Siyuan Zhao

We present Loom, a spatial transcriptomics (ST) visual computing system to support the analysis of pseudo-temporal trajectories, comparative investigation across samples and regions of interest, and the examination of spatially structured processes within local microenvironments. ST is a molecular profiling technology that measures gene expression directly within a thin tissue section while preserving its spatial organization. For practical application-driven analyses, the ST local microenvironment data needs to be integrated with cell reference datasets and temporal simulations of cell behavior. This integration is challenging due to multi-modal registration issues and the complexity of the pseudo-temporal patterns, spatial enrichment data, and gene expression dynamics. Loom leverages a novel glyph coupled with a computational backbone to facilitate the detailed pseudo-temporal exploration of local microenvironments, cross-sample comparisons, and investigation of spatiotemporal biological mechanisms. We evaluate Loom through two case studies developed with experts in tissue pathology and oncologists and through an external usability study. The results demonstrate that Loom supports effectively the discovery of cellular transitions and spatiotemporal expression dynamics.

Dysphagia is a debilitating late effect of head and neck cancer (HNC) treatment, yet timely identification of at-risk patients remains challenging in survivorship care. Definitive assessment relies on videofluoroscopic imaging, as captured by the Dynamic Imaging Grade of Swallowing Toxicity (CTCAE-DIGEST), which, while validated, requires specialized equipment, trained personnel, and significant patient burden, limiting its routine use in surveillance. Patient-reported outcomes (PROs), by contrast, are low-cost, scalable, and easily collected at any clinical encounter, making them an attractive alternative signal for identifying patients who may warrant further evaluation. However, a clear clinical framework for translating PRO responses into actionable interventions is still evolving. In particular, uncertainty remains regarding when a patient’s self-reported symptom burden should prompt escalation of care. This study addresses this gap by formulating a single-visit PRO-clinical prediction framework and introducing a clinically interpretable two-stage stacking model to predict swallowing impairment risk using PRO responses and structured clinical variables, without requiring videofluoroscopic imaging. The proposed framework quantifies the independent contributions of patient-reported symptoms and clinical factors within a unified and interpretable risk assessment model. Our findings demonstrate that individual MDADI responses contain predictive information beyond that captured by composite or global summary scores, while interpretability analyses reveal symptom patterns and clinical risk factors associated with swallowing impairment. Together, these results support the use of structured PRO-clinical integration as a practical, imaging-free approach for dysphagia risk stratification in HNC survivorship.

The three-dimensional (3D) organization of chromatin plays a critical role in regulating gene expression and genomic processes like DNA replication, repair, and genome stability. Although these processes occur at the individual-cell level, most chromatin structure data are derived from population-averaged assays, such as Hi-C, obscuring the heterogeneity of single-cell conformations. To address this limitation, we developed a polymer physics-based modeling framework, the sequential Bayesian inference framework (sBIF), that deconvolutes bulk Hi-C data to reconstruct single-cell 3D chromatin conformations. To support a broader use of sBIF, we created ChromPolymerDB, a publicly accessible, high-resolution database of single-cell chromatin structures inferred by sBIF. The database contains  10^8 reconstructed 5 kb-resolution single cell structures, spanning over 60,000 genomic loci across 50 human cell types and experimental conditions. ChromPolymerDB features an interactive web interface with tools for 3D structural analysis and multi-omics integration. Users can explore associations between chromatin conformation and gene expression, epigenetic modifications, and regulatory elements. The platform also supports comparative analyses to identify structural changes across cell types, developmental stages, or disease contexts. ChromPolymerDB offers a unique resource for researchers studying the relationship between genome architecture and gene regulation, and for advancing comparative 3D genomics.