arXiv subjects

Zihao Luo

Publications and source records attributed to Zihao Luo.

8 recordsLinked to original sources

arXiv2026

Bi-TEAM: A Unified Cross-Scale Representation Learning Framework for Chemically Modified Biomolecules

Representation learning for protein biochemical space faces a difficult trade-off: protein language models excel at capturing long-range biological semantics but often miss fine-grained chemical details. Conversely, chemical language models encode atomic information but lack broader sequence context. To address this, we introduce Bi-TEAM (Bi-gated Residual Space Modification), a general framework that injects localized chemical variation into global protein contexts. By ensuring robustness against perturbations such as non-canonical amino acids, post-translational modifications (PTMs), and topological constraints, Bi-TEAM uncovers functional chemical dependencies often missed by evolutionary baselines. Mechanistically, Bi-TEAM maps non-canonical residues to their natural counterparts and injects atomic-level data via a bi-gated residual fusion mechanism. Crucially, this process uses modification-aware prompts to ensure that local structural changes influence global functional representations without requiring alphabet expansion. We evaluated Bi-TEAM on ten datasets spanning chemically modified peptides, PTMs, and natural proteins. The model consistently outperformed state-of-the-art baselines, achieving up to a 66 percent improvement in Matthews correlation coefficient (MCC) on scaffold-similarity splits and a 350 percent increase in hemolysis prediction accuracy. Furthermore, when deployed as an oracle for generative modeling, Bi-TEAM nearly quadrupled the success rate for designing cell-penetrating cyclic peptides. By unifying biological semantics with chemical precision, Bi-TEAM provides a versatile foundation for machine learning driven exploration of peptide and protein biochemical space.

q-bio.BM↗

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↗

arXiv2026

A Field-Weighted model for Surface Layer Characterization using Single Channel Intensity Interrogation SPR

To address the difficulty of characterizing the surface layer rigorously, especially the thickness and refractive index (RI) in surface plasmon resonance (SPR) technology, we propose a field-weighted analysis method. This approach enables simultaneous quantitative determination of RI for the bulk solution and the surface layer. This study utilizes the aluminum-based Kretschmann structure with the intensity interrogation technique. We construct the field-weighted model governed by the evanescent field penetration depth to decompose the SPR reflected intensity into the bulk and surface responses. Experiments are conducted using bovine serum albumin (BSA) solution to form a surface adsorbed protein layer, and different concentrations of BSA are tested. Results show that the separated surface response fits well with the Langmuir formula, representing a significant improvement over the untreated SPR signal. The bulk and surface responses are then incorporated into the field-weighted model to determine the RI values of the bulk BSA solution and the surface adsorbed BSA layer at various concentrations. The experimental results of BSA solution match the Abbe refractometer measurements with a maximum error 0.0004 in RI, while the results of the adsorbed BSA layer, both the RI and thickness, aligned well with reported parameters for a single BSA layer. This method eliminates the stage rotation in the common angular interrogation SPR technique and complicated optical design and nano-fabrication in the nano-optics sensing schemes, making it suitable for compact, low-cost SPR platforms for practical applications needing surface layer characterization.

physics.optics↗

arXiv2025

InvCoSS: Inversion-driven Continual Self-supervised Learning in Medical Multi-modal Image Pre-training

Continual self-supervised learning (CSSL) in medical imaging trains a foundation model sequentially, alleviating the need for collecting multi-modal images for joint training and offering promising improvements in downstream performance while preserving data privacy. However, most existing methods still rely on replaying data from previous stages to prevent catastrophic forgetting, which compromises privacy and limits their applicability in real-world scenarios where data transfer across sites is often restricted. In this work, we propose InvCoSS, an inversion-driven continual self-supervised learning framework for medical multi-modal image pre-training. Specifically, after training on a previous task, InvCoSS inverts the pre-trained self-supervised model to generate synthetic images that approximate the original training distribution. These synthetic images are then combined with data from the new task for joint optimization, which effectively mitigates catastrophic forgetting while strictly adhering to the constraint of no access to previous real data. Furthermore, to improve the fidelity of synthetic images, we introduce a novel InvUNet with a multi-scale fusion architecture to restore both high- and low-frequency components of the inverted images. To enhance diversity and prevent mode collapse, we design a repulsive representation-learning mechanism that encourages a diverse feature space for synthetic images without class guidance. Extensive experiments across nine downstream tasks validate the effectiveness of InvCoSS, achieving performance comparable to or even superior to prior data-replay methods while significantly reducing storage requirements and eliminating data privacy constraints.

cs.CV↗

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

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↗

arXiv2024

An Uncertainty-guided Tiered Self-training Framework for Active Source-free Domain Adaptation in Prostate Segmentation

Deep learning models have exhibited remarkable efficacy in accurately delineating the prostate for diagnosis and treatment of prostate diseases, but challenges persist in achieving robust generalization across different medical centers. Source-free Domain Adaptation (SFDA) is a promising technique to adapt deep segmentation models to address privacy and security concerns while reducing domain shifts between source and target domains. However, recent literature indicates that the performance of SFDA remains far from satisfactory due to unpredictable domain gaps. Annotating a few target domain samples is acceptable, as it can lead to significant performance improvement with a low annotation cost. Nevertheless, due to extremely limited annotation budgets, careful consideration is needed in selecting samples for annotation. Inspired by this, our goal is to develop Active Source-free Domain Adaptation (ASFDA) for medical image segmentation. Specifically, we propose a novel Uncertainty-guided Tiered Self-training (UGTST) framework, consisting of efficient active sample selection via entropy-based primary local peak filtering to aggregate global uncertainty and diversity-aware redundancy filter, coupled with a tiered self-learning strategy, achieves stable domain adaptation. Experimental results on cross-center prostate MRI segmentation datasets revealed that our method yielded marked advancements, with a mere 5% annotation, exhibiting an average Dice score enhancement of 9.78% and 7.58% in two target domains compared with state-of-the-art methods, on par with fully supervised learning. Code is available at:https://github.com/HiLab-git/UGTST

cs.CV↗

arXiv2024

Privacy-Preserving Low-Rank Adaptation against Membership Inference Attacks for Latent Diffusion Models

Low-rank adaptation (LoRA) is an efficient strategy for adapting latent diffusion models (LDMs) on a private dataset to generate specific images by minimizing the adaptation loss. However, the LoRA-adapted LDMs are vulnerable to membership inference (MI) attacks that can judge whether a particular data point belongs to the private dataset, thus leading to the privacy leakage. To defend against MI attacks, we first propose a straightforward solution: Membership-Privacy-preserving LoRA (MP-LoRA). MP-LoRA is formulated as a min-max optimization problem where a proxy attack model is trained by maximizing its MI gain while the LDM is adapted by minimizing the sum of the adaptation loss and the MI gain of the proxy attack model. However, we empirically find that MP-LoRA has the issue of unstable optimization, and theoretically analyze that the potential reason is the unconstrained local smoothness, which impedes the privacy-preserving adaptation. To mitigate this issue, we further propose a Stable Membership-Privacy-preserving LoRA (SMP-LoRA) that adapts the LDM by minimizing the ratio of the adaptation loss to the MI gain. Besides, we theoretically prove that the local smoothness of SMP-LoRA can be constrained by the gradient norm, leading to improved convergence. Our experimental results corroborate that SMP-LoRA can indeed defend against MI attacks and generate high-quality images. Our Code is available at \url{https://github.com/WilliamLUO0/StablePrivateLoRA}.

cs.LG↗