arXiv subjects

Zijun Gao

Publications and source records attributed to Zijun Gao.

At least 37 records · Page 2Linked to original sources

arXiv2026

A Decade-Long Increasing Mid-Infrared Luminosity in Galaxy NGC6447: a Turning-On Candidate of Active Galactic Nucleus

It is widely expected that the obscured accretion stage can be the initial turning-on stage of active galactic nuclei from quiescent galaxies. We present mid-infrared light curves of NGC 6447 in 3.5$μ$m and 4.6 $μ$m bands observed by WISE/NEOWISE, which show an almost monotonic increasing trend of 1.2 mag over 14 years. The optical light curve from ASAS-SN during the same period is consistent with a constant showing no variability. The mid-infrared color evolution shows that the galaxy transitioned into an active galactic nucleus (AGN) in 2018. The SPHEREx spectrum reveals an increasing continuum resembling warm to hot dust emission from an AGN. NuSTAR detected an X-ray source with a 2-30 keV luminosity of $8.4\times10^{41}$ ergs/s at the lower boundary of AGN X-ray emission range, and a factor of >7 variability in one year compared to the Swift upper limit. NGC 6447 was classified as a quiescent galaxy in the literature. The multi-wavelength timing and spectral properties of NGC 6447 are consistent with the expected AGN turning on event, where the obscuring material around the AGN central engine is gradually dispersed, revealing the central engine. This example shows that long-term infrared variability can be a powerful tool to find similar sources. Based on the sample selection statistics, we estimate the duration of the episodes of AGN accretion (duty cycle) signified by the turning-on event as $10^4$-$10^6$ yr.

astro-ph.GA↗

arXiv2026

Statistical Inference in Causal Partial Identification with Smooth Densities

Many causal quantities are only partially identifiable due to the inherent missingness of potential outcomes, and the associated partial identification (PI) sets can be obtained by solving an optimal transport (OT) problem. Covariates often provide additional information about the potential outcomes and thus yield tighter PI sets, which can be obtained via conditional optimal transport (COT). However, COT-based PI set estimators are susceptible to the curse of dimensionality in the covariates and outcomes, which precludes the asymptotic normality and hinders statistical inference. In this paper, we exploit smoothness in the marginal densities of covariates and potential outcomes and develop a wavelet-based primal method for COT with multivariate outcomes and covariates. Moreover, for quadratic cost functions, we establish a stability result for COT and prove asymptotic normality of the proposed estimator. This characterization of the asymptotic distribution enables valid statistical inference for the partial identification set. Empirically, we validate the estimation and inference performance of our approach through numerical experiments in comparison with existing benchmarks.

math.ST↗

arXiv2026

Causal Partial Identification via Conditional Optimal Transport

We study the estimation of causal estimand involving the joint distribution of treatment and control outcomes for a single unit. In typical causal inference settings, it is impossible to observe both outcomes simultaneously, which places our estimation within the domain of partial identification (PI). Pre-treatment covariates can substantially reduce estimation uncertainty by shrinking the partially identified set. Recent work has shown that covariate-assisted PI sets can be characterized through conditional optimal transport (COT) problems. However, finite-sample estimation of COT poses significant challenges, primarily because the COT functional is discontinuous under the weak topology, rendering the direct plug-in estimator inconsistent. To address this issue, existing literature relies on relaxations or indirect methods involving the estimation of non-parametric nuisance statistics. In this work, we demonstrate the continuity of the COT functional under a stronger topology induced by the adapted Wasserstein distance. Leveraging this result, we propose a direct, consistent, non-parametric estimator for COT value that avoids nuisance parameter estimation. We derive the convergence rate for our estimator and validate its effectiveness through comprehensive simulations, demonstrating its improved performance compared to existing approaches.

stat.ME↗

arXiv2026

SegRap2025: A Benchmark of Gross Tumor Volume and Lymph Node Clinical Target Volume Segmentation for Radiotherapy Planning of Nasopharyngeal Carcinoma

Accurate delineation of Gross Tumor Volume (GTV), Lymph Node Clinical Target Volume (LN CTV), and Organ-at-Risk (OAR) from Computed Tomography (CT) scans is essential for precise radiotherapy planning in Nasopharyngeal Carcinoma (NPC). Building upon SegRap2023, which focused on OAR and GTV segmentation using single-center paired non-contrast CT (ncCT) and contrast-enhanced CT (ceCT) scans, the SegRap2025 challenge aims to enhance the generalizability and robustness of segmentation models across imaging centers and modalities. SegRap2025 comprises two tasks: Task01 addresses GTV segmentation using paired CT from the SegRap2023 dataset, with an additional external testing set to evaluate cross-center generalization, and Task02 focuses on LN CTV segmentation using multi-center training data and an unseen external testing set, where each case contains paired CT scans or a single modality, emphasizing both cross-center and cross-modality robustness. This paper presents the challenge setup and provides a comprehensive analysis of the solutions submitted by ten participating teams. For GTV segmentation task, the top-performing models achieved average Dice Similarity Coefficient (DSC) of 74.61% and 56.79% on the internal and external testing cohorts, respectively. For LN CTV segmentation task, the highest average DSC values reached 60.24%, 60.50%, and 57.23% on paired CT, ceCT-only, and ncCT-only subsets, respectively. SegRap2025 establishes a large-scale multi-center, multi-modality benchmark for evaluating the generalization and robustness in radiotherapy target segmentation, providing valuable insights toward clinically applicable automated radiotherapy planning systems. The benchmark is available at: https://hilab-git.github.io/SegRap2025_Challenge.

eess.IV↗

arXiv2025

CONFIDE: Hallucination Assessment for Reliable Biomolecular Structure Prediction and Design

Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration within the protein folding energy landscape. We present CODE (Chain of Diffusion Embeddings), a self evaluating metric empirically found to quantify topological frustration directly from the latent diffusion embeddings of the AlphaFold3 series of structure predictors in a fully unsupervised manner. Integrating this with pLDDT, we propose CONFIDE, a unified evaluation framework that combines energetic and topological perspectives to improve the reliability of AlphaFold3 and related models. CODE strongly correlates with protein folding rates driven by topological frustration, achieving a correlation of 0.82 compared to pLDDT's 0.33 (a relative improvement of 148\%). CONFIDE significantly enhances the reliability of quality evaluation in molecular glue structure prediction benchmarks, achieving a Spearman correlation of 0.73 with RMSD, compared to pLDDT's correlation of 0.42, a relative improvement of 73.8\%. Beyond quality assessment, our approach applies to diverse drug design tasks, including all-atom binder design, enzymatic active site mapping, mutation induced binding affinity prediction, nucleic acid aptamer screening, and flexible protein modeling. By combining data driven embeddings with theoretical insight, CODE and CONFIDE outperform existing metrics across a wide range of biomolecular systems, offering robust and versatile tools to refine structure predictions, advance structural biology, and accelerate drug discovery.

q-bio.BM↗

arXiv2025

Learning the PTM Code through a Coarse-to-Fine, Mechanism-Aware Framework

Post-translational modifications (PTMs) form a combinatorial "code" that regulates protein function, yet deciphering this code - linking modified sites to their catalytic enzymes - remains a central unsolved problem in understanding cellular signaling and disease. We introduce COMPASS-PTM, a mechanism-aware, coarse-to-fine learning framework that unifies residue-level PTM profiling with enzyme-substrate assignment. COMPASS-PTM integrates evolutionary representations from protein language models with physicochemical priors and a crosstalk-aware prompting mechanism that explicitly models inter-PTM dependencies. This design allows the model to learn biologically coherent patterns of cooperative and antagonistic modifications while addressing the dual long-tail distribution of PTM data. Across multiple proteome-scale benchmarks, COMPASS-PTM establishes new state-of-the-art performance, including a 122% relative F1 improvement in multi-label site prediction and a 54% gain in zero-shot enzyme assignment. Beyond accuracy, the model demonstrates interpretable generalization, recovering canonical kinase motifs and predicting disease-associated PTM rewiring caused by missense variants. By bridging statistical learning with biochemical mechanism, COMPASS-PTM unifies site-level and enzyme-level prediction into a single framework that learns the grammar underlying protein regulation and signaling.

cs.CE↗

arXiv2025

MUSE: Multi-Treatment Experiment Design for Winner Selection and Effect Estimation

We study the design of experiments with multiple treatment levels, a setting common in clinical trials and online A/B/n testing. Unlike single-treatment studies, practical analyses of multi-treatment experiments typically first select a winning treatment, and then only estimate the effect therein. Motivated by this analysis paradigm, we propose a design for MUlti-treatment experiments that jointly maximizes the accuracy of winner Selection and effect Estimation (MUSE). Explicitly, we introduce a single objective that balances selection and estimation, and determine the unit allocation to treatments and control by optimizing this objective. Theoretically, we establish finite-sample guarantees and asymptotic equivalence between our proposal and the Neyman allocation for the true optimal treatment and control. Across simulations and a real data application, our method performs favorably in both selection and estimation compared to various standard alternatives.

stat.ME↗

arXiv2025

Counterfactual explainability and analysis of variance

Existing tools for explaining complex models and systems are associational rather than causal and do not provide mechanistic understanding. We propose a new notion called counterfactual explainability for causal attribution that is motivated by the concept of genetic heritability in twin studies. Counterfactual explainability extends methods for global sensitivity analysis (including the functional analysis of variance and Sobol's indices), which assumes independent explanatory variables, to dependent explanations by using a directed acyclic graphs to describe their causal relationship. Therefore, this explanability measure directly incorporates causal mechanisms by construction. Under a comonotonicity assumption, we discuss methods for estimating counterfactual explainability and apply them to a real dataset dataset to explain income inequality by gender, race, and educational attainment.

stat.ML↗

arXiv2025

Lightweight MSA Design Advances Protein Folding From Evolutionary Embeddings

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from pretrained protein language models to generate MSAs that better support downstream folding. PLAME couples these embeddings with a conservation--diversity loss that balances agreement on conserved positions with coverage of plausible sequence variation. Beyond generation, we develop (i) an MSA selection strategy to filter high-quality candidates and (ii) a sequence-quality metric that is complementary to depth-based measures and predictive of folding gains. On AlphaFold2 low-homology/orphan benchmarks, PLAME delivers state-of-the-art improvements in structure accuracy (e.g., lDDT/TM-score), with consistent gains when paired with AlphaFold3. Ablations isolate the benefits of the selection strategy, and case studies elucidate how MSA characteristics shape AlphaFold confidence and error modes. Finally, we show PLAME functions as a lightweight adapter, enabling ESMFold to approach AlphaFold2-level accuracy while retaining ESMFold-like inference speed. PLAME thus provides a practical path to high-quality folding for proteins lacking strong evolutionary neighbors.

cs.LG↗

arXiv2025

A deep reinforcement learning platform for antibiotic discovery

Antimicrobial resistance (AMR) is projected to cause up to 10 million deaths annually by 2050, underscoring the urgent need for new antibiotics. Here we present ApexAmphion, a deep-learning framework for de novo design of antibiotics that couples a 6.4-billion-parameter protein language model with reinforcement learning. The model is first fine-tuned on curated peptide data to capture antimicrobial sequence regularities, then optimised with proximal policy optimization against a composite reward that combines predictions from a learned minimum inhibitory concentration (MIC) classifier with differentiable physicochemical objectives. In vitro evaluation of 100 designed peptides showed low MIC values (nanomolar range in some cases) for all candidates (100% hit rate). Moreover, 99 our of 100 compounds exhibited broad-spectrum antimicrobial activity against at least two clinically relevant bacteria. The lead molecules killed bacteria primarily by potently targeting the cytoplasmic membrane. By unifying generation, scoring and multi-objective optimization with deep reinforcement learning in a single pipeline, our approach rapidly produces diverse, potent candidates, offering a scalable route to peptide antibiotics and a platform for iterative steering toward potency and developability within hours.

cs.LG↗

arXiv2025

Adaptive sample splitting for randomization tests

Randomization tests are widely used to generate finite-sample valid $p$-values for causal inference on experimental data. However, when applied to subgroup analysis, these tests may lack power due to small subgroup sizes. Incorporating a shared estimator of the conditional average treatment effect (CATE) can substantially improve power across subgroups but requires sample splitting to preserve validity. To this end, we quantify each unit's contribution to estimation and testing using a certainty score, which measures how certain the unit's treatment assignment is given its covariates and outcome. We show that units with higher certainty scores are more valuable for testing but less important for CATE estimation, since their treatment assignments can be accurately imputed. Building on this insight, we propose AdaSplit, a sample splitting procedure that adaptively allocates units between estimation and testing to maximize their overall contribution across tasks. We evaluate AdaSplit through simulation studies, demonstrating that it yields more powerful randomization tests than baselines that omit CATE estimation or rely on random sample splitting. Finally, we apply AdaSplit to a blood pressure intervention trial, identifying patient subgroups with significant treatment effects.

stat.ME↗

arXiv2025

Images Speak Louder than Words: Understanding and Mitigating Bias in Vision-Language Model from a Causal Mediation Perspective

Vision-language models (VLMs) pre-trained on extensive datasets can inadvertently learn biases by correlating gender information with specific objects or scenarios. Current methods, which focus on modifying inputs and monitoring changes in the model's output probability scores, often struggle to comprehensively understand bias from the perspective of model components. We propose a framework that incorporates causal mediation analysis to measure and map the pathways of bias generation and propagation within VLMs. This approach allows us to identify the direct effects of interventions on model bias and the indirect effects of interventions on bias mediated through different model components. Our results show that image features are the primary contributors to bias, with significantly higher impacts than text features, specifically accounting for 32.57% and 12.63% of the bias in the MSCOCO and PASCAL-SENTENCE datasets, respectively. Notably, the image encoder's contribution surpasses that of the text encoder and the deep fusion encoder. Further experimentation confirms that contributions from both language and vision modalities are aligned and non-conflicting. Consequently, focusing on blurring gender representations within the image encoder, which contributes most to the model bias, reduces bias efficiently by 22.03% and 9.04% in the MSCOCO and PASCAL-SENTENCE datasets, respectively, with minimal performance loss or increased computational demands.

cs.AI↗

arXiv2025

Protein Inverse Folding From Structure Feedback

The inverse folding problem, aiming to design amino acid sequences that fold into desired three-dimensional structures, is pivotal for various biotechnological applications. Here, we introduce a novel approach leveraging Direct Preference Optimization (DPO) to fine-tune an inverse folding model using feedback from a protein folding model. Given a target protein structure, we begin by sampling candidate sequences from the inverse-folding model, then predict the three-dimensional structure of each sequence with the folding model to generate pairwise structural-preference labels. These labels are used to fine-tune the inverse-folding model under the DPO objective. Our results on the CATH 4.2 test set demonstrate that DPO fine-tuning not only improves sequence recovery of baseline models but also leads to a significant improvement in average TM-Score from 0.77 to 0.81, indicating enhanced structure similarity. Furthermore, iterative application of our DPO-based method on challenging protein structures yields substantial gains, with an average TM-Score increase of 79.5\% with regard to the baseline model. This work establishes a promising direction for enhancing protein sequence design ability from structure feedback by effectively utilizing preference optimization.

cs.LG↗

arXiv2025

Data Augmentation for Time-Series Classification: An Extensive Empirical Study and Comprehensive Survey

Data Augmentation (DA) has become a critical approach in Time Series Classification (TSC), primarily for its capacity to expand training datasets, enhance model robustness, introduce diversity, and reduce overfitting. However, the current landscape of DA in TSC is plagued with fragmented literature reviews, nebulous methodological taxonomies, inadequate evaluative measures, and a dearth of accessible and user-oriented tools. This study addresses these challenges through a comprehensive examination of DA methodologies within the TSC domain.Our research began with an extensive literature review spanning a decade, revealing significant gaps in existing surveys and necessitating a detailed analysis of over 100 scholarly articles to identify more than 60 distinct DA techniques. This rigorous review led to the development of a novel taxonomy tailored to the specific needs of DA in TSC, categorizing techniques into five primary categories: Transformation-Based, Pattern-Based, Generative, Decomposition-Based, and Automated Data Augmentation. This taxonomy is intended to guide researchers in selecting appropriate methods with greater clarity. In response to the lack of comprehensive evaluations of foundational DA techniques, we conducted a thorough empirical study, testing nearly 20 DA strategies across 15 diverse datasets representing all types within the UCR time-series repository. Using ResNet and LSTM architectures, we employed a multifaceted evaluation approach, including metrics such as Accuracy, Method Ranking, and Residual Analysis, resulting in a benchmark accuracy of 84.98 +- 16.41% in ResNet and 82.41 +- 18.71% in LSTM. Our investigation underscored the inconsistent efficacies of DA techniques, for instance, methods like RGWs and Random Permutation significantly improved model performance, whereas others, like EMD, were less effective.

cs.LG↗

arXiv2025

Tightening Causal Bounds via Covariate-Aware Optimal Transport

Causal estimands can vary significantly depending on the relationship between outcomes in treatment and control groups, potentially leading to wide partial identification (PI) intervals that impede decision making. Incorporating covariates can substantially tighten these bounds, but requires determining the range of PI over probability models consistent with the joint distributions of observed covariates and outcomes in treatment and control groups. This problem is known to be equivalent to a conditional optimal transport (COT) optimization task, which is more challenging than standard optimal transport (OT) due to the additional conditioning constraints. In this work, we study a tight relaxation of COT that effectively reduces it to standard OT, leveraging its well-established computational and theoretical foundations. Our relaxation incorporates covariate information and ensures narrower PI intervals for any value of the penalty parameter, while becoming asymptotically exact as a penalty increases to infinity. This approach preserves the benefits of covariate adjustment in PI and results in a data-driven estimator for the PI set that is easy to implement using existing OT packages. We analyze the convergence rate of our estimator and demonstrate the effectiveness of our approach through extensive simulations, highlighting its practical use and superior performance compared to existing methods.

stat.ME↗

arXiv2025

Selective randomization inference for subgroup effects with continuous biomarkers

Randomization tests are a popular method for testing causal effects in clinical trials with finite-sample validity. In the presence of heterogeneous treatment effects, it is often of interest to select a subgroup that benefits from the treatment, frequently by choosing a cutoff for a continuous biomarker. However, selecting the cutoff and testing the effect on the same data may fail to control the type I error. To address this, we propose using "self-contained" methods for selecting biomarker-based subgroups (cutoffs) and applying conditioning to construct valid randomization tests for the subgroup effect. Compared to sample-splitting-based randomization tests, our proposal is fully deterministic, uses the entire selected subgroup for inference, and is thus more powerful. Moreover, we demonstrate scenarios where our procedure achieves power comparable to a randomization test with oracle knowledge of the benefiting subgroup. In addition, our procedure is as computationally efficient as standard randomization tests. Empirically, we illustrate the effectiveness of our method on simulated datasets and the German Breast Cancer Study.

stat.ME↗

arXiv2025

SAGEPhos: Sage Bio-Coupled and Augmented Fusion for Phosphorylation Site Detection

Phosphorylation site prediction based on kinase-substrate interaction plays a vital role in understanding cellular signaling pathways and disease mechanisms. Computational methods for this task can be categorized into kinase-family-focused and individual kinase-targeted approaches. Individual kinase-targeted methods have gained prominence for their ability to explore a broader protein space and provide more precise target information for kinase inhibitors. However, most existing individual kinase-based approaches focus solely on sequence inputs, neglecting crucial structural information. To address this limitation, we introduce SAGEPhos (Structure-aware kinAse-substrate bio-coupled and bio-auGmented nEtwork for Phosphorylation site prediction), a novel framework that modifies the semantic space of main protein inputs using auxiliary inputs at two distinct modality levels. At the inter-modality level, SAGEPhos introduces a Bio-Coupled Modal Fusion method, distilling essential kinase sequence information to refine task-oriented local substrate feature space, creating a shared semantic space that captures crucial kinase-substrate interaction patterns. Within the substrate's intra-modality domain, it focuses on Bio-Augmented Fusion, emphasizing 2D local sequence information while selectively incorporating 3D spatial information from predicted structures to complement the sequence space. Moreover, to address the lack of structural information in current datasets, we contribute a new, refined phosphorylation site prediction dataset, which incorporates crucial structural elements and will serve as a new benchmark for the field. Experimental results demonstrate that SAGEPhos significantly outperforms baseline methods. We release the SAGEPhos models and code at https://github.com/ZhangJJ26/SAGEPhos.

cs.CE↗

arXiv2025

Dynamic Gradient Sparsification Training for Few-Shot Fine-tuning of CT Lymph Node Segmentation Foundation Model

Accurate lymph node (LN) segmentation is critical in radiotherapy treatment and prognosis analysis, but is limited by the need for large annotated datasets. While deep learning-based segmentation foundation models show potential in developing high-performing models with fewer samples, their medical adaptation faces LN domain-specific prior deficiencies and inefficient few-shot fine-tuning for complex clinical practices, highlighting the necessity of an LN segmentation foundation model. In this work, we annotated 36,106 visible LNs from 3,346 publicly available head-and-neck CT scans to establish a robust LN segmentation model (nnUNetv2). Building on this, we propose Dynamic Gradient Sparsification Training (DGST), a few-shot fine-tuning approach that preserves foundational knowledge while dynamically updating the most critical parameters of the LN segmentation model with few annotations. We validate it on two publicly available LN segmentation datasets: SegRap2023 and LNQ2023. The results show that DGST outperforms existing few-shot fine-tuning methods, achieving satisfactory performance with limited labeled data. We release the dataset, models and all implementations to facilitate relevant research: https://github.com/Zihaoluoh/LN-Seg-FM.

cs.CV↗