Graph Pseudotime Analysis and Neural Stochastic Differential Equations for Analyzing Retinal Degeneration Dynamics and Beyond

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.

Machine Learning-Based Prediction of Key Genes Correlated to the Subretinal Lesion Severity in a Mouse Model of Age-Related Macular Degeneration

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.

Spatial--spectral FFPNet: Attention-Based Pyramid Network for Segmentation and Classification of Remote Sensing Images

We consider the problem of segmentation and classification of high-resolution and hyperspectral remote sensing images. Unlike conventional natural (RGB) images, the inherent large scale and complex structures of remote sensing images pose major challenges such as spatial object distribution diversity and spectral information extraction when existing models are directly applied for image classification. In this study, we develop an attention-based pyramid network for segmentation and classification of remote sensing datasets. Attention mechanisms are used to develop the following modules: i) a novel and robust attention-based multi-scale fusion method effectively fuses useful spatial or spectral information at different and same scales; ii) a region pyramid attention mechanism using region-based attention addresses the target geometric size diversity in large-scale remote sensing images; and iii cross-scale attention} in our adaptive atrous spatial pyramid pooling network adapts to varied contents in a feature-embedded space. Different forms of feature fusion pyramid frameworks are established by combining these attention-based modules. First, a novel segmentation framework, called the heavy-weight spatial feature fusion pyramid network (FFPNet), is proposed to address the spatial problem of high-resolution remote sensing images. Second, an end-to-end spatial--spectral FFPNet is presented for classifying hyperspectral images. Experiments conducted on ISPRS Vaihingen and ISPRS Potsdam high-resolution datasets demonstrate the competitive segmentation accuracy achieved by the proposed heavy-weight spatial FFPNet. Furthermore, experiments on the Indian Pines and the University of Pavia hyperspectral datasets indicate that the proposed spatial--spectral FFPNet outperforms the current state-of-the-art methods in hyperspectral image classification.