arXiv subjects

Zhaokang Liang

Publications and source records attributed to Zhaokang Liang.

4 recordsLinked to original sources

arXiv2026

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.

cs.CV↗

arXiv2026

MP2D: Constrained Monte Carlo Tree-Guided Diffusion for Multi-Objective Protein Sequence Design

Designing functional protein sequences that satisfy multiple desired properties is a core research focus of protein engineering. Prior methods struggle with inability or inefficiency when dealing with numerous, often conflicting, properties. We propose Multi-Property Protein Diffusion (MP2D), a unified framework for multi-objective protein sequence optimization that integrates conditional discrete diffusion with constrained MCTS and global iterative refinement. MP2D formulates diffusion denoising as a constrained sequential decision-making process and employs MCTS to explore diverse denoising trajectories guided by Pareto-based rewards. A global iterative refinement strategy further enables repeated remasking and re-optimization of candidate sequences, while a dynamic Pareto constraint prevents candidate bloat and maintains balanced trade-offs across objectives. We evaluate MP2D on two challenging multi-objective protein design tasks: antimicrobial peptide and protein binder optimization, involving four to five conflicting properties. Experimental results demonstrate that MP2D consistently outperforms existing multi-objective baselines, achieving robust and balanced improvements across all objectives without retraining generative models. These results highlight MP2D as a practical and scalable solution for multi-objective functional protein design.

q-bio.BM↗

arXiv2025

scPPDM: A Diffusion Model for Single-Cell Drug-Response Prediction

This paper introduces the Single-Cell Perturbation Prediction Diffusion Model (scPPDM), the first diffusion-based framework for single-cell drug-response prediction from scRNA-seq data. scPPDM couples two condition channels, pre-perturbation state and drug with dose, in a unified latent space via non-concatenative GD-Attn. During inference, factorized classifier-free guidance exposes two interpretable controls for state preservation and drug-response strength and maps dose to guidance magnitude for tunable intensity. Evaluated on the Tahoe-100M benchmark under two stringent regimes, unseen covariate combinations (UC) and unseen drugs (UD), scPPDM sets new state-of-the-art results across log fold-change recovery, delta correlations, explained variance, and DE-overlap. Representative gains include +36.11%/+34.21% on DEG logFC-Spearman/Pearson in UD over the second-best model. This control interface enables transparent what-if analyses and dose tuning, reducing experimental burden while preserving biological specificity.

q-bio.QM↗

arXiv2022

Large Quality Factor Enhancement Based on Cascaded Uniform Lithium Niobate Bichromatic Photonic Crystal Cavities

In this paper, by cascading several bichromatic photonic crystals we demonstrate that the quality factor can be much larger compared with that in an isolated cavity without increasing the total size of the device. We take lithium niobate photonic crystal as an example to illustrate that the simulated quality factor of the cascaded cavity can attain 10^5 with a 70° slant angle, which is an order of magnitude larger than that in isolated cavity. The device can be fabricated easily by current etching technique for lithium niobate. We have fabricated the proposed device experimentally including holes with 70° slant angle. This work is expected to provide guidance to the design of photonic crystal cavity with high-quality factor.

physics.optics↗