Zhuowei Yu

Kuan Yan, Yue Zeng, Dai Shi et al.

Age-related macular degeneration (AMD) is a major cause of blindness in older adults, severely affecting vision and quality of life. Despite advances in understanding AMD, the molecular factors driving the severity of subretinal scarring (fibrosis) remain elusive, hampering the development of effective therapies. This study introduces a machine learning-based framework to predict key genes that are strongly correlated with lesion severity and to identify potential therapeutic targets to prevent subretinal fibrosis in AMD. Using an original RNA sequencing (RNA-seq) dataset from the diseased retinas of JR5558 mice, we developed a novel and specific feature engineering technique, including pathway-based dimensionality reduction and gene-based feature expansion, to enhance prediction accuracy. Two iterative experiments were conducted by leveraging Ridge and ElasticNet regression models to assess biological relevance and gene impact. The results highlight the biological significance of several key genes and demonstrate the framework's effectiveness in identifying novel therapeutic targets. The key findings provide valuable insights for advancing drug discovery efforts and improving treatment strategies for AMD, with the potential to enhance patient outcomes by targeting the underlying genetic mechanisms of subretinal lesion development.

Zhuokun Chen, Jugang Fan, Zhuowei Yu et al.

Visual autoregressive modeling, based on the next-scale prediction paradigm, exhibits notable advantages in image quality and model scalability over traditional autoregressive and diffusion models. It generates images by progressively refining resolution across multiple stages. However, the computational overhead in high-resolution stages remains a critical challenge due to the substantial number of tokens involved. In this paper, we introduce SparseVAR, a plug-and-play acceleration framework for next-scale prediction that dynamically excludes low-frequency tokens during inference without requiring additional training. Our approach is motivated by the observation that tokens in low-frequency regions have a negligible impact on image quality in high-resolution stages and exhibit strong similarity with neighboring tokens. Additionally, we observe that different blocks in the next-scale prediction model focus on distinct regions, with some concentrating on high-frequency areas. SparseVAR leverages these insights by employing lightweight MSE-based metrics to identify low-frequency tokens while preserving the fidelity of excluded regions through a small set of uniformly sampled anchor tokens. By significantly reducing the computational cost while maintaining high image generation quality, SparseVAR achieves notable acceleration in both HART and Infinity. Specifically, SparseVAR achieves up to a 2 times speedup with minimal quality degradation in Infinity-2B.

Dai Shi, Kuan Yan, Lequan Lin et al.

Understanding disease progression at the molecular pathway level usually requires capturing both structural dependencies between pathways and the temporal dynamics of disease evolution. In this work, we solve the former challenge by developing a biologically informed graph-forming method to efficiently construct pathway graphs for subjects from our newly curated JR5558 mouse transcriptomics dataset. We then develop Graph-level Pseudotime Analysis (GPA) to infer graph-level trajectories that reveal how disease progresses at the population level, rather than in individual subjects. Based on the trajectories estimated by GPA, we identify the most sensitive pathways that drive disease stage transitions. In addition, we measure changes in pathway features using neural stochastic differential equations (SDEs), which enables us to formally define and compute pathway stability and disease bifurcation points (points of no return), two fundamental problems in disease progression research. We further extend our theory to the case when pathways can interact with each other, enabling a more comprehensive and multi-faceted characterization of disease phenotypes. The comprehensive experimental results demonstrate the effectiveness of our framework in reconstructing the dynamics of the pathway, identifying critical transitions, and providing novel insights into the mechanistic understanding of disease evolution.