimately, this survey provides a unified framework for both researchers and engineers advancing context-aware AI.

High-content screening (HCS) assays based on high-throughput microscopy techniques such as Cell Painting have enabled the interrogation of cells' morphological responses to perturbations at an unprecedented scale. The collection of such data promises to facilitate a better understanding of the relationships between different perturbations and their effects on cellular state. Towards achieving this goal, recent advances in cross-modal contrastive learning could, in theory, be leveraged to learn a unified latent space that aligns perturbations with their corresponding morphological effects. However, the application of such methods to HCS data is not straightforward due to substantial differences in the semantics of Cell Painting images compared to natural images, and the difficulty of representing different classes of perturbations (e.g., small molecule vs CRISPR gene knockout) in a single latent space. In response to these challenges, here we introduce CellCLIP, a cross-modal contrastive learning framework for HCS data. CellCLIP leverages pre-trained image encoders coupled with a novel channel encoding scheme to better capture relationships between different microscopy channels in image embeddings, along with natural language encoders for representing perturbations. Our framework outperforms current open-source models, demonstrating the best performance in both cross-modal retrieval and biologically meaningful downstream tasks while also achieving significant reductions in computation time.

Diffusion models are a new class of generative models, and have dramatically promoted image generation with unprecedented quality and diversity. Existing diffusion models mainly try to reconstruct input image from a corrupted one with a pixel-wise or feature-wise constraint along spatial axes. However, such point-based reconstruction may fail to make each predicted pixel/feature fully preserve its neighborhood context, impairing diffusion-based image synthesis. As a powerful source of automatic supervisory signal, context has been well studied for learning representations. Inspired by this, we for the first time propose ConPreDiff to improve diffusion-based image synthesis with context prediction. We explicitly reinforce each point to predict its neighborhood context (i.e., multi-stride features/tokens/pixels) with a context decoder at the end of diffusion denoising blocks in training stage, and remove the decoder for inference. In this way, each point can better reconstruct itself by preserving its semantic connections with neighborhood context. This new paradigm of ConPreDiff can generalize to arbitrary discrete and continuous diffusion backbones without introducing extra parameters in sampling procedure. Extensive experiments are conducted on unconditional image generation, text-to-image generation and image inpainting tasks. Our ConPreDiff consistently outperforms previous methods and achieves a new SOTA text-to-image generation results on MS-COCO, with a zero-shot FID score of 6.21.

Identifying subtle phenotypic variations in cellular images is critical for advancing biological research and accelerating drug discovery. These variations are often masked by the inherent cellular heterogeneity, making it challenging to distinguish differences between experimental conditions. Recent advancements in deep generative models have demonstrated significant potential for revealing these nuanced phenotypes through image translation, opening new frontiers in cellular and molecular biology as well as the identification of novel biomarkers. Among these generative models, diffusion models stand out for their ability to produce high-quality, realistic images. However, training diffusion models typically requires large datasets and substantial computational resources, both of which can be limited in biological research. In this work, we propose a novel approach that leverages pre-trained latent diffusion models to uncover subtle phenotypic changes. We validate our approach qualitatively and quantitatively on several small datasets of microscopy images. Our findings reveal that our approach enables effective detection of phenotypic variations, capturing both visually apparent and imperceptible differences. Ultimately, our results highlight the promising potential of this approach for phenotype detection, especially in contexts constrained by limited data and computational capacity.

This paper presents advancements in automated early-stage prediction of the success of reprogramming human induced pluripotent stem cells (iPSCs) as a potential source for regenerative cell therapies.The minuscule success rate of iPSC-reprogramming of around 0.01% to 0.1% makes it labor-intensive, time-consuming, and exorbitantly expensive to generate a stable iPSC line. Since that requires culturing of millions of cells and intense biological scrutiny of multiple clones to identify a single optimal clone. The ability to reliably predict which cells are likely to establish as an optimal iPSC line at an early stage of pluripotency would therefore be ground-breaking in rendering this a practical and cost-effective approach to personalized medicine. Temporal information about changes in cellular appearance over time is crucial for predicting its future growth outcomes. In order to generate this data, we first performed continuous time-lapse imaging of iPSCs in culture using an ultra-high resolution microscope. We then annotated the locations and identities of cells in late-stage images where reliable manual identification is possible. Next, we propagated these labels backwards in time using a semi-automated tracking system to obtain labels for early stages of growth. Finally, we used this data to train deep neural networks to perform automatic cell segmentation and classification. Our code and data are available at https://github.com/abhineet123/ipsc_prediction.

Efficient long-context LLM deployment is stalled by a dichotomy between amortized compression, which struggles with out-of-distribution generalization, and Test-Time Training, which incurs prohibitive synthetic data costs and requires modifying model weights, creating stateful parameters that complicate concurrent serving. We propose Latent Context Compilation, a framework that fundamentally shifts context processing from adaptation to compilation. By utilizing a disposable LoRA module as a compiler, we distill long contexts into compact buffer tokens -- stateless, portable memory artifacts that are plug-and-play compatible with frozen base models. Crucially, we introduce a self-aligned optimization strategy that eliminates the need for synthetic context-relevant QA pairs. By regularizing context reconstruction task with context-agnostic random queries, we force compressed tokens to reside within the model's existing instruction-following manifold. Experiments with Llama-3.1-8B demonstrate that Latent Context Compilation preserves fine-grained details and reasoning capabilities where prior methods falter, effectively decoupling memory density from model parameters even at a 16x compression ratio.

We propose Context Diffusion, a diffusion-based framework that enables image generation models to learn from visual examples presented in context. Recent work tackles such in-context learning for image generation, where a query image is provided alongside context examples and text prompts. However, the quality and fidelity of the generated images deteriorate when the prompt is not present, demonstrating that these models are unable to truly learn from the visual context. To address this, we propose a novel framework that separates the encoding of the visual context and preserving the structure of the query images. This results in the ability to learn from the visual context and text prompts, but also from either one of them. Furthermore, we enable our model to handle few-shot settings, to effectively address diverse in-context learning scenarios. Our experiments and user study demonstrate that Context Diffusion excels in both in-domain and out-of-domain tasks, resulting in an overall enhancement in image quality and fidelity compared to counterpart models.

Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose SToFM, a multi-scale Spatial Transcriptomics Foundation Model. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct SToCorpus-88M, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data through capturing and integrating multi-scale information.

Detecting and classifying cells in histopathology H\&E stained whole-slide images is a core task in computational pathology, as it provides valuable insight into the tumor microenvironment. In this work we investigate the impact of ground truth formats on the models performance. Additionally, cell-tissue interactions are considered by providing tissue segmentation predictions as input to the cell detection model. We find that a "soft", probability-map instance segmentation ground truth leads to best model performance. Combined with cell-tissue interaction and test-time augmentation our Soft Cell-Tissue-Model (SoftCTM) achieves 0.7172 mean F1-Score on the Overlapped Cell On Tissue (OCELOT) test set, achieving the third best overall score in the OCELOT 2023 Challenge. The source code for our approach is made publicly available at https://github.com/lely475/ocelot23algo.

Efficient Human Epithelial-2 (HEp-2) cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper presents an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. This paper elaborates the important components of this framework, discusses multiple key factors that impact the efficiency of training a deep CNN, and systematically compares this framework with the well-established image classification models in the literature. Experiments on benchmark datasets show that i) the proposed framework can effectively outperform existing models by properly applying data augmentation; ii) our CNN-based framework demonstrates excellent adaptability across different datasets, which is highly desirable for classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014.

Large language models (LLMs) with hundreds of billions of parameters have sparked a new wave of exciting AI applications. However, they are computationally expensive at inference time. Sparsity is a natural approach to reduce this cost, but existing methods either require costly retraining, have to forgo LLM's in-context learning ability, or do not yield wall-clock time speedup on modern hardware. We hypothesize that contextual sparsity, which are small, input-dependent sets of attention heads and MLP parameters that yield approximately the same output as the dense model for a given input, can address these issues. We show that contextual sparsity exists, that it can be accurately predicted, and that we can exploit it to speed up LLM inference in wall-clock time without compromising LLM's quality or in-context learning ability. Based on these insights, we propose DejaVu, a system that uses a low-cost algorithm to predict contextual sparsity on the fly given inputs to each layer, along with an asynchronous and hardware-aware implementation that speeds up LLM inference. We validate that DejaVu can reduce the inference latency of OPT-175B by over 2X compared to the state-of-the-art FasterTransformer, and over 6X compared to the widely used Hugging Face implementation, without compromising model quality. The code is available at https://github.com/FMInference/DejaVu.

Recent advances in video generation have opened new avenues for macroscopic simulation of complex dynamic systems, but their application to microscopic phenomena remains largely unexplored. Microscale simulation holds great promise for biomedical applications such as drug discovery, organ-on-chip systems, and disease mechanism studies, while also showing potential in education and interactive visualization. In this work, we introduce MicroWorldBench, a multi-level rubric-based benchmark for microscale simulation tasks. MicroWorldBench enables systematic, rubric-based evaluation through 459 unique expert-annotated criteria spanning multiple microscale simulation task (e.g., organ-level processes, cellular dynamics, and subcellular molecular interactions) and evaluation dimensions (e.g., scientific fidelity, visual quality, instruction following). MicroWorldBench reveals that current SOTA video generation models fail in microscale simulation, showing violations of physical laws, temporal inconsistency, and misalignment with expert criteria. To address these limitations, we construct MicroSim-10K, a high-quality, expert-verified simulation dataset. Leveraging this dataset, we train MicroVerse, a video generation model tailored for microscale simulation. MicroVerse can accurately reproduce complex microscale mechanism. Our work first introduce the concept of Micro-World Simulation and present a proof of concept, paving the way for applications in biology, education, and scientific visualization. Our work demonstrates the potential of educational microscale simulations of biological mechanisms. Our data and code are publicly available at https://github.com/FreedomIntelligence/MicroVerse

Detecting and segmenting object instances is a common task in biomedical applications. Examples range from detecting lesions on functional magnetic resonance images, to the detection of tumours in histopathological images and extracting quantitative single-cell information from microscopy imagery, where cell segmentation is a major bottleneck. Attention-based transformers are state-of-the-art in a range of deep learning fields. They have recently been proposed for segmentation tasks where they are beginning to outperforming other methods. We present a novel attention-based cell detection transformer (Cell-DETR) for direct end-to-end instance segmentation. While the segmentation performance is on par with a state-of-the-art instance segmentation method, Cell-DETR is simpler and faster. We showcase the method's contribution in a the typical use case of segmenting yeast in microstructured environments, commonly employed in systems or synthetic biology. For the specific use case, the proposed method surpasses the state-of-the-art tools for semantic segmentation and additionally predicts the individual object instances. The fast and accurate instance segmentation performance increases the experimental information yield for a posteriori data processing and makes online monitoring of experiments and closed-loop optimal experimental design feasible.

Transcriptomic foundation models (TFMs) have recently emerged as powerful tools for analyzing gene expression in cells and tissues, supporting key tasks such as cell-type annotation, batch correction, and perturbation prediction. However, the diversity of model implementations and training strategies across recent TFMs, though promising, makes it challenging to isolate the contribution of individual design choices or evaluate their potential synergies. This hinders the field's ability to converge on best practices and limits the reproducibility of insights across studies. We present BMFM-RNA, an open-source, modular software package that unifies diverse TFM pretraining and fine-tuning objectives within a single framework. Leveraging this capability, we introduce a novel training objective, whole cell expression decoder (WCED), which captures global expression patterns using an autoencoder-like CLS bottleneck representation. In this paper, we describe the framework, supported input representations, and training objectives. We evaluated four model checkpoints pretrained on CELLxGENE using combinations of masked language modeling (MLM), WCED and multitask learning. Using the benchmarking capabilities of BMFM-RNA, we show that WCED-based models achieve performance that matches or exceeds state-of-the-art approaches like scGPT across more than a dozen datasets in both zero-shot and fine-tuning tasks. BMFM-RNA, available as part of the biomed-multi-omics project ( https://github.com/BiomedSciAI/biomed-multi-omic ), offers a reproducible foundation for systematic benchmarking and community-driven exploration of optimal TFM training strategies, enabling the development of more effective tools to leverage the latest advances in AI for understanding cell biology.

To reduce memory costs in long-context inference with Large Language Models (LLMs), many recent works focus on compressing the key-value (KV) cache of different tokens. However, we identify that the previous KV cache compression methods measure token importance individually, neglecting the dependency between different tokens in the real-world language characterics. In light of this, we introduce ChunkKV, grouping the tokens in a chunk as a basic compressing unit, and retaining the most informative semantic chunks while discarding the less important ones. Furthermore, observing that ChunkKV exhibits higher similarity in the preserved indices across different layers, we propose layer-wise index reuse to further reduce computational overhead. We evaluated ChunkKV on cutting-edge long-context benchmarks including LongBench and Needle-In-A-HayStack, as well as the GSM8K and JailbreakV in-context learning benchmark. Our experiments with instruction tuning and multi-step reasoning (O1 and R1) LLMs, achieve up to 10\% performance improvement under aggressive compression ratios compared to existing methods.

Existing works increasingly adopt memory-centric mechanisms to process long contexts in a segment manner, and effective memory management is one of the key capabilities that enables large language models to effectively propagate information across the entire sequence. Therefore, leveraging reward models (RMs) to automatically and reliably evaluate memory quality is critical. In this work, we introduce MemoryRewardBench, the first benchmark to systematically study the ability of RMs to evaluate long-term memory management processes. MemoryRewardBench covers both long-context comprehension and long-form generation tasks, featuring 10 distinct settings with different memory management patterns, with context length ranging from 8K to 128K tokens. Evaluations on 13 cutting-edge RMs indicate a diminishing performance gap between open-source and proprietary models, with newer-generation models consistently outperforming their predecessors regardless of parameter count. We further expose the capabilities and fundamental limitations of current RMs in evaluating LLM memory management across diverse settings.

In this paper, we propose a new class of metric for table structure recognition (TSR) evaluation, called grid table similarity (GriTS). Unlike prior metrics, GriTS evaluates the correctness of a predicted table directly in its natural form as a matrix. To create a similarity measure between matrices, we generalize the two-dimensional largest common substructure (2D-LCS) problem, which is NP-hard, to the 2D most similar substructures (2D-MSS) problem and propose a polynomial-time heuristic for solving it. This algorithm produces both an upper and a lower bound on the true similarity between matrices. We show using evaluation on a large real-world dataset that in practice there is almost no difference between these bounds. We compare GriTS to other metrics and empirically validate that matrix similarity exhibits more desirable behavior than alternatives for TSR performance evaluation. Finally, GriTS unifies all three subtasks of cell topology recognition, cell location recognition, and cell content recognition within the same framework, which simplifies the evaluation and enables more meaningful comparisons across different types of TSR approaches. Code will be released at https://github.com/microsoft/table-transformer.

Agentic language model (LM) systems power modern applications like "Deep Research" and "Claude Code," and leverage multi-LM architectures to overcome context limitations. Beneath their apparent diversity lies a recurring pattern: smaller "compressor" LMs (that can even run locally) distill raw context into compact text that is then consumed by larger "predictor" LMs. Despite their popularity, the design of compressor-predictor systems remains largely ad hoc, with little guidance on how compressor and predictor choices shape downstream performance. In practice, attributing gains to compression versus prediction requires costly, task-specific pairwise sweeps. We argue that these agentic system design questions are, at root, information-theoretic. Viewing the compressor LM as a noisy channel, we introduce a simple estimator of mutual information between the context and its compression to quantify compression quality in a task-independent way. We show that mutual information strongly predicts downstream performance, independent of any specific task. Through an information-theoretic framework, we perform a comprehensive empirical analysis across five datasets and three model families. Results reveal that larger compressors not only are more accurate, but also more token-efficient, conveying more bits of information per token. A 7B Qwen-2.5 compressor, for instance, is 1.6times more accurate, 4.6times more concise, and conveys 5.5times more bits of mutual information per token than its 1.5B sibling. Across datasets, scaling compressors is substantially more effective than scaling predictors, enabling larger on-device compressors to pair with smaller cloud predictors. Applied to a Deep Research system, these principles enable local compressors as small as 3B parameters to recover 99% of frontier-LM accuracy at 26% of API costs.

Nucleus segmentation is a challenging task due to the crowded distribution and blurry boundaries of nuclei. Recent approaches represent nuclei by means of polygons to differentiate between touching and overlapping nuclei and have accordingly achieved promising performance. Each polygon is represented by a set of centroid-to-boundary distances, which are in turn predicted by features of the centroid pixel for a single nucleus. However, using the centroid pixel alone does not provide sufficient contextual information for robust prediction and thus degrades the segmentation accuracy. To handle this problem, we propose a Context-aware Polygon Proposal Network (CPP-Net) for nucleus segmentation. First, we sample a point set rather than one single pixel within each cell for distance prediction. This strategy substantially enhances contextual information and thereby improves the robustness of the prediction. Second, we propose a Confidence-based Weighting Module, which adaptively fuses the predictions from the sampled point set. Third, we introduce a novel Shape-Aware Perceptual (SAP) loss that constrains the shape of the predicted polygons. Here, the SAP loss is based on an additional network that is pre-trained by means of mapping the centroid probability map and the pixel-to-boundary distance maps to a different nucleus representation. Extensive experiments justify the effectiveness of each component in the proposed CPP-Net. Finally, CPP-Net is found to achieve state-of-the-art performance on three publicly available databases, namely DSB2018, BBBC06, and PanNuke. Code of this paper is available at \url{https://github.com/csccsccsccsc/cpp-net

Generative modeling of single-cell RNA-seq data has shown invaluable potential in community-driven tasks such as trajectory inference, batch effect removal and gene expression generation. However, most recent deep models generating synthetic single cells from noise operate on pre-processed continuous gene expression approximations, ignoring the inherently discrete and over-dispersed nature of single-cell data, which limits downstream applications and hinders the incorporation of robust noise models. Moreover, crucial aspects of deep-learning-based synthetic single-cell generation remain underexplored, such as controllable multi-modal and multi-label generation and its role in the performance enhancement of downstream tasks. This work presents Cell Flow for Generation (CFGen), a flow-based conditional generative model for multi-modal single-cell counts, which explicitly accounts for the discrete nature of the data. Our results suggest improved recovery of crucial biological data characteristics while accounting for novel generative tasks such as conditioning on multiple attributes and boosting rare cell type classification via data augmentation. By showcasing CFGen on a diverse set of biological datasets and settings, we provide evidence of its value to the fields of computational biology and deep generative models.

The Non-Local Network (NLNet) presents a pioneering approach for capturing long-range dependencies within an image, via aggregating query-specific global context to each query position. However, through a rigorous empirical analysis, we have found that the global contexts modeled by the non-local network are almost the same for different query positions. In this paper, we take advantage of this finding to create a simplified network based on a query-independent formulation, which maintains the accuracy of NLNet but with significantly less computation. We further replace the one-layer transformation function of the non-local block by a two-layer bottleneck, which further reduces the parameter number considerably. The resulting network element, called the global context (GC) block, effectively models global context in a lightweight manner, allowing it to be applied at multiple layers of a backbone network to form a global context network (GCNet). Experiments show that GCNet generally outperforms NLNet on major benchmarks for various recognition tasks. The code and network configurations are available at https://github.com/xvjiarui/GCNet.

Transformer models struggle with long-context inference due to their quadratic time and linear memory complexity. Recurrent Memory Transformers (RMTs) offer a solution by reducing the asymptotic cost to linear time and constant memory usage. However, their memory update mechanism leads to sequential execution, causing a performance bottleneck. We introduce Diagonal Batching, a scheduling scheme that unlocks parallelism across segments in RMTs while preserving exact recurrence. This approach eliminates the sequential constraint, enabling efficient GPU inference even for single long-context inputs without complex batching and pipelining techniques. Because the technique is purely a run-time computation reordering, existing RMT models adopt it with no retraining. Applied to a LLaMA-1B ARMT model, Diagonal Batching yields a 3.3x speedup over standard full-attention LLaMA-1B and a 1.8x speedup over the sequential RMT implementation on 131,072-token sequences. By removing sequential bottleneck, Diagonal Batching reduces inference cost and latency, thereby strengthening RMTs as a practical solution for real-world, long-context applications.

In biological research, fluorescence staining is a key technique to reveal the locations and morphology of subcellular structures. However, it is slow, expensive, and harmful to cells. In this paper, we model it as a deep learning task termed subcellular structure prediction (SSP), aiming to predict the 3D fluorescent images of multiple subcellular structures from a 3D transmitted-light image. Unfortunately, due to the limitations of current biotechnology, each image is partially labeled in SSP. Besides, naturally, subcellular structures vary considerably in size, which causes the multi-scale issue of SSP. To overcome these challenges, we propose Re-parameterizing Mixture-of-Diverse-Experts (RepMode), a network that dynamically organizes its parameters with task-aware priors to handle specified single-label prediction tasks. In RepMode, the Mixture-of-Diverse-Experts (MoDE) block is designed to learn the generalized parameters for all tasks, and gating re-parameterization (GatRep) is performed to generate the specialized parameters for each task, by which RepMode can maintain a compact practical topology exactly like a plain network, and meanwhile achieves a powerful theoretical topology. Comprehensive experiments show that RepMode can achieve state-of-the-art overall performance in SSP.

Subword tokenization is a common method for vocabulary building in Neural Machine Translation (NMT) models. However, increasingly complex tasks have revealed its disadvantages. First, a vocabulary cannot be modified once it is learned, making it hard to adapt to new words. Second, in multilingual translation, the imbalance in data volumes across different languages spreads to the vocabulary, exacerbating translations involving low-resource languages. While byte-based tokenization addresses these issues, byte-based models struggle with the low information density inherent in UTF-8 byte sequences. Previous works enhance token semantics through local contextualization but fail to select an appropriate contextualizing scope based on the input. Consequently, we propose the Multi-Scale Contextualization (MSC) method, which learns contextualized information of varying scales across different hidden state dimensions. It then leverages the attention module to dynamically integrate the multi-scale contextualized information. Experiments show that MSC significantly outperforms subword-based and other byte-based methods in both multilingual and out-of-domain scenarios. Code can be found in https://github.com/ictnlp/Multiscale-Contextualization.

Unlike autoregressive language models, which terminate variable-length generation upon predicting an End-of-Sequence (EoS) token, Diffusion Language Models (DLMs) operate over a fixed maximum-length context window for a predetermined number of denoising steps. However, this process is independent of the required response length, resulting in computational waste for the majority of short responses common in reasoning and chat tasks. To address this problem, we conjecture that the latent prompt representation contains sufficient information to estimate the required output length. We provide empirical evidence for this phenomenon and propose a zero-shot mechanism to dynamically crop the context window before generation begins, leading to fewer diffusion steps and substantial computational savings. We evaluate our approach on four benchmarks with diverse tasks -- GSM8K (reasoning), HumanEval (code generation), IfEval (instruction following), and LongFormQA (question answering) -- revealing massive efficiency gains at minimal performance impact. We report significant reductions in FLOPs across all tasks, with no statistically significant performance degradation, and significant performance improvements in 2 out of 4 tasks.

Built on the power of LLMs, numerous multimodal large language models (MLLMs) have recently achieved remarkable performance on various vision-language tasks across multiple benchmarks. However, most existing MLLMs and benchmarks primarily focus on single-image input scenarios, leaving the performance of MLLMs when handling realistic multiple images remain underexplored. Although a few benchmarks consider multiple images, their evaluation dimensions and samples are very limited. Therefore, in this paper, we propose a new benchmark MIBench, to comprehensively evaluate fine-grained abilities of MLLMs in multi-image scenarios. Specifically, MIBench categorizes the multi-image abilities into three scenarios: multi-image instruction (MII), multimodal knowledge-seeking (MKS) and multimodal in-context learning (MIC), and constructs 13 tasks with a total of 13K annotated samples. During data construction, for MII and MKS, we extract correct options from manual annotations and create challenging distractors to obtain multiple-choice questions. For MIC, to enable an in-depth evaluation, we set four sub-tasks and transform the original datasets into in-context learning formats. We evaluate several open-source MLLMs and close-source MLLMs on the proposed MIBench. The results reveal that although current models excel in single-image tasks, they exhibit significant shortcomings when faced with multi-image inputs, such as confused fine-grained perception, limited multi-image reasoning, and unstable in-context learning. The annotated data in MIBench is available at https://huggingface.co/datasets/StarBottle/MIBench.

Despite the successes of large language models (LLMs), they exhibit significant drawbacks, particularly when processing long contexts. Their inference cost scales quadratically with respect to sequence length, making it expensive for deployment in some real-world text processing applications, such as retrieval-augmented generation (RAG). Additionally, LLMs also exhibit the "distraction phenomenon," where irrelevant context in the prompt degrades output quality. To address these drawbacks, we propose a novel RAG prompting methodology, superposition prompting, which can be directly applied to pre-trained transformer-based LLMs without the need for fine-tuning. At a high level, superposition prompting allows the LLM to process input documents in parallel prompt paths, discarding paths once they are deemed irrelevant. We demonstrate the capability of our method to simultaneously enhance time efficiency across a variety of question-answering benchmarks using multiple pre-trained LLMs. Furthermore, our technique significantly improves accuracy when the retrieved context is large relative the context the model was trained on. For example, our approach facilitates an 93x reduction in compute time while improving accuracy by 43\% on the NaturalQuestions-Open dataset with the MPT-7B instruction-tuned model over naive RAG.

Modern Large Language Models (LLMs) are increasingly trained to support very large context windows. We present Compactor, a training-free, query-agnostic KV compression strategy that uses approximate leverage scores to determine token importance. We show that Compactor can achieve the same performance as competing methods while retaining 20% fewer tokens in both synthetic and real-world context tasks, while being more task-robust. We further introduce a procedure for context-calibrated compression: inferring the maximum compression a given context supports before significant performance loss. Using context-calibrated compression, we show that Compactor achieves full KV performance on Longbench while reducing the KV memory burden by 68%, on average. To demonstrate the efficacy and generalizability of our approach, we apply Compactor to 27 synthetic and real-world tasks from RULER and Longbench, with models from both the Qwen 2.5 and Llama 3.1 families. Finally, we release compactor-vllm, an inference engine and suite of optimized Triton kernels designed to efficiently support the sparse, non-contiguous memory access patterns inherent to compressed KV caches. This work demonstrates that Compactor offers a practical, high-performance solution for alleviating the memory bottleneck in modern LLM deployment.

As large language models engage in extended reasoning tasks, they accumulate significant state -- architectural mappings, trade-off decisions, codebase conventions -- within the context window. This understanding is lost when sessions reach context limits and undergo lossy compaction. We propose Contextual Memory Virtualisation (CMV), a system that treats accumulated LLM understanding as version-controlled state. Borrowing from operating system virtual memory, CMV models session history as a Directed Acyclic Graph (DAG) with formally defined snapshot, branch, and trim primitives that enable context reuse across independent parallel sessions. We introduce a three-pass structurally lossless trimming algorithm that preserves every user message and assistant response verbatim while reducing token counts by a mean of 20% and up to 86% for sessions with significant overhead by stripping mechanical bloat such as raw tool outputs, base64 images, and metadata. A single-user case-study evaluation across 76 real-world coding sessions demonstrates that trimming remains economically viable under prompt caching, with the strongest gains in mixed tool-use sessions, which average 39% reduction and reach break-even within 10 turns. A reference implementation is available at https://github.com/CosmoNaught/claude-code-cmv.

What data should a vision-language model be trained on? To answer this question, many data curation efforts center on the quality of a dataset. However, most of these existing methods are (i) offline, i.e. they produce a static dataset from a set of predetermined filtering criteria, and (ii) concept-agnostic, i.e. they use model-based filters which induce additional data biases. In this work, we go beyond such offline, concept-agnostic methods and advocate for more flexible, task-adaptive online concept-based curation. Our first contribution is DataConcept, a collection of 128M web-crawled image-text pairs annotated with fine-grained details about their concept composition. Building on DataConcept, we introduce Concept-Aware Batch Sampling (CABS), a simple yet effective batch sampling framework that flexibly constructs batches on-the-fly based on specific target distributions. We propose two variants: (i) Diversity Maximization (CABS-DM) to curate batches with a broad coverage of available concepts, and (ii) Frequency Maximization (CABS-FM) to curate batches with high object multiplicity. Through extensive evaluations across 28 benchmarks, we demonstrate that our CABS method significantly benefits CLIP/SigLIP model classes and yields highly performant models. Overall, CABS represents a strong open-source alternative to proprietary online data curation algorithms, enabling practitioners to define custom concept distributions that optimize for specific downstream tasks.

State Space Models (SSMs) have recently emerged as efficient alternatives to Transformer-Based Models (TBMs) for long-sequence processing, offering linear scaling and lower memory use. Yet, how contextual information flows across layers and tokens in these architectures remains understudied. We present the first unified, token- and layer-level analysis of representation propagation in SSMs and TBMs. Using centered kernel alignment, stability metrics, and probing, we characterize how representations evolve within and across layers. We find a key divergence: TBMs rapidly homogenize token representations, with diversity reemerging only in later layers, while SSMs preserve token uniqueness early but converge to homogenization deeper. Theoretical analysis and parameter randomization further reveal that oversmoothing in TBMs stems from architectural design, whereas in SSMs it arises mainly from training dynamics. These insights clarify the inductive biases of both architectures and inform future model and training designs for long-context reasoning.