Abstract B006: Using TAPESTRY to interactively explore tumor-specific alternative splicing in pediatric tumors

Abstract

Alternative splicing (AS) is a major contributor to molecular diversity in pediatric central nervous system (CNS) tumors, with a median of approximately 130,000 splicing events observed per tumor. Furthermore, AS can lead to production of tumor-specific proteoforms that may serve as promising targets for immunotherapy. The scale and complexity of RNA splicing datasets make them difficult to interpret, particularly for researchers without computational expertise. This gap limits the ability of the broader pediatric neuro-oncology community to effectively leverage splicing data for clinical translation. We developed TAPESTRY (Tumor Alternative PEdiatric Splicing visualizaTion and queRYing) to support direct exploration of tumor-enriched splice junction data by non-computational users. TAPESTRY integrates AS data from 1,916 pediatric CNS tumors from the Open Pediatric Cancer Project alongside normal brain RNA-seq spanning fetal to young adult stages (Evo-Devo atlas, pediatric normal brains, and GTEx <40 years; total N = 250). The platform consists of a user-friendly front-end interface connected to a backend database through an API, allowing query and retrieval of large-scale datasets. Multiple filtering options are available for splice junction prioritization, and notably, we have integrated matched and Dependency map (DEPMAP) cell lines to support the selection of appropriate in vitro models that recapitulate splicing patterns. TAPESTRY currently provides an interactive visualization suite that displays junction expression across solid tumors, normal brain, and derived cell lines, enabling rapid assessment of tumor specificity and cell line selectivity. Additional views highlight junction context in gene models and junction-level expression across genes of interest. TAPESTRY is designed to accelerate translational discovery by enabling domain experts to directly interrogate pediatric CNS tumor splicing events of interest, leading to faster prioritization, preclinical testing, and ultimately translation to the clinic. TAPESTRY is an actively developing platform, and future work seeks to ingest additional tumor and reference normal data sets (e.g., neuroblastoma, developmental and non-brain GTEx samples) and enable additional features including visualization of splice junction clinical and molecular correlates (e.g., gene and protein expression, survival).