arXiv subjects

Junzhou Huang

Publications and source records attributed to Junzhou Huang.

At least 19 recordsLinked to original sources

arXiv2026

CytoWave: Perturbation-Centric Pretraining for Single-Cell Response Prediction

Predicting gene expression under perturbations from single-cell data is a fundamental task for modeling cellular responses, with applications in discovering gene function and designing therapeutics. However, existing methods often struggle to generalize across datasets due to differences in experimental protocols, biological contexts, and species. We present \textbf{CytoWave}, a perturbation-centric pretraining framework for single-cell genetic perturbation response prediction. We leverage large-scale cross-species perturbation datasets unified via orthology and train CytoWave in a two-stage manner. In the first stage, we learn reference control cell states via masked gene expression recovery on unperturbed cells. In the second stage, we pretrain the model to predict perturbed gene expression given control states and perturbation signals, together with a contrastive objective that aligns latent representations of perturbation responses with perturbation signals. We perform strict dataset-held-out evaluation across multiple condition combinations and case studies of pathway activity changes, demonstrating consistent and effective performance of CytoWave in predicting single-cell genetic perturbation responses.

cs.LG↗

arXiv2026

Training Autoregressive Language Models on Rounded, Bounded, and Censored Numerical Labels via Exact Likelihood

Numerical labels often specify a set of possible values: a measurement is rounded, a laboratory test reports only a bound, or a program is stopped at a timeout. We introduce boundary marginalization, the first method that trains an autoregressive language model on the exact likelihood of such observations through its existing digit tokens. A fixed-width, order-preserving numeral representation groups consecutive grid values under shared digit prefixes. An interval is a union of such groups, so its exact probability and gradient follow from at most two boundary paths, the successive digit prefixes of its endpoints, each of length logarithmic in the number of grid values. The resulting objective unifies precise, rounded, bounded, and censored supervision and trains digit decisions at the resolution supplied by each observation. The same computation supports exact distributional queries and unbiased gradients for the continuous ranked probability score on exact labels. Experiments show recovery of a conditional distribution from rounded and censored reports alone, improved likelihood on naturally censored molecular measurements, and more accurate code latency distributions on two backbones. Exact interval updates remain tractable as the numerical support grows to one million values.

cs.LG↗

arXiv2026

B2P-Corr: Batch-to-Population Gradient Estimators for Non-Decomposable Correlation Losses

Correlation metrics such as the Pearson Correlation Coefficient (PCC) and Concordance Correlation Coefficient (CCC) are standard regression metrics and learning objectives, but their non-decomposable nature poses a challenge for stochastic optimization. Since these metrics depend on dataset-level moments (mean, variance, covariance), naive mini-batch training with local statistics yields biased, high-variance gradients whose expectation does not align with the population gradient. To bridge this ``batch-to-population'' (B2P) gap, we propose B2P-Corr, a novel framework that transforms correlation objectives into decomposable pseudo-losses driven by lightweight global ``moment sketches''. We introduce two efficient variants: B2P-EMA, which utilizes exponential moving averages and stop-gradient operators to ensure asymptotic gradient tracking with $O(B)$ cost ($B$ is batch size); and B2P-U, which uses sampled cross-batch U-statistic estimators and a reservoir-based stabilization with an $O(B)$ implementation. Theoretically, we quantify the $O(B^{-1})$ bias of naive mini-batch optimization, prove a moving-target tracking result for B2P-EMA under a fast-sketch / slow-parameter regime, and provide an idealized control-variate analysis for B2P-U. Experiments on two synthetic and three real-world datasets demonstrate B2P-Corr achieves stable optimization and higher correlation than naive mini-batch optimization with negligible overhead.

cs.LG↗

arXiv2026

HiSTOR: Structured Treatment-outcome Representation Learning for High-Dimensional Longitudinal Data

Estimating potential outcomes under alternative treatment sequences is essential for personalized decision-making, but remains challenging with high-dimensional covariates and time-varying confounding. In this study, we propose HiSTOR (High-dimensional Structured Treatment-Outcome Representation), an end-to-end framework that integrates nonlinear dimension reduction with longitudinal counterfactual prediction. The central idea is to learn structured low-dimensional representations of both current patient states and evolving histories, according to their shared and distinct relationships with treatment assignment and outcomes. This extends latent-space covariate adjustment to longitudinal settings, jointly addressing covariate dimensionality and historical complexity. The resulting framework supports one-step and multi-step outcome prediction under specified treatment sequences. Experiments on CVSim and CancerSim demonstrate the superiority of HiSTOR across varying covariate dimensions, confounding strengths, and prediction horizons compared to state-of-the-art methods. To sum up, HiSTOR offers a unified approach to connecting high-dimensional covariate adjustment with longitudinal potential-outcome prediction.

cs.LG↗

arXiv2026

VCLMU: Mechanism-Centric Virtual Cell World Modeling for Perturbation Response

Predicting cellular responses to genetic perturbations is a central capability for virtual cells and a key step toward computational modeling of biological interventions. Most existing models directly map an unperturbed molecular profile and perturba- tion to the resulting observation without explicitly representing the latent cellular transition induced by the intervention. We introduce a mechanism-centric virtual cell world model that represents cellular state as a set of Latent Mechanism Units (LMUs) and treats genetic perturbations as actions on these latent states. Each LMU combines a reusable identity grounded in multimodal biological evidence with an observation-specific state, allowing a perturbation to induce mechanism- specific stochastic transitions before decoding the resulting transcriptional response. We train VCLMU through two-stage pretraining, first on around 200K pseudo-bulk perturbation profiles and then on gene-aligned single-cell perturbation data. Across six perturbation-disjoint benchmarks, VCLMU consistently improves perturbation- specific response recovery over strong baselines while maintaining competitive global response accuracy. We further analyze learned LMUs through enrichment between perturbation responses and LMU gene sets and show that they capture structured biological response programs. These results support mechanism-level latent state transition as a useful formulation for virtual cell models that aim to predict and interpret cellular responses to biological interventions.

cs.AI↗

arXiv2026

Who Holds the Pen? Let Specifications, Not Agents, Sign Off

Large language model agents increasingly combine generation, decision-making, execution, and self-evaluation within a single agentic loop. Although they operate under external specifications such as task instructions, guidelines, output schemas, and reusable skills, these specifications typically remain context for the same model that acts and declares completion, leaving no independent specification authority boundary. We identify two resulting gaps. The understanding--execution gap arises when a requirement is understood but not satisfied in execution; the state--authority gap arises when an agent's interpretation or completion claim does not establish the required state. On SkillsBench, using only agent-visible prompts, workspace information, and injected skill specifications, we extract 509 source-grounded task directions. Across seven models, only 79.6%--86.4% are satisfied, while completion-claim rates exceed official evaluator pass rates by 28.7--37.9 percentage points. We therefore separate agent proposals from authoritative state. Agents may plan, act, and request completion, but only admissible evidence from qualified providers may establish specification-governed state. SpecHarness operationalizes this principle by compiling visible specifications into source-linked obligations and governing execution and finalization through versioned obligation state. Verifiable requirements are mediated or validated at runtime, while ambiguous or subjective requirements remain advisory. Experiments on guideline-following and artifact-generation tasks show that specifications can serve not merely as behavioral guidance, but as authority over compliant execution and completion.

cs.AI↗

arXiv2026

Learning A Unified Template for Gait Recognition

"What I cannot create, I do not understand."Human wisdom reveals that creation is one of the highest forms of learning. For example, Diffusion Models have demonstrated remarkable semantic structure and memory in image generation, understanding, and restoration, which intuitively benefits representation learning. However, current gait networks rarely embrace this perspective, relying primarily on learning by contrasting gait samples under varying complex conditions, leading to semantic inconsistency and uniformity issues. To address these issues, we propose Origins with generative capabilities whose underlying philosophy is that different entities are generated from a unified template, inherently regularizing gait representations within a consistent and diverse semantic space to capture accurate gait differences. Admittedly, learning this unified template is exceedingly challenging, as it requires the comprehensiveness of the template to encompass gait representations with various conditions. Inspired by Diffusion Models, Origins diffuses the unified template into timestep templates for gait generative learning, and meanwhile transfers the unified template for gait representation learning. Especially, gait generative and representation learning serve as a unified framework for end-to-end joint training. Extensive experiments on CASIA-B, CCPG,SUSTech1K, Gait3D, GREW and CCGR-MINI demonstrate that Origins performs unified generative and representation learning, achieving superior performance.

cs.CV↗

arXiv2026

Rendering-Aware Bayesian 3D Gaussian Splatting with Native Uncertainty and Adaptive Complexity Control

3D Gaussian splatting (3DGS) is a strong representation for real-time novel-view synthesis, but its standard training pipeline relies on point estimates and hand-tuned heuristics, providing no native uncertainty or principled complexity control. This is most limiting under sparse views or fixed acquisition budgets, where a model must identify weakly supported geometry and select informative views. We introduce a rendering-aware Bayesian 3DGS framework that tracks Gaussian geometry with a Normal-Inverse-Wishart posterior over means and covariances using renderer-derived surrogate summaries. An optional Dirichlet-process extension adds a probabilistic component-usage signal, and the training schedule makes the closed-form versus approximate inference boundary explicit. Re-rendering posterior geometry samples yields native predictive uncertainty for interval calibration and active view selection. In a fixed-budget 16-to-32 active-view task, native NIW acquisition improves PSNR by +0.453 dB and LPIPS by -0.0146 over a scoring-only 3-member standard-ensemble baseline, winning 29/39 scene-seed pairs and 10/13 scene means; it also improves over PPU-style (+0.355 dB) and NIW-proxy (+0.401 dB) acquisition. NIW native intervals reduce 95% coverage error by about 17x relative to a shared proxy (0.046 vs. 0.796) and are about 10x closer to nominal coverage than a 3-member deep ensemble (0.047 vs. 0.454) at roughly one-third the training cost. As a reconstruction compatibility check, paired NIW-vs-standard analysis over 39 scene-seed runs yields +0.030 dB PSNR with 1.6% additional training time. These results position Bayesian 3DGS as a practical probabilistic scene representation for decision-facing tasks such as active view selection.

cs.CV↗

arXiv2026

Histopathology Multi-modal Embedding for Pathology Composed Retrieval

To overcome the black-box nature of predictive AI and the hallucination risks of generative models, retrieval-based models offer an interpretable, evidence-based paradigm for pathology clinical workflow. However, real-world clinical queries are inherently interleaved (e.g., pathology images and text). Current dual-encoders suffer from an \textbf{Architectural Mismatch}, lacking the mechanism to fuse such composed queries. To address this, we formalize the task of Pathology Composed Retrieval (PCR). While Multimodal Large Language Models (MLLMs) offer deep-fusion capabilities, directly applying them exposes a \textbf{Task Mismatch} and a \textbf{Domain Mismatch}. To resolve these challenges, we propose HOMIE, a model-agnostic adaptation framework that transforms any generative MLLM into a specialized pathology retrieval expert. Evaluated on our newly introduced PCR Benchmark, a lightweight 2B-parameter HOMIE variant substantially outperforms existing paradigms, surpassing specialized 7B pathology MLLMs and dual-encoders by large margins on composed retrieval, while maintaining strong performance on traditional simple retrieval. The project page is available at https://qfchou.github.io/HOMIE_page/.

cs.CV↗

arXiv2026

Universal Guideline-Driven Image Clustering via a Hybrid LLM Agent

Unifying image clustering across different clustering scenarios remains challenging due to fundamental gaps among tasks. We introduce a Guideline-Driven Image Clustering Agent, the first universal framework that bridges these gaps through textual guidelines. To incorporate complex guidelines without task-specific training, we propose Generative Concept Proxy Modeling, which generates guideline-aware embeddings via concept proxy extraction. For scenarios requiring automatic cluster discovery, we introduce LLM Traversal based on Minimum Spanning Tree that selectively applies LLM reasoning for complex semantic judgments. Our method generalizes across diverse clustering scenarios spanning from general to fine-grained categorization, from global to local criteria, and from balanced to long-tail distributions. Our framework consistently outperforms specialized methods across diverse clustering tasks.

cs.CV↗

arXiv2026

scpFormer: A Foundation Model for Unified Representation and Integration of the Single-Cell Proteomics

The integration of single-cell proteomic data is often hindered by the fragmented nature of targeted antibody panels. To address this limitation, we introduce scpFormer, a transformer-based foundation model designed for single-cell proteomics. Pre-trained on over 390 million cells, scpFormer replaces standard index-based tokenization with a continuous, sequence-anchored approach. By combining Evolutionary Scale Modeling (ESM) with value-aware expression embeddings, it dynamically maps variable panels into a shared semantic space without artificial discretization. We demonstrate that scpFormer generates global cell representations that perform competitively in large-scale batch integration and unsupervised clustering. Moreover, its open-vocabulary architecture facilitates in silico panel expansion, assisting in the reconstruction of biological manifolds in sparse clinical datasets. Finally, this learned protein co-expression logic is transferable to bulk-omics tasks, supporting applications like cancer drug response prediction. scpFormer provides a versatile, panel-agnostic framework to facilitate scalable biomarker discovery and precision oncology.

q-bio.QM↗

arXiv2026

TRIDENT: Tri-Modal Molecular Representation Learning with Taxonomic Annotations and Local Correspondence

Molecular property prediction aims to learn representations that map chemical structures to functional properties. While multimodal learning has emerged as a powerful paradigm to learn molecular representations, prior works have largely overlooked textual and taxonomic information of molecules for representation learning. We introduce TRIDENT, a novel framework that integrates molecular SMILES, textual descriptions, and taxonomic functional annotations to learn rich molecular representations. To achieve this, we curate a comprehensive dataset of molecule-text pairs with structured, multi-level functional annotations. Instead of relying on conventional contrastive loss, TRIDENT employs a volume-based alignment objective to jointly align tri-modal features at the global level, enabling soft, geometry-aware alignment across modalities. Additionally, TRIDENT introduces a novel local alignment objective that captures detailed relationships between molecular substructures and their corresponding sub-textual descriptions. A momentum-based mechanism dynamically balances global and local alignment, enabling the model to learn both broad functional semantics and fine-grained structure-function mappings. TRIDENT achieves state-of-the-art performance on 11 downstream tasks, demonstrating the value of combining SMILES, textual, and taxonomic functional annotations for molecular property prediction.

cs.LG↗

arXiv2026

Breaking the Correlation Plateau: On the Optimization and Capacity Limits of Attention-Based Regressors

Attention-based regression models are often trained by jointly optimizing Mean Squared Error (MSE) loss and Pearson correlation coefficient (PCC) loss, emphasizing the magnitude of errors and the order or shape of targets, respectively. A common but poorly understood phenomenon during training is the PCC plateau: PCC stops improving early in training, even as MSE continues to decrease. We provide the first rigorous theoretical analysis of this behavior, revealing fundamental limitations in both optimization dynamics and model capacity. First, in regard to the flattened PCC curve, we uncover a critical conflict where lowering MSE (magnitude matching) can paradoxically suppress the PCC gradient (shape matching). This issue is exacerbated by the softmax attention mechanism, particularly when the data to be aggregated is highly homogeneous. Second, we identify a limitation in the model capacity: we derived a PCC improvement limit for any convex aggregator (including the softmax attention), showing that the convex hull of the inputs strictly bounds the achievable PCC gain. We demonstrate that data homogeneity intensifies both limitations. Motivated by these insights, we propose the Extrapolative Correlation Attention (ECA), which incorporates novel, theoretically-motivated mechanisms to improve the PCC optimization and extrapolate beyond the convex hull. Across diverse benchmarks, including challenging homogeneous data setting, ECA consistently breaks the PCC plateau, achieving significant improvements in correlation without compromising MSE performance.

cs.LG↗

arXiv2026

Histopathology-centered Computational Evolution of Spatial Omics: Integration, Mapping, and Foundation Models

Spatial omics (SO) technologies enable spatially resolved molecular profiling, while hematoxylin and eosin (H&E) imaging remains the gold standard for morphological assessment in clinical pathology. Recent computational advances increasingly place H&E images at the center of SO analysis, bridging morphology with transcriptomic, proteomic, and other spatial molecular modalities, and pushing resolution toward the single-cell level. In this survey, we systematically review the computational evolution of SO from a histopathology-centered perspective and organize existing methods into three paradigms: integration, which jointly models paired multimodal data; mapping, which infers molecular profiles from H&E images; and foundation models, which learn generalizable representations from large-scale spatial datasets. We analyze how the role of H&E images evolves across these paradigms from spatial context to predictive anchor and ultimately to representation backbone in response to practical constraints such as limited paired data and increasing resolution demands. We further summarize actionable modeling directions enabled by current architectures and delineate persistent gaps driven by data, biology, and technology that are unlikely to be resolved by model design alone. Together, this survey provides a histopathology-centered roadmap for developing and applying computational frameworks in SO.

q-bio.GN↗

arXiv2025

GenePheno: Interpretable Gene Knockout-Induced Phenotype Abnormality Prediction from Gene Sequences

Exploring how genetic sequences shape phenotypes is a fundamental challenge in biology and a key step toward scalable, hypothesis-driven experimentation. The task is complicated by the large modality gap between sequences and phenotypes, as well as the pleiotropic nature of gene-phenotype relationships. Existing sequence-based efforts focus on the degree to which variants of specific genes alter a limited set of phenotypes, while general gene knockout induced phenotype abnormality prediction methods heavily rely on curated genetic information as inputs, which limits scalability and generalizability. As a result, the task of broadly predicting the presence of multiple phenotype abnormalities under gene knockout directly from gene sequences remains underexplored. We introduce GenePheno, the first interpretable multi-label prediction framework that predicts knockout induced phenotypic abnormalities from gene sequences. GenePheno employs a contrastive multi-label learning objective that captures inter-phenotype correlations, complemented by an exclusive regularization that enforces biological consistency. It further incorporates a gene function bottleneck layer, offering human interpretable concepts that reflect functional mechanisms behind phenotype formation. To support progress in this area, we curate four datasets with canonical gene sequences as input and multi-label phenotypic abnormalities induced by gene knockouts as targets. Across these datasets, GenePheno achieves state-of-the-art gene-centric $F_{\text{max}}$ and phenotype-centric AUC, and case studies demonstrate its ability to reveal gene functional mechanisms.

cs.LG↗

arXiv2025

DICE: Discrete Inversion Enabling Controllable Editing for Multinomial Diffusion and Masked Generative Models

Discrete diffusion models have achieved success in tasks like image generation and masked language modeling but face limitations in controlled content editing. We introduce DICE (Discrete Inversion for Controllable Editing), the first approach to enable precise inversion for discrete diffusion models, including multinomial diffusion and masked generative models. By recording noise sequences and masking patterns during the reverse diffusion process, DICE enables accurate reconstruction and flexible editing of discrete data without the need for predefined masks or attention manipulation. We demonstrate the effectiveness of DICE across both image and text domains, evaluating it on models such as VQ-Diffusion, Paella, and RoBERTa. Our results show that DICE preserves high data fidelity while enhancing editing capabilities, offering new opportunities for fine-grained content manipulation in discrete spaces.

cs.CV↗

arXiv2025

GRAM-DTI: adaptive multimodal representation learning for drug target interaction prediction

Drug target interaction (DTI) prediction is a cornerstone of computational drug discovery, enabling rational design, repurposing, and mechanistic insights. While deep learning has advanced DTI modeling, existing approaches primarily rely on SMILES protein pairs and fail to exploit the rich multimodal information available for small molecules and proteins. We introduce GRAMDTI, a pretraining framework that integrates multimodal molecular and protein inputs into unified representations. GRAMDTI extends volume based contrastive learning to four modalities, capturing higher-order semantic alignment beyond conventional pairwise approaches. To handle modality informativeness, we propose adaptive modality dropout, dynamically regulating each modality's contribution during pre-training. Additionally, IC50 activity measurements, when available, are incorporated as weak supervision to ground representations in biologically meaningful interaction strengths. Experiments on four publicly available datasets demonstrate that GRAMDTI consistently outperforms state of the art baselines. Our results highlight the benefits of higher order multimodal alignment, adaptive modality utilization, and auxiliary supervision for robust and generalizable DTI prediction.

cs.LG↗

arXiv2025

AdaRing: Towards Ultra-Light Vision-Language Adaptation via Cross-Layer Tensor Ring Decomposition

Adapter-based fine-tuning has gained remarkable attention in adapting large pre-trained vision language models (VLMs) for a wide range of downstream tasks efficiently. In this paradigm, only the inserted adapters are fine-tuned, without the need for training the original VLM backbone. Existing works scale adapters by integrating them into every layer of VLMs to increase the capacity of adapters. However, these methods face two primary limitations: 1) limited compression rate due to ignoring cross-layer redundancy, and 2) limited representational capacity across homogeneous adapters. In this paper, we propose a novel vision-language fine-tuning framework based on cross-layer tensor ring decomposition (TRD) with the integration and collaboration of diverse adapters, called AdaRing, achieving ultra-light parameter-efficient adaptation of VLMs on various tasks. To remove the high redundancy that exists among adapters across layers, we exploit the tensor-level low-rankness to formulate adapters as layer-shared tensor cores and layer-specific slices. Moreover, guided by generalization-aware fine-tuning, diverse rank-driven adapters cooperate to handle tasks that require different representations. Our experiments show that the proposed AdaRing achieves the state-of-the-art performance while reducing average training parameters by 90%.

cs.CV↗