Single-cell RNA-seq (scRNA-seq) enables atlas-scale profiling of complex tissues, revealing rare lineages and transient states. Yet, assigning biologically valid cell identities remains a bottleneck because markers are tissue- and state-dependent, and novel states lack references. We present CellMaster, an AI agent that mimics expert practice for zero-shot cell-type annotation. Unlike existing automated tools, CellMaster leverages LLM-encoded knowledge (e.g., GPT-4o) to perform on-the-fly annotation with interpretable rationales, without pre-training or fixed marker databases. Across 9 datasets spanning 8 tissues, CellMaster improved accuracy by 7.1
Unified multimodal models can both understand and generate visual content within a single architecture. Existing models, however, remain data-hungry and too heavy for deployment on edge devices. We present Mobile-O, a compact vision-language-diffusion model that brings unified multimodal intelligence to a mobile device. Its core module, the Mobile Conditioning Projector (MCP), fuses vision-language features with a diffusion generator using depthwise-separable convolutions and layerwise alignment. This design enables efficient cross-modal conditioning with minimal computational cost. Trained on only a few million samples and post-trained in a novel quadruplet format (generation prompt, image, question, answer), Mobile-O jointly enhances both visual understanding and generation capabilities. Despite its efficiency, Mobile-O attains competitive or superior performance compared to other unified models, achieving 74
Playing video games requires perception, reasoning, memory, and long-horizon planning—exactly the faculties expected of modern large language and vision–language models (LLMs/VLMs). We introduce LMGame-Bench, a benchmark built on six popular games spanning platformer, puzzle, and narrative games through a unified Gym‑style API. Unlike prior game benchmarks that entangle multiple skills, LMGame-Bench employs a modular harness—including perception, memory, and reasoning modules—that can be toggled to selectively probe distinct capabilities. The benchmark further improves robustness through prompt standardization and contamination mitigation. Evaluation of 13 state-of-the-art models demonstrates that LMGame-Bench remains challenging yet effectively discriminates among models. Correlation analysis reveals that individual games align with core LLM capabilities, providing a quantitative framework for interpreting performance. Finally, LMGame-Bench exposes models’ limitations in visual state extraction, reflection, spatiotemporal reasoning, and long-context reasoning, pointing to concrete directions for model improvement.
Diffusion-based language models offer a compelling alternative to autoregressive (AR) models by enabling parallel and controllable generation. Among this family of models, Masked Diffusion Models (MDMs) achieve the strongest performance but still underperform AR models in perplexity and lack key inference-time efficiency features--most notably, KV caching. In this work, we introduce Eso-LMs, a new family of models that fuses AR and MDM paradigms, enabling smooth interpolation between their perplexities while overcoming their respective limitations. Eso-LMs set a new state of the art on standard language modeling benchmarks. Crucially, we are the **first to introduce KV caching for MDMs** while preserving parallel generation, significantly improving inference efficiency. Combined with an optimized sampling schedule, our method achieves up to **65x** faster inference than standard MDMs and **4x** faster inference than prior semi-autoregressive approaches. We provide the code and model checkpoints on the project page: [http://s-sahoo.github.io/Eso-LMs](this http URL)
End-to-end automation of realistic healthcare operations stresses three capabilities underrepresented in current benchmarks: policy density, decisions must be grounded in a large library of medical, insurance, and operational rules; Multi-role composition: a single task requires the agent to play multiple roles with handoffs; and multilateral interaction: intermediate workflow steps are multi-turn dialogs, such as peer-to-peer review and patient outreach. We introduce χ-Bench, a benchmark of long-horizon healthcare workflows across three domains: provider prior authorization, payer utilization management, and care management. Each task hands the agent a clinical case in a high-fidelity simulator of 20 healthcare apps exposed via 87 MCP tools, which it must drive to a terminal status through tool calls and writing the role's artifacts, guided by a 1,290+ document managed-care operations handbook skill. Across 30 agent harness/models configurations, the best agent resolves only 28.0
Training large language models requires jointly configuring two interdependent aspects of the system: the global batch size, which governs statistical efficiency, and the 3D parallelism strategy, which governs hardware throughput. Existing approaches make these decisions independently: optimization work adapts the batch size to track the evolving critical batch size while keeping parallelism fixed, and systems work selects the fastest parallelism for a given fixed batch size without anticipating that the optimal batch size could change. We show that these decisions are tightly coupled: the throughput-optimal parallelism strategy may shift as the global batch size changes, so any method that fixes one while adapting the other operates with a suboptimal configuration for part of the training run. We present COPUS, a system that adaptively tunes the global batch size, parallelism strategy, and micro-batch size as training evolves. COPUS is guided by Goodput, the product of throughput and statistical efficiency, which models both hardware and statistical effects jointly and directly measures useful convergence per unit of wall-clock time. The system combines online gradient noise scale estimation under 3D parallelism with throughput-aware evaluation of candidate configurations, and supports efficient reconfiguration of both batch size and parallelism during training. We evaluate COPUS on LLM pre-training workloads across 1-4 nodes of 8xH100 and 8xMI210 GPUs and model sizes from 3B to 32B parameters, demonstrating average time-to-convergence speedups of 3.9-8.0
How should an agent decide when and how to plan? A dominant approach builds agents as reactive policies with adaptive computation (e.g., chain-of-thought), trained end-to-end expecting planning to emerge implicitly. Without control over the presence, structure, or horizon of planning, these systems dramatically increase reasoning length, yielding inefficient token use without reliable accuracy gains. We argue efficient agentic reasoning benefits from decomposing decision-making into three systems: simulative reasoning (System II) grounding deliberation in future-state prediction via a world model; self-regulation (System III) deciding when and how deeply to plan via a learned configurator; and reactive execution (System I) handling fine-grained action. Simulative reasoning provides unified planning across diverse tasks without per-domain engineering, while self-regulation ensures the planner is invoked only when needed. To test this, we develop SR^2AM (Self-Regulated Simulative Reasoning Agentic LLM), realizing both as distinct stages within an LLM's chain-of-thought, with the LLM as world model. We explore two instantiations: recording decisions from a prompted multi-module system (v0.1) and reconstructing structured plans from traces of pretrained reasoning LLMs (v1.0), trained via supervised then reinforcement learning (RL). Across math, science, tabular analysis, and web information seeking, v0.1-8B and v1.0-30B achieve Pass@1 competitive with 120-355B and 685B-1T parameter systems respectively, while v1.0-30B uses 25.8-95.3
What is an agent? What constitutes agency? With the rise of Large Language Model (LLM) systems marketed as “coding agents”, “AI co-scientists”, and other “agentic" tools that promise to drive up productivity, and at the same time, “existential" concerns such as AI escaping human control with destructive power under a speculative “machine agency" against humans, it has become essential to clarify where automation ends and agency begins, both for building capable systems and for understanding whether and what to fear. Drawing on Descartes' grounding of agency in independent thought, and on portrayals of autonomous beings in science fiction, we survey the current landscape of AI agents, and analyze agent architectures along five dimensions: goal, identity, decision-making, self-regulation, and learning. Specifically, we argue that genuine agency requires these structures to be internalized within the system itself rather than assembled through external scaffolding. This distinction between agentic systems, whose competence resides in engineered workflows, and agentive systems, whose capabilities (including social interaction) arise endogenously, defines the boundary between systems designed for prescribed tasks, and those capable of operating in the open world with true autonomy. Building on this analysis, we propose the Goal-Identity-Configurator (GIC) architecture for a general-purpose agent model, combining hierarchical goal decomposition, identity evolution, simulative reasoning grounded in a separately trained world model, learned self-regulation, and self-directed learning from both real and simulated experience. Furthermore, we share insight on the auditability, controllability, and safety of agentive systems that possess greater autonomy and “agency", but remain under human oversight.
The attention mechanism in Transformers is an important primitive for accurate and scalable sequence modeling. Its quadratic-compute and linear-memory complexity however remain significant bottlenecks. Linear attention and state-space models enable linear-time, constant-memory sequence modeling and can moreover be trained efficiently through matmul-rich parallelization across sequence length. However, at their core these models are still RNNs, and thus their use of a fixed-size hidden state to model the context is a fundamental limitation. This paper develops log-linear attention, an attention mechanism that balances linear attention's efficiency and the expressiveness of softmax attention. Log-linear attention replaces the fixed-size hidden state with a logarithmically growing set of hidden states. We show that with a particular growth function, log-linear attention admits a similarly matmul-rich parallel form whose compute cost is log-linear in sequence length. Log-linear attention is a general framework and can be applied on top of existing linear attention variants. As case studies, we instantiate log-linear variants of two recent architectures -- Mamba-2 and Gated DeltaNet -- and find they perform well compared to their linear-time variants.
LLM agents now perform strongly in software engineering, deep research, GUI automation, and various other applications, while recent agent scaffolds and models are increasingly integrating these capabilities into unified systems. Yet, most evaluations still test these capabilities in isolation, which leaves a gap for more diverse use cases that require agents to combine different capabilities. We introduce CocoaBench, a benchmark for unified digital agents built from human-designed, long-horizon tasks that require flexible composition of vision, search, and coding. Tasks are specified only by an instruction and an automatic evaluation function over the final output, enabling reliable and scalable evaluation across diverse agent infrastructures. We also present CocoaAgent, a lightweight shared scaffold for controlled comparison across model backbones. Experiments show that current agents remain far from reliable on CocoaBench, with the best evaluated system achieving only 45.1
Predicting cellular responses to genetic or chemical perturbations has been a long-standing goal in biology. Recent applications of foundation models to this task have yielded contradictory results regarding their superiority over simple baselines. We conducted an extensive analysis of over 600 different models across various prediction tasks and evaluation metrics, demonstrating that while some foundation models fail to outperform simple baselines, others significantly improve predictions for both genetic and chemical perturbations. Furthermore, we developed and evaluated methods for integrating multiple foundation models for perturbation prediction. Our results show that with sufficient data, these models approach fundamental performance limits, confirming that foundation models can improve cellular response simulations. Code and Data: https://github.com/genbio-ai/foundation-models-perturbation
Long-context recall in linear-time sequence models highlights a tradeoff in how they write to memory. State-based linear models, such as state-space models (SSMs) and linear Transformers, write densely, updating the entire state for each newly arrived token, which leads to interference and makes specific past tokens hard to recover. Sliding-window attention (SWA) exhibits the opposite behavior: it writes sparsely by storing explicit token representations, but only within a fixed window, so recall drops once the relevant token is evicted. Interpolating between these models, we introduce Raven, a linear-time sequence model that maintains a fixed set of memory slots and, at each step, decays and updates only a selected subset via learned, input-dependent routing. This lets Raven mitigate SWA's position-based overwriting and hard eviction while reducing interference from dense state updates in SSMs, thereby preserving long-range content much more effectively. Across recall-intensive benchmarks, Raven is competitive with or outperforms prior linear-time baselines, achieving strong long-context recall where both SWA and SSMs sharply degrade. It remains effective when extrapolating to context lengths as large as 16x its training length, with similar gains in hybrid architectures.
LAPS identifies and disaggregates requests with different prompt lengths in LLM serving to reduce TTFT latency. While recent systems have decoupled the prefill and decode stages to improve throughput, they still rely on unified scheduling policies that fail to adapt to heterogeneous workload characteristics. We observe that prompt-length variations lead to distinct performance bottlenecks, motivating an adaptive scheduling strategy. LAPS disaggregates multi-turn long-prefill requests from short-prefill ones and introduces a length-aware smart batching mechanism for short-prefill workloads. It adopts a dual-queue design that supports temporal disaggregation on a single prefill instance or spatial disaggregation across multiple instances. For short-prefill batches, a batch waiting window and CUDA Graph-based clustering mitigate interference from heterogeneous computation, reducing batching delay and lowering average latency. In real multi-turn workloads, LAPS reduces prefill latency by over 30% compared to vanilla SGLang under prefill-decode disaggregation, and further decreases SLO violations by 28% in multi-instance deployments with vanilla data-parallel configuration. Compared to the SGLang router with load balancing, it further lowers SLO violations by 12% in multi-GPU settings. Under high concurrency and mixed-request scenarios, LAPS improves request throughput by 35% serving Qwen2.5-32B model for prefill instance, demonstrating its effectiveness in optimizing heterogeneous LLM serving workloads.
Motivation Single-cell foundation models (FMs) pretrained on massive unlabeled scRNA-seq data show strong potential in predicting transcriptional responses to unseen genetic perturbations (e.g. knockouts, variants). However, existing approaches do not effectively transfer pretrained knowledge and overlook the imbalance between perturbation-sensitive and insensitive genes, yielding only marginal improvements over non-pretrained baselines.Results To address these limitations, we introduce PertAdapt, a framework that unlocks FMs to accurately predict genetic perturbation effects by integrating a plug-in perturbation adapter and an adaptive loss. The adapter employs a gene-similarity-masked attention mechanism to jointly encode perturbation conditions and contextualized representations of unperturbed cells, enabling more effective knowledge transfer. To better capture differential expression patterns, the adaptive loss dynamically reweights perturbation-sensitive genes relative to global transcriptomic signals. Extensive experiments across seven perturbation datasets, including both single- and double-gene settings, demonstrate that PertAdapt consistently outperforms non-pretrained and FM baselines. Moreover, PertAdapt demonstrates strong capacity to model multiplexed gene interactions, to generalize in limited-data regimes, and to maintain robustness across backbone sizes.Availability and implementation Code is available at https://github.com/BaiDing1234/PertAdapt.
We introduce Retrieval-Augmented Interpretable Learning (RAIL), a probabilistic meta-learning framework for zero-shot generation of task-specific interpretable models that synthesizes coefficient-space structure from natural-language task descriptions and a memory of previously learned task-specific predictors. RAIL retrieves related source tasks, transfers structure through coefficient space, and generates a new predictor in the original diagnostic-feature space, enabling zero-shot and few-shot clinical procedure prediction with feature-level explanations. Its probabilistic formulation provides uncertainty over retrieval, model coefficients, and predictions, supporting reliability-aware deployment: uncertain predictions or unstable explanations can be flagged for additional clinical review rather than treated as automatic decisions. This makes RAIL particularly suited for healthcare settings, where prediction tasks are highly long-tailed, new clinical targets arise frequently, and models must remain inspectable, uncertainty-aware, and compatible with human oversight. Across long-tailed clinical procedure prediction tasks, RAIL maintains reliable performance across data-availability regimes: it achieves 73.4
Recent vision-language models (VLMs) show strong reasoning capabilities through training with reinforcement learning from verifiable rewards (RLVR). Despite their impressive capabilities, current VLMs focus on a limited range of reasoning tasks, such as mathematical and logical reasoning, due to the lack of readily available verifiable reward data in broader domains. As a result, these models struggle to generalize their reasoning abilities to the wide variety of challenges encountered in real-world environments. To address this limitation, we collect and assemble a comprehensive RL-ready visual reasoning training dataset encompassing 46 datasets across 13 dimensions of 5 domains, covering a wide range of realistic scenarios such as infographic reasoning, mathematical reasoning, spatial reasoning, and general science reasoning. Based on this dataset, we propose an influence function-based data filtering strategy and a multi-round data curriculum method to iteratively strengthen general visual reasoning abilities. Using this approach, we train a general reasoning VLM, namely Vision-G1. Our 7B model achieves state-of-the-art performance across nine visual reasoning benchmarks, surpassing previous similar-sized VLMs and even GPT-4o and Gemini-1.5 Flash.
Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local structural constraints. Existing deep learning approaches achieve strong recovery rates, however, lack explicit mechanisms to reuse fine-grained structure-sequence patterns conserved across natural proteins. To mitigate this, we present PRISM a multimodal retrieval-augmented generation framework for inverse folding. PRISM retrieves fine-grained representations of potential motifs from known proteins and integrates them with a hybrid self-cross attention decoder. PRISM is formulated as a latent-variable probabilistic model and implemented with an efficient approximation, combining theoretical grounding with practical scalability. Experiments across multiple benchmarks, including CATH-4.2, TS50, TS500, CAMEO 2022, and the PDB date split, demonstrate the fine-grained multimodal retrieval efficacy of PRISM in yielding SoTA perplexity and amino acid recovery, while also improving the foldability metrics (RMSD, TM-score, pLDDT).
Modern predictive systems are expected to adapt their behavior to the specific situation they are facing. A clinical model should not treat every patient the same; a retrieval-augmented model should change its answer when given different evidence; a mixture-of-experts model should route different inputs to different experts. We call this capability context-adaptive inference: before predicting, the system uses information about the current context to specialize its parameters or computation for that instance. This article provides a unified view of context-adaptive inference across three traditions that are usually treated separately: (i) explicit adaptation in statistics (e.g. varying-coefficient models, local regression, hierarchical sharing), (ii) rapid task-specific adaptation in meta-learning and transfer, and (iii) implicit adaptation in large foundation models via prompting, retrieval, and expert routing. We formalize these approaches under a common objective: to map context $c$ to adapted parameters $θ(c)$, then to predict via $f(x; θ(c))$. Under squared loss, linear prediction heads, and fixed features, we prove that explicit parameter adaptation and implicit routing are mathematically equivalent to kernel ridge regression on joint features of inputs and context. Building on this bridge, we propose practical design principles and evaluation metrics including adaptation-efficiency, routing stability, and context-specific robustness to guide when to specialize, how to constrain that specialization, and how to audit context-adaptive models in deployment. Finally, we identify open problems in identifiability, robustness under distribution shift, and efficient large-scale adaptation, outlining design principles for methods that are scalable, reliable, and transparent in real-world settings.
Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of cellular heterogeneity by providing gene expression data at single-cell resolution, uncovering insights into rare cell populations, cell-cell interactions, and gene regulation. Foundation models pretrained on large-scale scRNA-seq datasets have shown great promise in analyzing such data, but existing approaches are often limited to modeling a small subset of highly expressed genes and lack the integration of external gene-specific knowledge. To address these limitations, we present scLong, a billion-parameter foundation model pretrained on 48 million cells. scLong performs self-attention across the entire set of 28,000 genes in the human genome. This enables the model to capture long-range dependencies between all genes, including lowly expressed ones (containing unexpressed genes with zero expressions), which often play critical roles in cellular processes but are typically excluded by existing foundation models. Additionally, scLong integrates gene knowledge from the Gene Ontology using a graph convolutional network, enriching its contextual understanding of gene functions and relationships. In extensive evaluations, scLong surpasses both state-of-the-art scRNA-seq foundation models and task-specific models across diverse tasks, including predicting transcriptional responses to genetic and chemical perturbations, forecasting cancer drug responses, and inferring gene regulatory networks.
State-space models (SSMs) offer efficient sequence modeling but show a large performance gap compared to Transformers on benchmarks that require in-context retrieval. This gap has been linked to a small set of attention heads, called Gather-and-Aggregate (G&A), which SSMs struggle to implement and are believed to drive the disparity. Leveraging this insight, we propose retrieval-aware distillation, a strategy that converts a pretrained Transformer into a hybrid student by preserving only these retrieval-critical components. We identify essential attention heads via ablation on a synthetic retrieval task and distill the rest into recurrent heads, resulting in a model with non-uniform attention placement tailored to retrieval demands. We empirically show that preserving just 2% of attention heads enables the hybrid model to recover teacher-level performance (10 retrieval-critical heads in a 1B model), reducing memory overhead by up to 6x compared to prior distillation methods that retain 30–50% of heads. Furthermore, we show that large recurrent states in SSMs often compensate for missing retrieval. Once retrieval is handled by these specific heads, the SSM backbone can be significantly simplified while maintaining performance, even with an 8x reduction in state dimension. Overall, the results show that strategically concentrating attention can close the Transformer–SSM gap with a fraction of the memory cost.